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1.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1318-1326, 2024 Mar.
Artículo en Chino | MEDLINE | ID: mdl-38621979

RESUMEN

In order to study the neuroprotective mechanism of cinnamaldehyde on reserpine-induced Parkinson's disease(PD) rat models, 72 male Wistar rats were randomly divided into blank group, model group, Madopar group, and cinnamaldehyde high-, medium-, and low-dose groups. Except for the blank group, the other groups were intraperitoneally injected with reserpine of 0.1 mg·kg~(-1) once every other morning, and cinnamaldehyde and Madopar solutions were gavaged every afternoon. Open field test, rotarod test, and oral chewing movement evaluation were carried out in the experiment. The brain was taken and fixed. The positive expression of dopamine receptor D1(DRD1) was detected by TSA, and the changes in neurotransmitters such as dopamine(DA) and 3,4-dihydroxyphenylacetic acid(DOPAC) in the brain were detected by enzyme-linked immunosorbent assay(ELISA). The protein and mRNA expression levels of tyrosine hydroxylase(TH) and α-synuclein(α-Syn) in substantia nigra(SN) were detected by RT-PCR and Western blot. The results showed that after the injection of reserpine, the hair color of the model group became yellow and dirty; the arrest behavior was weakened, and the body weight was reduced. The spontaneous movement and exploration behavior were reduced, and the coordination exercise ability was decreased. The number of oral chewing was increased, but the cognitive ability was decreased, and the proportion of DRD1 positive expression area in SN was decreased. The expression of TH protein and mRNA was down-regulated, and that of α-Syn protein and mRNA was up-regulated. After cinnamaldehyde intervention, it had an obvious curative effect on PD model animals. The spontaneous movement behavior, the time of staying in the rod, the time of movement, the distance of movement, and the number of standing times increased, and the number of oral chewing decreased. The proportion of DRD1 positive expression area in SN increased, and the protein and mRNA expression levels of α-Syn were down-regulated. The protein and mRNA expression levels of TH were up-regulated. In addition, the levels of DA, DOPAC, and homovanillic acid(HVA) neurotransmitters in the brain were up-regulated. This study can provide a new experimental basis for clinical treatment and prevention of PD.


Asunto(s)
Acroleína/análogos & derivados , Enfermedad de Parkinson , Ratas , Masculino , Animales , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/genética , Reserpina/efectos adversos , Reserpina/metabolismo , Ácido 3,4-Dihidroxifenilacético/metabolismo , Ratas Wistar , Sustancia Negra/metabolismo , ARN Mensajero/metabolismo , Neurotransmisores/metabolismo , Tirosina 3-Monooxigenasa/genética , Tirosina 3-Monooxigenasa/metabolismo
2.
Neurogastroenterol Motil ; 36(5): e14779, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38488234

RESUMEN

BACKGROUND: Gastric motility disorder is an increasingly common problem among people with diabetes. Neurotransmitters have been recognized as critical regulators in the process of gastric motility. Previous study has shown that herb pair huanglian-banxia (HL-BX) can improve gastric motility, but the underlying mechanism is still unclear. The aim of this study was to further investigate the role of HL-BX in modulating brain-gut neurotransmission to promote gastric motility in diabetic rats, and to explore its possible mechanism. METHODS: The diabetic rats were divided into five groups. Gastric emptying rate, intestinal propulsion rate, body weight, and average food intake were determined. Substance P (SP), 5- hydroxytryptamine (5-HT), and glucagon-like peptide -1 (GLP-1) in the serum were measured by enzyme-linked immunosorbent assay. Dopamine (DA) and norepinephrine (NE) in the brain were analyzed by high-pressure liquid chromatography with a fluorescence detector. Protein expression of the tissues in the stomach and brain was determined by Western blot. KEY RESULTS: HL-BX reduced average food intake significantly, increased body weight, and improved gastric emptying rate and intestinal propulsion rate. HL-BX administration caused a significant increase in SP, GLP-1, and 5-HT, but a significant decrease in DA and NE. Interestingly, HL-BX regulated simultaneously the different expressions of MAPK and its downstream p70S6K/S6 signaling pathway in the stomach and brain. Moreover, berberine exhibited a similar effect to HL-BX. CONCLUSIONS: These results indicated that HL-BX promoted gastric motility by regulating brain-gut neurotransmitters through the MAPK signaling pathway. HL-BX and MAPK provide a potential therapeutic option for the treatment of gastroparesis.


Asunto(s)
Diabetes Mellitus Experimental , Medicamentos Herbarios Chinos , Motilidad Gastrointestinal , Sistema de Señalización de MAP Quinasas , Animales , Masculino , Ratas , Encéfalo/metabolismo , Eje Cerebro-Intestino/fisiología , Diabetes Mellitus Experimental/metabolismo , Medicamentos Herbarios Chinos/farmacología , Motilidad Gastrointestinal/fisiología , Motilidad Gastrointestinal/efectos de los fármacos , Péptido 1 Similar al Glucagón/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/fisiología , Neurotransmisores/metabolismo
3.
Fish Shellfish Immunol ; 146: 109411, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38301813

