Hippocampal excitation-inhibition balance underlies the 5-HT2C receptor in modulating depressive behaviours

Brain, Год журнала: 2024, Номер 147(11), С. 3764 - 3779

Опубликована: Май 3, 2024

Abstract The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) activity in depression is a topic debate, and the underlying mechanisms remain largely unclear. Here, we elucidate how hippocampal excitation-inhibition (E/I) balance underlies regulatory effects 5-HT2CR depression. Molecular biological analyses showed that chronic mild stress (CMS) reduced expression hippocampus. We revealed inhibition induced depressive-like behaviours, GABA release shifted E/I towards excitation CA3 pyramidal neurons using behavioural analyses, microdialysis coupled with mass spectrometry electrophysiological recordings. Moreover, modulated neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand nNOS (CAPON) interaction by influencing intracellular Ca2+ release, as determined fibre photometry coimmunoprecipitation. Notably, disruption nNOS-CAPON specific small molecule compound ZLc-002 or AAV-CMV-CAPON-125C-GFP abolished inhibition-induced well impairment soluble N-ethylmaleimide-sensitive factor attachment protein (SNARE) complex assembly-mediated vesicle consequent imbalance. Importantly, optogenetic GABAergic prevented on depressive behaviours presence antagonist. Conclusively, our findings disclose role highlight coupling-triggered imbalance pivotal cellular event underpinning consequences inhibition.

Язык: Английский

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Advances in Human Cellular Mechanistic Understanding and Drug Discovery of Brain Organoids for Neurodegenerative Diseases

Ageing Research Reviews, Год журнала: 2024, Номер 102, С. 102517 - 102517

Опубликована: Сен. 24, 2024

Язык: Английский

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Polysaccharides from Scrophularia ningpoensis Hemsl. Improve reserpine-induced depression-like behavior by inhibiting HTR2A/HTR2C mediated AKT/GSK3β/β-catenin/CBP/BDNF signaling

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 140445 - 140445

Опубликована: Янв. 1, 2025

Язык: Английский

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Rescue of CUMS-induced HPA axis hyperfunction and hypothalamic synaptic deficits by Citrus aurantium L. cv. Daidai essential oil via the cAMP/PKA/Grin2b pathway

Journal of Ethnopharmacology, Год журнала: 2025, Номер 343, С. 119423 - 119423

Опубликована: Фев. 1, 2025

Язык: Английский

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Current Applications of Human Pluripotent Stem Cells in Neuroscience Research and Cell Transplantation Therapy for Neurological Disorders

Stem Cell Reviews and Reports, Год журнала: 2025, Номер unknown

Опубликована: Апрель 5, 2025

Язык: Английский

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Single-cell RNA sequencing reveals the intra-tumoral heterogeneity and immune microenvironment of small cell carcinoma of the ovary, hypercalcemic type

Journal of Ovarian Research, Год журнала: 2025, Номер 18(1)

Опубликована: Апрель 9, 2025

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and lethal cancer lacking effective treatment. Its genomic mutations tumor microenvironment need further exploration. We performed whole-exome sequencing or gene panel test to explore SMARCA4 mutation spectrum in SCCOHT (15 samples). Single-cell RNA was conducted on one primary lesion with matched normal ovarian tissue recurrent investigate intra-tumoral heterogeneity immune microenvironment. Multiplex immunofluorescence staining validated T infiltration PD-1 expression. 13/15 (86.7%) patients harbored mutations. The loss heterozygosity (LOH) occurred 10/15 (66.7%) patients. Cancer cells were observed tumors. divided into seven subtypes from exhibited highest stemness accompanied by high expression genes related mitosis (AURKB, CHEK2, CCNB1, WEE1), DNA repair (BRCA1, RAD51) epigenetic (EZH2, DNMT1). Immune mainly included macrophages cells. Lipid-associated tumor-associated (TAMs) while inflammatory cytokine-enriched TAMs lesion. CD4+/ CD8+ certain proportion expressed PD-1. exhibits universal LOH significant heterogeneity, suggesting potential therapeutic targets, including WEE1. Exhausted distinct TAM subsets infiltrate Targeting macrophage polarization cytokine signaling may also be promising. These findings provide insights for developing novel therapies improve outcomes SCCOHT. Not applicable.

Язык: Английский

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Functional reconstruction of the impaired cortex and motor function by hMGEOs transplantation in stroke

Biochemical and Biophysical Research Communications, Год журнала: 2023, Номер 671, С. 87 - 95

Опубликована: Июнь 3, 2023

Язык: Английский

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Human pluripotent stem cells as a translational toolkit in psychedelic research in vitro

iScience, Год журнала: 2024, Номер 27(5), С. 109631 - 109631

Опубликована: Март 28, 2024

Psychedelics, recognized for their impact on perception, are resurging as promising treatments with rapid onset mood and substance use disorders. Despite increasing evidence from clinical trials, questions persist about the cellular molecular mechanisms precise correlation treatment outcomes. Murine neurons immortalized non-neural cell lines harboring overexpressed constructs have shed light neuroplastic changes mediated by serotonin 2A receptor (5-HT2AR) primary mechanism. However, limitations exist in capturing human- disease-specific traits. Here, we discuss current accomplishments prospects incorporating human pluripotent stem cells (PSCs) to complement these models. PSCs can differentiate into various brain types, mirroring endogenous expression patterns identities recreate disease phenotypes. Brain organoids derived resemble diversity patterning, while region-specific simulate circuit-level PSC-based models hold significant promise illuminate substrates of psychedelic-induced phenotypic recovery neuropsychiatric

Язык: Английский

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Characterization of the human induced pluripotent stem cell (iPSC) SZGJMSi004-A line from a 28-year-old Han male patient with depression

Stem Cell Research, Год журнала: 2024, Номер 77, С. 103428 - 103428

Опубликована: Апрель 27, 2024

Peripheral blood mononuclear cells (PBMCs) from a 28-year-old male patient with unipolar depression were reprogrammed reprogramming factors by electroporation. The pluripotency of transgene-free induced pluripotent stem (iPSCs) was verified immunofluorescence staining for markers, and these iPSCs able to differentiate into the 3 germ layers in vitro. These also showed normal karyotypes. Thus, we believe that could be valuable models exploring underlying biological mechanism safety antidepressants through use differentiated different kinds neurons or brain organoids.

Язык: Английский

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Patient-derived induced pluripotent stem cells: Tools to advance the understanding and drug discovery in Major Depressive Disorder

Psychiatry Research, Год журнала: 2024, Номер 339, С. 116033 - 116033

Опубликована: Июль 4, 2024

Major Depressive Disorder (MDD) is a pleomorphic disease with substantial patterns of symptoms and severity mensurable deficits in several associated domains. The broad spectrum phenotypes observed patients diagnosed depressive disorders the reflection very complex where clusters biological external factors (e.g., response/processing life events, intrapsychic factors) converge mediate pathogenesis, clinical presentation/phenotypes trajectory. Patient-derived induced pluripotent stem cells (iPSCs) enable their differentiation into specialised cell types central nervous system to explore pathophysiological substrates MDD. These models may complement animal advance drug discovery identify therapeutic approaches, such as therapy, repurposing, elucidation metabolism, toxicity, mechanisms action at molecular/cellular level, pave way for precision psychiatry. Despite remarkable scientific progress made over last few decades, still poorly understood, incidence prevalence continue increase, more research needed meet demands. This review aims summarise provide critical overview conducted thus far using patient-derived iPSCs modelling psychiatric disorders, particular emphasis on

Язык: Английский

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