Cell and Bioscience
·
2023
·Vol. 13
·期 1
·1-20
·
IF 7.5
Mi Kai,Li Yiqing,Yang Yuhang,Secombe Julie,Liu Xingyin
Background Drosophila melanogaster is excellent animal model for understanding the molecular basis of human neurological and motor disorders. The experimental conditions and chamber design varied between studies. Moreover, most previously established paradigms focus on fly trace detection algorithm development. A comprehensive understanding on how fly behaves in the chamber is still lacking. Results In this report, we established 74 unique behavior metrics quantifying spatiotemporal characteristics of adult fly locomotion and social behaviors, of which 49 were newly proposed. By the aiding of the developed analysis pipeline, Drosophila video tracking (DVT), we identified siginificantly different patterns of fly behavior confronted with different chamber height, fly density, illumination and experimental time. Meanwhile, three fly strains which are widely used as control lines, Canton-S(CS), w 1118 and Oregon-R (OR), were found to exhibit distinct motion explosiveness and exercise endurance. Conclusions We believe the proposed behavior metrics set and pipeline should help identify subtle spatial and temporal differences of drosophila behavior confronted with different environmental factors or gene variants.
研究领域:
神经生物学
·
行为学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BEHAVIOURAL NEUROLOGY
·
2023
·
IF 2.8
Lijuan Chen,Jing Li,Xinglian Liu,Zhiwei Zhao,Yan Jin,Yikun Fu,Aiqin Zhou,Chengqun Wang,Yan Zhou
Vitamin B6 (VB6) exhibits therapeutic effects towards autism spectrum disorder (ASD), but its specific mechanism is poorly understood. Rat dams were treated with VB6 standard, VB6 deficiency, or VB6 supplementary diet, and the same treatment was provided to their offspring, with their body weights monitored. Three-chambered social test and open field test were employed to evaluate the effect of VB6 on autism-like behaviors. Gamma-aminobutyric acid (GABA) generation and synaptic inhibition of neurons in the hippocampus of rat were detected via immunofluorescence staining, followed by the measurement of GABA concentration through high-performance liquid chromatography (HPLC). The role of VB6 in the autophagy and apoptosis of cells was determined via Western blot and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). In order to conduct rescue experiments, the inhibition of mammalian target of rapamycin (mTOR) or the activation of GABA was achieved by drug administration to the offspring rats with VB6 deficiency. As a result, no evident difference in weight was observed in the offspring with varied VB6 treatments. VB6 deficiency impaired social interaction; aggravated self-grooming and bowel frequency; decreased GABA concentration, VIAAT, GAD67, vGAT expressions, and LC3 II/LC3 I ratio; increased p62 level and p-mTOR/mTOR ratio; and promoted cell apoptosis. Inhibition of mTOR reversed the effect of VB6 deficiency on cell autophagy. GABA activation or mTOR inhibition offset the role of VB6 deficiency in autism-like behaviors and hippocampal GABA expression. Collectively, VB6 deficiency induces autism-like behaviors in rats by regulating mTOR-mediated autophagy in the hippocampus.
研究领域:
神经科学
·
药理学
·
行为科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCHIZOPHRENIA BULLETIN
·
2025
·
IF 4.8
Fan Rui,Pu Jianlin,Zhang Jin,Yu Minglan,Wang Tingting,Geng Xiaoqi,Dong Wei,Ma Rong,Wang Binglong,Wu Jianfei,Liu Kezhi,Hashimoto Kenji,Xiang Bo
BackgroundSocial withdrawal is a core symptom of schizophrenia (SCZ), yet its underlying molecular mechanisms remain unclear. Gα13 (GNA13), a G protein alpha subunit, has been implicated in SCZ susceptibility. This study investigated the role of Gα13 in social behavior by overexpressing it in the medial prefrontal cortex (mPFC) pyramidal neurons of mice.Study DesignIn this study, we first constructed CRE recombinase overexpressing Gα13 gene mice using CRISPR/Cas9 technology, tested the social behaviors by three-box socialization test, detected the changes of neuronal activities during social activities in mice by calcium signal fiber-optic recordings, observed the changes of dendritic spines by Golgi staining, applied RNA sequencing (RNA-Seq) to find the relevant targets, and observed whether it could reverse the abnormalities by pharmacological experiments social behavior. The electrophysiological characteristics of Gα13 overexpression were investigated using the whole-cell membrane clamp technique, followed by assessment of the severity of SCZ patients and social withdrawal using the PANSS scale and measurement of human plasma Gα13 protein levels using the ELISA technique, and the clinical correlation between the two was assessed.Study ResultsGα13 overexpression (Gα13-OE) mice exhibited significant social deficits in the three-chamber test, showing reduced sociability but normal social novelty recognition. Fiber photometry recordings revealed decreased neuronal activity during social interactions, and Golgi staining showed reduced dendritic spine density in mPFC pyramidal neurons. RNA-Seq identified downregulation of Adcyap1, affecting the cAMP/PKA signaling pathway and NMDA receptor (NMDAR) function. Pharmacological activation of Adcyap1 with PACAP-38 or NMDAR with D-cycloserine rescued the social deficits and restored synaptic function. Conversely, knockdown of Gα13 in an MK-801-induced SCZ mouse model ameliorated social behavior abnormalities. Clinically, patients with SCZ exhibited elevated plasma levels of Gα13, which positively correlated with the severity of social withdrawal symptoms measured by the PANSS G16 item.ConclusionsThese findings suggest that overexpression of Gα13 in the mPFC impairs social behavior by disrupting neuronal function and synaptic plasticity via the Adcyap1/cAMP/PKA/NMDAR pathway. Targeting Gα13 may offer a novel therapeutic strategy for addressing social deficits in SCZ.
研究领域:
神经生物学
·
精神病学
·
分子神经科学
·
信号转导
·
行为神经科学
·
转化医学
·
突触生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）