RESUMEN

This study looked at the toxic impacts of water-born acrylamide (ACR) on Nile tilapia (Oreochromis niloticus) in terms of behaviors, growth, immune/antioxidant parameters and their regulating genes, biochemical indices, tissue architecture, and resistance to Aeromonas hydrophila. As well as the probable ameliorative effect of Chlorella vulgaris (CV) microalgae as a feed additive against ACR exposure was studied. The 96-h lethal concentration 50 of ACR was investigated and found to be 34.67 mg/L for O. niloticus. For the chronic exposure study, a total of 180 healthy O. niloticus (24.33 ± 0.03 g) were allocated into four groups in tri-replicates (15 fish/replicate), C (control) and ACR groups were fed a basal diet and exposed to 0 and 1/10 of 96-h LC50 of ACR (3.46 mg/L), respectively. ACR+ CV5 and ACR+ CV10 groups were fed basal diets with 5 % and 10 % CV supplements, respectively and exposed to 1/10 of 96-h LC50 of ACR for 60 days. After the exposure trial (60 days) the experimental groups were challenged with A. hydrophila. The findings demonstrated that ACR exposure induced growth retardation (P˂0.01) (lower final body weight, body weight gain, specific growth rate, feed intake, protein efficiency ratio, final body length, and condition factor as well as higher feed conversion ratio). A substantial decrease in the immune/antioxidant parameters (P˂0.05) (lysozyme, serum bactericidal activity %, superoxide dismutase, and reduced glutathione) and neurotransmitter (acetylcholine esterase) (P˂0.01) was noticed with ACR exposure. A substantial increase (P˂0.01) in the serum levels of hepato-renal indicators, lipid peroxidation biomarker, and cortisol was noticed as a result of ACR exposure. ACR exposure resulted in up-regulation (P˂0.05) of the pro-inflammatory cytokines and down-regulation (P˂0.05) of the antioxidant-related gene expression. Furthermore, the hepatic, renal, brain, and splenic tissues were badly affected by ACR exposure. ACR-exposed fish were more sensitive to A. hydrophila infection and recorded the lowest survival rate (P˂0.01). Feeding the ACR-exposed fish with CV diets significantly improved the growth and immune/antioxidant status, as well as modulating the hepatorenal functions, stress, and neurotransmitter level compared to the exposed-non fed fish. In addition, modulation of the pro-inflammatory and antioxidant-related gene expression was noticed by CV supplementation. Dietary CV improved the tissue architecture and increased the resistance to A. hydrophila challenge in the ACR-exposed fish. Noteworthy, the inclusion of 10 % CV produced better results than 5 %. Overall, CV diets could be added as a feed supplement in the O. niloticus diet to boost the fish's health, productivity, and resistance to A. hydrophila challenge during ACR exposure.


Asunto(s)
Chlorella vulgaris , Cíclidos , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , Animales , Antioxidantes/metabolismo , Resistencia a la Enfermedad , Dieta/veterinaria , Suplementos Dietéticos , Neurotransmisores/metabolismo , Peso Corporal , Trastornos del Crecimiento , Acrilamidas , Alimentación Animal/análisis , Enfermedades de los Peces/inducido químicamente , Infecciones por Bacterias Gramnegativas/veterinaria
4.
Brain Res ; 1824: 148676, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-37956747

RESUMEN

The olfactory bulbectomy (OBX) animal model of depression reproduces the behavioral and neurochemical changes observed in depressed patients. We assessed the therapeutic effects of the Jieyu Chufan (JYCF) capsule on OBX rats. JYCF ameliorated the hedonic and anxiety-like behavior of OBX rats and attenuated the cortical and hippocampal damage. JYCF enhanced the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2), and adiponectin (ADPN) in the cortex and hippocampus of OBX rats. JYCF also reduced cortisol levels and restored the levels of excitatory neurotransmitters, such as 5-hydroxytryptamine (5-HT), acetylcholine (ACH), and glutamic acid (Glu), in the brain tissue of OBX rats. Our results suggest that JYCF preserves the synaptic structure by increasing the levels of synaptophysin (SYN) and postsynaptic density protein 95 (PSD95) and alleviates the histological alterations of brain tissue by activating AKT/PKA-CREB-BDNF pathways, and by upregulating ADPN and FGF2 expression in OBX rats. JYCF exerts multiple therapeutic effects on depression, including modulating neurotransmitters, repairing neuronal damage, and maintaining synaptic integrity. These findings support the potential of JYCF as a novel antidepressant agent with therapeutic effects on depression and related neurological disorders.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Depresión , Humanos , Ratas , Animales , Depresión/tratamiento farmacológico , Depresión/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Neurotransmisores/metabolismo , Bulbo Olfatorio/metabolismo , Modelos Animales de Enfermedad
5.
Phytother Res ; 38(1): 231-240, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37857401

RESUMEN

To explore the antidepressant effects and targets of atractylenolide I (ATR) through a network pharmacological approach. Relevant targets of ATR and depression analyzed by network pharmacology were scored (identifying 5-HT2A targets). Through elevated plus maze, open field, tail suspension, and forced swimming tests, the behavioral changes of mice with depression (chronic unpredictable mild stress [CUMS]) were examined, and the levels of neurotransmitters including serotonin, dopamine, and norepinephrine (5-HT, DA, and NE) were determined. The binding of ATR to 5-HT2A was verified by small molecular-protein docking. ATR improved the behaviors of CUMS mice, elevated their levels of neurotransmitters 5-HT, DA, and NE, and exerted a protective effect on their nerve cell injury. After 5-HT2A knockout, ATR failed to further improve the CUMS behaviors. According to the results of small molecular-protein docking and network pharmacological analysis, ATR acted as an inhibitor by binding to 5-HT2A. ATR can improve the behaviors and modulate the neurotransmitters of CUMS mice by targeting 5-HT2A.


