Altered transcriptomes, cell type proportions, and dendritic spine morphology in hippocampus of suicide decedents DOI Creative Commons
Sujan C. Das, Anton Schulmann, W. Brandon Callor

et al.

Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: 367, P. 118 - 128

Published: Aug. 25, 2024

Suicide is a manner of death resulting from complex environmental and genetic risks that affect millions people globally. Both structural functional studies identified the hippocampus as one vulnerable brain regions contributing to suicide risk. We have hippocampal tissue transcriptomes, gene ontology, cell type proportions, dendritic spine morphology in controls ( n = 28) decedents 22). In addition, transcriptomic signature iPSC-derived neuronal precursor cells (NPCs) neurons were also investigated 2) (n 2). The data revealed NPAS4 expression was downregulated while ALDH1A2 , NAAA MLXIPL expressions upregulated decedents. ontology 29 significant pathways including -associated terms "excitatory post-synaptic potential", "regulation postsynaptic membrane potential" "long-term memory" indicating alteration glutamatergic synapses deconvolution decreased excitatory neuron proportion an increased inhibitory providing evidence excitation/inhibition imbalance had dendric density hippocampus, due increase thin (relatively unstable) spines, compared controls. transcriptomes hippocampal-like NPCs 31 33 differentially expressed genes NPC neurons, respectively, Our findings will provide new insights into neuropathology suicide. • ALDH1A2, deaths. There proportions deaths each,

Language: Английский

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

Hu‐Jiang Shi,

Yi-Ren Xue,

Hua Shao

et al.

Brain, Journal Year: 2024, Volume and Issue: 147(11), P. 3764 - 3779

Published: May 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.

Language: Английский

Citations

3
Advances in Human Cellular Mechanistic Understanding and Drug Discovery of Brain Organoids for Neurodegenerative Diseases DOI
Lei Tong, Xiaoshuang Zhang,

Gaoshuang Fu

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 102, P. 102517 - 102517

Published: Sept. 24, 2024

Language: Английский

Citations

3
Polysaccharides from Scrophularia ningpoensis Hemsl. Improve reserpine-induced depression-like behavior by inhibiting HTR2A/HTR2C mediated AKT/GSK3β/β-catenin/CBP/BDNF signaling DOI
R Shen, Jianan Wang,

Yijin Zhao

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 140445 - 140445

Published: Jan. 1, 2025

Language: Английский

Citations

0
Current Applications of Human Pluripotent Stem Cells in Neuroscience Research and Cell Transplantation Therapy for Neurological Disorders DOI
Isha Verma,

Polani B. Seshagiri

Stem Cell Reviews and Reports, Journal Year: 2025, Volume and Issue: unknown

Published: April 5, 2025

Language: Английский

Citations

0
Single-cell RNA sequencing reveals the intra-tumoral heterogeneity and immune microenvironment of small cell carcinoma of the ovary, hypercalcemic type DOI Creative Commons
Yi Gao, Kewei Zheng, Haowen Tan

et al.

Journal of Ovarian Research, Journal Year: 2025, Volume and Issue: 18(1)

Published: April 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.

Language: Английский

Citations

0
Interaction between Oligodendrocytes and Interneurons in Brain Development and Related Neuropsychiatric Disorders DOI Open Access
Yingqi Liu, Jie Yuan, Yuhao Dong

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3620 - 3620

Published: March 23, 2024

A variety of neurological and psychiatric disorders have recently been shown to be highly associated with the abnormal development function oligodendrocytes (OLs) interneurons. OLs are myelin-forming cells in central nervous system (CNS), while interneurons important neural types gating excitatory neurons. These two great significance for establishment circuits, they share similar developmental origins transcriptional architectures, interact each other multiple ways during development. In this review, we compare similarities differences these cell types, providing an reference further revealing pathogenesis related brain disorders.

Language: Английский

Citations

3
Functional reconstruction of the impaired cortex and motor function by hMGEOs transplantation in stroke DOI

Shi-Ying Cao,

Mengdan Tao,

Shu-Ning Lou

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2023, Volume and Issue: 671, P. 87 - 95

Published: June 3, 2023

Language: Английский

Citations

7
Human pluripotent stem cells as a translational toolkit in psychedelic research in vitro DOI Creative Commons
José Alexandre Salerno, Stevens K. Rehen

iScience, Journal Year: 2024, Volume and Issue: 27(5), P. 109631 - 109631

Published: March 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

Language: Английский

Citations

2
Characterization of the human induced pluripotent stem cell (iPSC) SZGJMSi004-A line from a 28-year-old Han male patient with depression DOI Creative Commons

Xuyuan Yin,

Yuan Cai,

Ningning Jia

et al.

Stem Cell Research, Journal Year: 2024, Volume and Issue: 77, P. 103428 - 103428

Published: April 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.

Language: Английский

Citations

2
Patient-derived induced pluripotent stem cells: Tools to advance the understanding and drug discovery in Major Depressive Disorder DOI Creative Commons
Andreia Vaz, António J. Salgado, Patrícia Patrício

et al.

Psychiatry Research, Journal Year: 2024, Volume and Issue: 339, P. 116033 - 116033

Published: July 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

Language: Английский

Citations

2