Asunto(s)
Depresión , Lactonas , Serotonina , Sesquiterpenos , Ratones , Animales , Depresión/tratamiento farmacológico , Depresión/metabolismo , Serotonina/metabolismo , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Neurotransmisores/metabolismo , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismo , Modelos Animales de Enfermedad , Hipocampo , Conducta Animal
6.
Biomed Pharmacother ; 170: 116012, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38113631

RESUMEN

BACKGROUND: Depression, a global neuropsychiatric disorder, brings a serious burden to patients and society as its incidence continues to rise. Berberine is one of the main compounds of a variety of Chinese herbal medicines and has been shown to have multiple pharmacological effects. However, whether berberine can exert antidepressant effects in vivo and in vitro and its related mechanisms remain to be explored. METHODS: The chronic restraint stress (CRS) method and corticosterone (CORT) were applied to simulate depression-like behavior in vivo and neuronal apoptosis in vitro, respectively. The antidepressant effects of berberine were evaluated by behavioral tests and changes in the content of monoamine neurotransmitters. Inflammatory cytokines were detected and immunofluorescence staining was used to observe the expression levels of apoptosis-related proteins. RT-qPCR and Western blot were used to examine the mRNA and protein expression (or phosphorylation) levels of biomarkers of the PI3K/AKT/CREB/BDNF signaling pathways. RESULTS: Behavioral tests and levels of neurotransmitters proved that berberine could effectively ameliorate depression-like symptoms in CRS mice. Meanwhile, the results of ELISA and immunofluorescence staining showed that berberine could alleviate inflammatory status and reduce cell apoptosis in vivo and in vitro. Moreover, the changes of the PI3K/AKT/CREB/BDNF signaling pathway induced by CRS or CORT in mouse hippocampus or HT-22 cells were significantly reversed by berberine. CONCLUSION: Our current study suggested that berberine could exert antidepressant effects in vitro and in vivo, which may be associated with the PI3K/AKT/CREB/BDNF signaling pathway.


Asunto(s)
Berberina , Proteínas Proto-Oncogénicas c-akt , Humanos , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Berberina/farmacología , Berberina/uso terapéutico , Berberina/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Transducción de Señal , Depresión/tratamiento farmacológico , Depresión/metabolismo , Corticosterona/metabolismo , Neurotransmisores/metabolismo , Hipocampo
7.
J Ethnopharmacol ; 319(Pt 3): 117355, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-37890805

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Zhi-Zi-Hou-Po decoction (ZZHP), a traditional Chinese medicine (TCM) classic recipe, has been extensively applied for the remedy of depression. However, the underlying mechanism of ZZHP hasn't been fully elucidated and it needs to be further clarified. AIM OF STUDY: The aim of the study is to uncover the mechanisms of ZZHP's effect on depression. MATERIALS AND METHODS: C57BL/6 mice were employed to establish Chronic Unpredictable Mild Stress (CUMS) models. Behavioral tests were conducted for evaluating the antidepressant effects of ZZHP. Then, the monoamine neurotransmitters in the hippocampus through High Performance Liquid Chromatography Electrochemical Detection (HPLC-ECD) were utilized to assess the effect of ZZHP on the maintenance of monoamine neurotransmitter homeostasis. Immunofluorescence staining and Golgi staining were detected to analyze the effects of ZZHP on neuroplasticity in the hippocampus. Western Blot (WB) was utilized to examine the effects of ZZHP on BDNF/TrkB/CREB pathways. Finally, behavioral tests, WB and immunofluorescence staining were repeated after TrkB receptor antagonist was added to further confirm the underlying mechanism. RESULTS: Our results shown that ZZHP attenuated depressive-like symptoms in CUMS mice. Moreover, ZZHP remarkably reversed the reduction and maintained the homeostasis of monoamine neurotransmitters in the hippocampus. Simultaneously, ZZHP protected neuronal synaptic plasticity and promoted hippocampal neurogenesis. Furthermore, ZZHP stimulated the BDNF/TrkB/CREB pathway in the hippocampus. The addition of TrkB receptor antagonist inhibited the antidepressant effects of ZZHP, suggesting that ZZHP could not work without triggering the BDNF/TrkB/CREB pathway. CONCLUSION: This study demonstrates that ZZHP can alleviate depressive-like behavior and promote hippocampal neurogenesis in CUMS mice via activating the BDNF/TrkB/CREB pathway.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Depresión , Ratones , Animales , Depresión/tratamiento farmacológico , Depresión/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Receptor trkB/metabolismo , Ratones Endogámicos C57BL , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Antidepresivos/metabolismo , Hipocampo , Neurogénesis , Neurotransmisores/metabolismo , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismo , Modelos Animales de Enfermedad
8.
Nature ; 624(7991): 333-342, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38092915

RESUMEN

The function of the mammalian brain relies upon the specification and spatial positioning of diversely specialized cell types. Yet, the molecular identities of the cell types and their positions within individual anatomical structures remain incompletely known. To construct a comprehensive atlas of cell types in each brain structure, we paired high-throughput single-nucleus RNA sequencing with Slide-seq1,2-a recently developed spatial transcriptomics method with near-cellular resolution-across the entire mouse brain. Integration of these datasets revealed the cell type composition of each neuroanatomical structure. Cell type diversity was found to be remarkably high in the midbrain, hindbrain and hypothalamus, with most clusters requiring a combination of at least three discrete gene expression markers to uniquely define them. Using these data, we developed a framework for genetically accessing each cell type, comprehensively characterized neuropeptide and neurotransmitter signalling, elucidated region-specific specializations in activity-regulated gene expression and ascertained the heritability enrichment of neurological and psychiatric phenotypes. These data, available as an online resource ( www.BrainCellData.org ), should find diverse applications across neuroscience, including the construction of new genetic tools and the prioritization of specific cell types and circuits in the study of brain diseases.


Asunto(s)
Encéfalo , Perfilación de la Expresión Génica , Animales , Ratones , Encéfalo/anatomía & histología , Encéfalo/citología , Encéfalo/metabolismo , Perfilación de la Expresión Génica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Hipotálamo/citología , Hipotálamo/metabolismo , Mesencéfalo/citología , Mesencéfalo/metabolismo , Neuropéptidos/metabolismo , Neurotransmisores/metabolismo , Fenotipo , Rombencéfalo/citología , Rombencéfalo/metabolismo , Análisis de Expresión Génica de una Sola Célula , Transcriptoma/genética
9.
Nature ; 624(7991): 355-365, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38092919

RESUMEN

Single-cell analyses parse the brain's billions of neurons into thousands of 'cell-type' clusters residing in different brain structures1. Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific cell types. Here we used epi-retro-seq2 to link single-cell epigenomes and cell types to long-distance projections for 33,034 neurons dissected from 32 different regions projecting to 24 different targets (225 source-to-target combinations) across the whole mouse brain. We highlight uses of these data for interrogating principles relating projection types to transcriptomics and epigenomics, and for addressing hypotheses about cell types and connections related to genetics. We provide an overall synthesis with 926 statistical comparisons of discriminability of neurons projecting to each target for every source. We integrate this dataset into the larger BRAIN Initiative Cell Census Network atlas, composed of millions of neurons, to link projection cell types to consensus clusters. Integration with spatial transcriptomics further assigns projection-enriched clusters to smaller source regions than the original dissections. We exemplify this by presenting in-depth analyses of projection neurons from the hypothalamus, thalamus, hindbrain, amygdala and midbrain to provide insights into properties of those cell types, including differentially expressed genes, their associated cis-regulatory elements and transcription-factor-binding motifs, and neurotransmitter use.


Asunto(s)
Encéfalo , Epigenómica , Vías Nerviosas , Neuronas , Animales , Ratones , Amígdala del Cerebelo , Encéfalo/citología , Encéfalo/metabolismo , Secuencia de Consenso , Conjuntos de Datos como Asunto , Perfilación de la Expresión Génica , Hipotálamo/citología , Mesencéfalo/citología , Vías Nerviosas/citología , Neuronas/metabolismo , Neurotransmisores/metabolismo , Secuencias Reguladoras de Ácidos Nucleicos , Rombencéfalo/citología , Análisis de la Célula Individual , Tálamo/citología , Factores de Transcripción/metabolismo
10.
PLoS One ; 18(10): e0292952, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37851674

RESUMEN

This study aimed to improve our understanding of how the hypothalamus mediates the effects of prenatal and postnatal challenges on behavior and sensitivity to stimuli. A pig model of virally initiated maternal immune activation (MIA) was used to investigate potential interactions of the prenatal challenge both with sex and with postnatal nursing withdrawal. The hypothalami of 72 females and males were profiled for the effects of MIA and nursing withdrawal using RNA-sequencing. Significant differential expression (FDR-adjusted p value < 0.05) was detected in the profile of 222 genes. Genes involved in the Gene Ontology biological process of regulation of hormone levels tended to be over-expressed in individuals exposed to both challenges relative to individuals exposed to either one challenge, and most of these genes were over-expressed in MIA females relative to males across nursing levels. Differentially expressed genes included Fshb, Ttr, Agrp, Gata3, Foxa2, Tfap2b, Gh1, En2, Cga, Msx1, and Npy. The study also found that prenatal and postnatal challenges, as well as sex, impacted the regulation of neurotransmitter activity and immune effector processes in the hypothalamus. In particular, the olfactory transduction pathway genes were over-expressed in weaned MIA males, and several transcription factors were potentially found to target the differentially expressed genes. Overall, these results highlight how multiple environmental challenges can interact and affect the molecular mechanisms of the hypothalamus, including hormonal, immune response, and neurotransmitter processes.


Asunto(s)
Neuropéptido Y , Efectos Tardíos de la Exposición Prenatal , Masculino , Embarazo , Femenino , Animales , Humanos , Porcinos , Neuropéptido Y/metabolismo , Hipotálamo/metabolismo , Vitaminas/metabolismo , Neurotransmisores/metabolismo , Efectos Tardíos de la Exposición Prenatal/metabolismo
11.
Brain Res Bull ; 203: 110768, 2023 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-37739234

RESUMEN

BACKGROUND: Stellaria dichotoma L. var. lanceolata Bge. is renowned for its efficacy in "clearing deficiency heat" and represents a significant traditional Chinese medicine (TCM) resource. Modern pharmacology has demonstrated the anti-anxiety effects of Stellaria dichotoma L. var. lanceolata Bge. polysaccharides (SDPs). SDPs are one of the active constituents of Stellaria dichotoma L. var. lanceolata Bge. This study presents the first extraction of SDPs and investigates their potential molecular mechanisms and anxiolytic effects that are not previously reported. METHODS: First, SDPs were obtained by water extraction and alcohol precipitation and analyzed for their monosaccharide composition by high performance liquid chromatography (HPLC). Male SD rats were subjected to a two-week indeterminate empty bottle stress procedure and a three-day acute restraint stress procedure, during which diazepam (DZP) (1 mg/kg) and SDPs (50, 100 and 200 mg/kg, intragastrically) were administered. A number of behavioral tests, including the elevated plus maze test (EPM), the open field test (OFT) and the light/dark box test (LDB), were used to assess the anti-anxiety potential of SDPs. Serum levels of Corticosterone (CORT) and Adrenocorticotropic hormone (ACTH), as well as the levels of Dopamine (DA) and serotonin (5-HT) found in the hippocampus and frontal cortex, were quantified using commercially available enzyme-linked immunosorbent assay (ELISA) kits. In addition, protein levels of key proteins cAMP-response element binding protein (CREB), phospho-CREB (p-CREB), brain-derived neurotrophic factor (BDNF), ERK½, p-ERK½, and GAPDH expression in rat hippocampus were measured by Western blot analysis, and modulation of the endocannabinoid system was assessed by immunohistochemistry. RESULTS: Following administration of SDPs (50, 100, 200 mg/kg) and diazepam 1 mg/kg, anxiolytic activity was exhibited through an increase in the percentage of arm opening times and arm opening time of rats in the elevated plus maze. Additionally, there was an increase in the number of times and time spent in the open field center, percentage of time spent in the open box, and shuttle times in the LDB. Furthermore, tissue levels of DA and 5-HT were increased in the hippocampus and frontal cortex of rats after treatment with SDPs. In addition, SDPs significantly decreased serum levels of CORT and ACTH in rats. SDPs also effectively regulated the phosphorylation of the extracellular regulated protein kinases (ERK) and CREB-BDNF pathway in the hippocampus. Moreover, the expression levels of CB1 and CB2 proteins were heightened due to SDPs treatment in rats. CONCLUSIONS: The study verified that SDPs alleviate anxiety in the EBS and ARS. The neuroregulatory behavior is accomplished by regulating the Monoamine neurotransmitter, HPA axis, and ECB-ERK-CREB-BDNF signaling pathway.


Asunto(s)
Ansiolíticos , Ratas , Masculino , Animales , Ansiolíticos/farmacología , Ansiolíticos/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ratas Sprague-Dawley , Proteínas Quinasas/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Serotonina/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Transducción de Señal , Hipocampo/metabolismo , Dopamina/metabolismo , Hormona Adrenocorticotrópica , Diazepam/farmacología , Neurotransmisores/metabolismo
12.
CNS Neurosci Ther ; 29(12): 3829-3841, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37309308

RESUMEN

AIMS: Transcranial focus ultrasound stimulation (tFUS) is a promising non-invasive neuromodulation technology. This study aimed to evaluate the modulatory effects of tFUS on human motor cortex (M1) excitability and explore the mechanism of neurotransmitter-related intracortical circuitry and plasticity. METHODS: Single pulse transcranial magnetic stimulation (TMS)-eliciting motor-evoked potentials (MEPs) were used to assessed M1 excitability in 10 subjects. Paired-pulse TMS was used to measure the effects of tFUS on GABA- and glutamate-related intracortical excitability and 1 H-MRS was used to assess the effects of repetitive tFUS on GABA and Glx (glutamine + glutamate) neurometabolic concentrations in the targeting region in nine subjects. RESULTS: The etFUS significantly increased M1 excitability, decreased short interval intracortical inhibition (SICI) and long interval intracortical inhibition (LICI). The itFUS significantly suppressed M1 excitability, increased SICI, LICI, and decreased intracortical facilitation (ICF). Seven times of etFUS decreased the GABA concentration (6.32%), increased the Glx concentration (12.40%), and decreased the GABA/Glx ratio measured by MRS, while itFUS increased the GABA concentration (18.59%), decreased Glx concentration (0.35%), and significantly increased GABA/Glx ratio. CONCLUSION: The findings support that tFUS with different parameters can exert excitatory and inhibitory neuromodulatory effects on the human motor cortex. We provide novel insights that tFUS change cortical excitability and plasticity by regulating excitatory-inhibition balance related to the GABAergic and glutamatergic receptor function and neurotransmitter metabolic level.


Asunto(s)
Corteza Motora , Humanos , Corteza Motora/fisiología , Inhibición Neural/fisiología , Ácido Glutámico/metabolismo , Estimulación Magnética Transcraneal , Potenciales Evocados Motores/fisiología , Ácido gamma-Aminobutírico/metabolismo , Neurotransmisores/metabolismo
13.
CNS Neurosci Ther ; 29(11): 3364-3377, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37208941

RESUMEN

BACKGROUND: General anesthesia has long been used in clinical practice, but its precise pharmacological effects on neural circuits are not fully understood. Recent investigations suggest that the sleep-wake system may play a role in the reversible loss of consciousness induced by general anesthetics. Studies in mice have shown that microinjection of dopamine receptor 1 (D1R) agonists into the nucleus accumbens (NAc) promotes recovery from isoflurane anesthesia, while microinjection of D1R antagonists has the opposite effect. Furthermore, during the induction and maintenance of sevoflurane anesthesia, there is a significant decrease in extracellular dopamine levels in the NAc, which subsequently increases during the recovery period. These findings suggest the involvement of the NAc in the regulation of general anesthesia. However, the specific role of D1R-expressing neurons in the NAc during general anesthesia and the downstream effect pathways are still not well understood. METHODS: In order to analyze the impact of sevoflurane anesthesia on NAcD1R neurons and the NAcD1R -VP pathway, this study employed calcium fiber photometry to investigate alterations in the fluorescence intensity of calcium signals in dopamine D1-receptor-expressing neurons located in the nucleus accumbens (NAcD1R neurons) and the NAcD1R -VP pathway during sevoflurane anesthesia. Subsequently, optogenetic techniques were utilized to activate or inhibit NAcD1R neurons and their synaptic terminals in the ventral pallidum (VP), aiming to elucidate the role of NAcD1R neurons and the NAcD1R -VP pathway in sevoflurane anesthesia. These experiments were supplemented with electroencephalogram (EEG) recordings and behavioral tests. Lastly, a genetically-encoded fluorescent sensor was employed to observe changes in extracellular GABA neurotransmitters in the VP during sevoflurane anesthesia. RESULTS: Our findings revealed that sevoflurane administration led to the inhibition of NAcD1R neuron population activity, as well as their connections within the ventral pallidum (VP). We also observed a reversible reduction in extracellular GABA levels in the VP during both the induction and emergence phases of sevoflurane anesthesia. Additionally, the optogenetic activation of NAcD1R neurons and their synaptic terminals in the VP resulted in a promotion of wakefulness during sevoflurane anesthesia, accompanied by a decrease in EEG slow wave activity and burst suppression rate. Conversely, the optogenetic inhibition of the NAcD1R -VP pathway exerted opposite effects. CONCLUSION: The NAcD1R -VP pathway serves as a crucial downstream pathway of NAcD1R neurons, playing a significant role in regulating arousal during sevoflurane anesthesia. Importantly, this pathway appears to be associated with the release of GABA neurotransmitters from VP cells.


Asunto(s)
Anestesia , Prosencéfalo Basal , Ratones , Animales , Núcleo Accumbens/metabolismo , Dopamina/metabolismo , Sevoflurano/farmacología , Prosencéfalo Basal/metabolismo , Calcio/metabolismo , Receptores de Dopamina D1/metabolismo , Neuronas Dopaminérgicas/metabolismo , Neurotransmisores/metabolismo , Neurotransmisores/farmacología , Ácido gamma-Aminobutírico/metabolismo
14.
Environ Sci Pollut Res Int ; 30(24): 65822-65834, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37093386

RESUMEN

Aluminium is a non-essential metal, and its accumulation in the brain is linked with potent neurotoxic action and the development of many neurological diseases. This investigation, therefore, intended to examine the antagonistic efficacy of Ficus lyrata (fiddle-leaf fig) extract (FLE) conjugated with selenium nanoparticles (FLE-SeNPs) against aluminium chloride (AlCl3)-induced hippocampal injury in rats. Rats were allocated to five groups: control, FLE, AlCl3 (100 mg/kg), AlCl3 + FLE (100 mg/kg), and AlCl3 + FLE-SeNPs (0.5 mg/kg). All agents were administered orally every day for 42 days. The result revealed that pre-treated rats with FLE-SeNPs showed markedly lower acetylcholinesterase and Na+/K+-ATPase activities in the hippocampus than those in AlCl3 group. Additionally, FLE-SeNPs counteracted the oxidant stress-mediated by AlCl3 by increasing superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione contents in rat hippocampus. Besides, the formulated nanoparticles decreased the hippocampal malondialdehyde, carbonyl protein, and nitric oxide levels of AlCl3-exposed animals. Furthermore, FLE-SeNPs attenuated neural tissue inflammation, as demonstrated by decreased interleukin-1 beta, interleukin-6, nuclear factor kappa B, and glial fibrillary acidic protein. Remarkable anti-apoptotic action was exerted by FLE-SeNPs by increasing B cell lymphoma 2 and decreasing caspase-3 and Bcl-2-associated-X protein in AlCl3-exposed rats. The abovementioned results correlated well with the hippocampal histopathological findings. Given these results, SeNPs synthesized with FLE imparted a remarkable neuroprotective action against AlCl3-induced neurotoxicity by reversing oxidative damage, neuronal inflammation, and apoptosis in exposed rats.


Asunto(s)
Ficus , Nanopartículas , Selenio , Ratas , Animales , Selenio/metabolismo , Aluminio/metabolismo , Ficus/metabolismo , Acetilcolinesterasa/metabolismo , Antioxidantes/metabolismo , Estrés Oxidativo , Neurotransmisores/metabolismo , Glutatión/metabolismo , Encéfalo/metabolismo , Inflamación/inducido químicamente , Inflamación/metabolismo , Hojas de la Planta/metabolismo
15.
Biomed Pharmacother ; 161: 114516, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36921535

RESUMEN

Nociceptive signaling responses to painful stimuli are transmitted to the central nervous system (CNS) from the afferent nerves of the periphery through a series of neurotransmitters and associated signaling mechanisms. Electroacupuncture (EA) is a pain management strategy that is widely used, with clinical evidence suggesting that a frequency of 2-10 Hz is better able to suppress neuropathic pain in comparison to higher frequencies such as 100 Hz. While EA is widely recognized as a viable approach to alleviating neuralgia, the mechanistic basis underlying such analgesic activity remains poorly understood. The present review offers an overview of current research pertaining to the mechanisms whereby EA can alleviate neuropathic pain in the CNS, with a particular focus on the serotonin/norepinephrine, endogenous opioid, endogenous cannabinoid, amino acid neurotransmitter, and purinergic pathways. Moreover, the corresponding neurotransmitters, neuromodulatory compounds, neuropeptides, and associated receptors that shape these responses are discussed. Together, this review seeks to provide a robust foundation for further studies of the EA-mediated alleviation of neuropathic pain.


Asunto(s)
Electroacupuntura , Neuralgia , Ratas , Animales , Humanos , Ratas Sprague-Dawley , Sistema Nervioso Central/metabolismo , Médula Espinal/metabolismo , Neuralgia/terapia , Neuralgia/metabolismo , Neurotransmisores/metabolismo
16.
Biomed Res Int ; 2022: 5639716, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36531656

RESUMEN

The aim of this paper was to explore the mechanism of bladder meridian massage (BMM) on anxiety in rats with chronic stress. Chronic stress induced rats to establish rat anxiety model. The sugar water preference (SPF), tail suspension time (TST), and forced swimming time (FST) of rats were measured. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and inflammatory cytokines in serum and hippocampus of rats were detected. Brain neurotransmitters (dopamine (DA), 5- hydroxytryptamine (5-HT), and norepinephrine (NE)) were detected by enzyme-linked immunosorbent assay (ELISA) kits. Immunohistochemistry and western blotting were used to detect autophagy protein expression in hippocampus of rats. BMM significantly increased SPF, decreased TST and FST, increased SOD level in serum and hippocampus, and decreased MDA level and cytokine level. BMM reversed the changes of neurotransmitters. At the same time, BMM significantly decreased autophagy protein expression in hippocampus of rats. The above results show that BMM significantly relieve anxiety induced by chronic stress in rats.


Asunto(s)
Antidepresivos , Meridianos , Ratas , Animales , Antidepresivos/farmacología , Depresión , Estrés Psicológico/complicaciones , Estrés Psicológico/terapia , Estrés Psicológico/metabolismo , Vejiga Urinaria/metabolismo , Hipocampo/metabolismo , Serotonina/metabolismo , Ansiedad/terapia , Neurotransmisores/metabolismo , Citocinas/metabolismo , Masaje , Superóxido Dismutasa/metabolismo , Modelos Animales de Enfermedad
17.
Food Chem Toxicol ; 170: 113508, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36336192

RESUMEN

The increasing prevalence of mental disorders, such as depression, is currently a serious public health concern. Microalgae are a diverse group of organisms that contain many bioactive compounds such as polyunsaturated fatty acids and polyphenols. These compounds can exhibit many health benefits such as antioxidative, anti-inflammatory, anticancer, and anti-obesity effects. In the present study, we focused on microalgal (Botryococcus terribilis) extract (ME) rich in Me-meijicoccene (MM), a novel compound. Our results showed that pretreatment of SH-SY5Y cells with ME and MM ameliorated dexamethasone (depression-causing substance)-induced cytotoxicity. The results of the tail suspension test (TST) indicated that ME (50 mg/kg) induced antidepressant-like activity in TST-stressed mice. Our microarray analysis revealed that ME upregulated neurotransmitter-related gene (neurotransmitter secretion) expression and downregulated neuroinflammatory-related gene (chemokine-mediated signaling) expression in the cerebral cortex. ME also induced an increase in neurotransmitter and brain-derived neurotrophic factor levels, and a decrease in corticosterone and pro-inflammatory cytokine levels in the serum, cerebral cortex, and hypothalamus. Altogether, our study is the first to report that 50 mg/kg ME (not 100 mg/kg) exerts antidepressant-like effects via regulating neuroinflammation and modulating neurotransmitter systems in the mouse brain, highlighting the prospects of ME in the treatment of depressive disorders of a psychosocial nature.


Asunto(s)
Microalgas , Neuroblastoma , Animales , Humanos , Ratones , Microalgas/metabolismo , Depresión/tratamiento farmacológico , Enfermedades Neuroinflamatorias , Neuroblastoma/metabolismo , Antidepresivos/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/metabolismo , Neurotransmisores/metabolismo , Hipocampo , Modelos Animales de Enfermedad
18.
Zhongguo Zhong Yao Za Zhi ; 47(17): 4691-4697, 2022 Sep.
Artículo en Chino | MEDLINE | ID: mdl-36164876

RESUMEN

To investigate the effect of Rehmanniae Radix on depression-like behavior and monoamine neurotransmitters of chronic unpredictable mild stress(CUMS) model rats. CUMS combined with isolated feeding was used to induce the depression model of rats. The depression-like behavior of rats was evaluated by sucrose preference test, open field test, and forced swim test. Hematoxylin-Eosin(HE) staining was used to investigate the pathological changes of neurons in the CA1 and CA3 area of hippocampus. Ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS) was used to detect the contents of 5-hydroxytryptamine(5-HT), 5-hydroxyindoleacetic acid(5-HIAA), dopamine(DA), 3,4-dihydroxyphenylacetic acid(DOPAC), homovanillic acid(HVA), norepinephrine(NE), and 3-methoxy-4-hydroxyphenyl glycol(MHPG) in rats. Western blot was used to detect the protein expressions of tryptophan hydroxylase 2(TPH2), serotonin transporter(SERT), and monoamine oxidase A(MAO-A) in the hippocampus of rats. Compared with the normal group, depressive-like behavior of rats was obvious in the model group. The arrangements of neurons in the CA1 and CA3 area of hippocampus were loose and disorderly. The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in the hippocampal area were decreased(P<0.01). The protein expression of TPH2 was decreased(P<0.01), but those of SERT and MAO-A were increased(P<0.01). In the Rehmanniae Radix groups with 1.8 g·kg~(-1) and 7.2 g·kg~(-1), the depression-like behavior of CUMS rats and pathological changes of neurons in CA1, CA3 area of hippocampus were improved. The protein expression of TPH2(P<0.05, P<0.01) was increased, and those of SERT and MAO-A were down-regulated(P<0.05, P<0.01). The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in hippocampus were increased(P<0.05, P<0.01). The changes in DA, DOPAC, HVA, DA/(DOPAC +HVA), NE, DHPG, and NE/DHPG were not statistically significant. The results suggested that Rehmanniae Radix improved depression-like behavior of CUMS rats, and the mechanism might be related to the regulation of synthesis, transportation, and metabolism of 5-HT neurotransmitter in the hippocampus.


Asunto(s)
Antidepresivos , Depresión , Hipocampo , Ácido Hidroxiindolacético , Rehmannia , Serotonina , Ácido 3,4-Dihidroxifenilacético/metabolismo , Ácido 3,4-Dihidroxifenilacético/farmacología , Animales , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Cromatografía Liquida , Depresión/tratamiento farmacológico , Modelos Animales de Enfermedad , Dopamina , Eosina Amarillenta-(YS)/metabolismo , Eosina Amarillenta-(YS)/farmacología , Hematoxilina/metabolismo , Hematoxilina/farmacología , Hipocampo/metabolismo , Ácido Homovanílico/metabolismo , Ácido Homovanílico/farmacología , Ácido Hidroxiindolacético/metabolismo , Metoxihidroxifenilglicol/análogos & derivados , Metoxihidroxifenilglicol/metabolismo , Metoxihidroxifenilglicol/farmacología , Monoaminooxidasa/metabolismo , Neurotransmisores/metabolismo , Norepinefrina/metabolismo , Norepinefrina/farmacología , Extractos Vegetales , Ratas , Rehmannia/química , Serotonina/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática/farmacología , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismo , Espectrometría de Masas en Tándem , Triptófano Hidroxilasa/metabolismo
19.
J Tradit Chin Med ; 42(4): 556-564, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35848972

RESUMEN

OBJECTIVE: To investigate the influence of Qihuang decoction on enteric nervous system after gastrectomy in rats. METHODS: The morphology, distribution and number of intestinal neurons in enteric nervous system (ENS) were observed by immunofluorescence labeling and confocal laser scanning microscopy. Reverse transcription-polymerase chain reaction and Western blot were used to detect the mRNA and protein expression of intestinal neurotransmitters and corresponding receptors in ENS. RESULTS: The morphology and distribution of enteric neurons in ENS were changed after gastrectomy, and these neurons in Qihuang decoction group were similar with that of sham operation group. The number of ACh and SP positive neurons, mRNA and protein expression of excitatory neurotransmitters (AChE, SP) and receptors (M3R, NK1R) were decreased after gastrectomy. And the intervention of Qihuang decoction could increase the number of ACh and SP positive neurons and promote the expression of their mRNA and protein. For vasoactive intestinal peptide (VIP) and nitric oxide synthase (NOS), the number of neurons and mRNA and protein expression of inhibitory neurotransmitters (VIP and NOS) and receptors (VIP2R) were increased after gastrectomy. And these rising indexes fall back after the intervention of Qihuang decoction. Besides, the intestinal propulsion rate in QH group was significantly increased than that in SEN and IEN group. CONCLUSIONS: These experimental results showed that after gastrectomy, early intervention with Qihuang decoction in small intestine will contribute to the postoperative recovery of enteric nervous system and intestinal propulsion rate, and consequently enhance gastrointestinal motility.


Asunto(s)
Sistema Nervioso Entérico , Animales , Sistema Nervioso Entérico/metabolismo , Gastrectomía , Neurotransmisores/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Péptido Intestinal Vasoactivo/genética , Péptido Intestinal Vasoactivo/metabolismo
20.
J Ethnopharmacol ; 295: 115302, 2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-35489661

RESUMEN

ETHNOPHARMACOLOGY RELEVANCE: Platycladus orientalis seeds are recorded in traditional Chinese medicine (TCM) formulations for modulation of mood and physical activity in "Shen Nong Ben Cao Jing" and "Compendium of Materia Medica" and so on. Recently, we identified its extracting components and looked for the potentials in treatment for depression by improving the function of monoamine neurotransmitters. AIM OF THE STUDY: We investigated the mechanism of action of the seed extracts of P. orientalis (S4) to rescue depressive behavior in a chronic, unpredicted, mild stress (CUMS)-induced model in rats. MATERIALS AND METHODS: We used ultra-fast liquid chromatography coupled with triple quadrupole-time of flight tandem mass spectrometry to analyze the chemical constituents in S4. An assay platform in zebrafish and molecular docking were used to analyze if S4 regulated rest/wake behavior and predict the biological targets which correlated with monoamine neurotransmitters. Depressive-behavior tests (body weight, sucrose preference test, tail-suspension test, forced-swimming test) were carried in the CUMS model. After behavior tests and killing, rat brains were separated into the hippocampus, frontier cortex and dorsal raphe nucleus. The main monoamine neurotransmitters and their metabolite concentrations in these three brain regions were measured by rapid resolution liquid chromatography coupled with triple quadrupole tandem mass spectrometry. RESULTS: Forty-one compounds were identified in S4, including fatty acids, terpenoids, amino acids, plant sterols and flavonoids. S4 could increase the total rest time and decrease the waking activity of zebrafish. S4 showed high correlation with adrenaline agonists, 5-hydroxytryptamine (5-HT) reuptake inhibitors and dopamine agonists. CUMS-group rats, compared with controls, had significantly decreased body weight and preference for sucrose water, whereas the immobility time in the tail-suspension test and forced-swimming test was increased. S4 could significantly rescue the increased levels of 5-HT, noradrenaline and dopamine in the prefrontal cortex and dorsal raphe nucleus. CONCLUSIONS: We demonstrated that S4 was a potential inhibitor of MAO reuptake that could rescue depression in a CUMS-model rats by restoring monoamine neurotransmitters in different encephalic regions.


Asunto(s)
Antidepresivos , Inhibidores de la Monoaminooxidasa , Animales , Antidepresivos/química , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Conducta Animal , Peso Corporal , Depresión/tratamiento farmacológico , Depresión/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Simulación del Acoplamiento Molecular , Neurotransmisores/metabolismo , Fenotipo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Serotonina/metabolismo , Estrés Psicológico/tratamiento farmacológico , Sacarosa/metabolismo , Pez Cebra
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