Journal of Neuroscience Research最新文献

{"title":"Modulation of Magnetic Resonance Spectroscopy Levels of Glutamate and GABA by Ketamine in Treatment-Resistant Depression","authors":"Stephanie Njau,&nbsp;Artemis Zavaliangos-Petropulu,&nbsp;Shantanu Joshi,&nbsp;John Brooks,&nbsp;Joseph O'Neill,&nbsp;Woods P. Roger,&nbsp;Viviane Norris,&nbsp;Randall T. Espinoza,&nbsp;Katherine L. Narr","doi":"10.1002/jnr.70102","DOIUrl":"10.1002/jnr.70102","url":null,"abstract":"<div>\u0000 \u0000 <p>Ketamine has emerged as a highly effective intervention for treatment-resistant depression (TRD). Though it acts as a non-competitive antagonist of excitatory N-methyl-D-aspartate receptors (NMDAR), widely expressed in the brain, including on inhibitory γ-aminobutyric acid (GABA)-ergic cells, the mechanisms of its antidepressant action are less clear. To investigate the links between glutamate and GABA neurotransmission and the clinical benefits of ketamine, we used proton magnetic resonance spectroscopy (¹H-MRS) to measure both glutamate and GABA levels in the dorsal anterior cingulate cortex (dACC) in 60 participants with TRD before (~within 1 week), and 24 h after a 40-min intravenous infusion with 0.5 mg/kg of racemic (<i>R,S</i>)-ketamine. The 17-item Hamilton Depression Rating Scale (HDRS₁₇) was used as the primary measure of clinical improvement, and a 50% or greater improvement in HDRS₁₇ ratings was used to define treatment responders. Ketamine increased mean dACC glutamate levels in responders only 24 h after treatment (<i>n</i> = 25, <i>p</i> = 0.01). Further, lower glutamate levels at baseline predicted greater improvements in HDRS₁₇ scores at 24 h post treatment (<i>p</i> &lt; 0.0001). However, GABA levels remained stable after treatment irrespective of response status (<i>p</i> = 0.90). Metabolites associated with neuronal integrity (tNAA), metabolic function (tCr), and membrane turnover (tCho), which may serve as complementary biological evidence of ketamine-induced plasticity, also increased with treatment (all <i>p</i> &lt; 0.01). Results provide evidence of sustained enhancements of neurotransmission or other glutamate-related metabolic effects following subanesthetic ketamine in responders and a potential role of ACC glutamate levels as a biomarker of responsivity to ketamine.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"104 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortical Hierarchy Collapse in Alzheimer's Disease: Connectome Gradient Compression as a Potential Biomarker","authors":"Mei-Ting Zhao,&nbsp;Qi Gong,&nbsp;Ran Chen,&nbsp;Yun Jiao,&nbsp;Alzheimer's Disease Neuroimaging Initiative","doi":"10.1002/jnr.70099","DOIUrl":"10.1002/jnr.70099","url":null,"abstract":"<div>\u0000 \u0000 <p>This investigation centered on Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by memory impairment and cognitive decline. Functional connectome gradient analysis was utilized to investigate alterations in the hierarchical architecture of brain networks in AD. The study cohort consisted of 222 subjects, encompassing 111 AD patients and 111 normal controls (NC). Connectome gradients were computed via a dimensionality reduction technique based on diffusion map embedding and analyzed at both the region of interest (ROI) and network levels. Additional connectome gradient metrics, including network median distance and gradient eccentricity, were calculated, and the relationship between connectome gradients and rich-club organization was assessed. These connectome gradient values were subsequently correlated with clinical cognitive scores. The results demonstrated a significant reduction in the principal gradient range in AD patients. At the network level, gradient values exhibited an increase in the somatomotor (SMN) and visual networks (VIS), while decreasing in the default mode (DMN) and frontoparietal networks (FPN) relative to controls. Analyzes of network mean distance and gradient eccentricity further revealed compression of the brain cortical hierarchy in AD patients. Furthermore, rich-club analyzes indicated a reduction in the gradient value difference between hub and peripheral nodes in AD patients. Finally, clinical correlation analysis revealed a positive correlation between the degree of cognitive impairment and the degree of compression of the brain cortical hierarchy. These findings provide a novel perspective on the study of brain network organization in AD patients, contributing to a more comprehensive understanding of the neural mechanisms underlying Alzheimer's disease.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repetitive Blast Exposure Drives Chronic Pain in Female Rats","authors":"Amirah Wright,&nbsp;Susan F. Murphy,&nbsp;Pamela J. VandeVord","doi":"10.1002/jnr.70103","DOIUrl":"10.1002/jnr.70103","url":null,"abstract":"<p>Clinical studies have established that repeated blast traumatic brain injury (rbTBI) can result in chronic pain conditions, with outcomes exhibiting notable sex-dependent differences. However, limited preclinical rbTBI models have systematically investigated the behavioral and neuropathological outcomes of female subjects. In the present study, adult female rats were subjected to repeated blast exposures, and the subsequent development of chronic pain–related behaviors and neuropathological changes was assessed. Repeated blast events induced robust mechanical and thermal hypersensitivity beginning 48 h post-injury and persisted through 12 weeks, accompanied by anxiety and depressive-like behaviors at the chronic time point. These behavioral alterations were associated with increased glial activity, as evidenced by Glial Fibrillary Acidic Protein (GFAP) and Ionized Calcium-Binding Adaptor Molecule 1 (IBA-1) in the frontal cortex and posterior nucleus regions at 12 weeks following injury. Notably, expression levels of neuropeptide markers, Calcitonin Gene-Related Peptide (CGRP) and Substance P (SP), remained unchanged. Collectively, these findings suggest that chronic pain behaviors following rbTBI in females are mediated primarily by sustained glial activation rather than neuropeptide dysregulation.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12714028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequency and Timing-Dependent Effects of Ultrasound on Neural Responses: Comparative Analysis With Whisker Stimulation in Rats","authors":"Ye Yuan,&nbsp;Tian Liu,&nbsp;Jue Wang","doi":"10.1002/jnr.70100","DOIUrl":"10.1002/jnr.70100","url":null,"abstract":"<div>\u0000 \u0000 <p>This study explores whether ultrasound can induce short-term synaptic plasticity (STP)-like effects at the systems level by modulating cortical excitability and sensory responsiveness. We designed a temporally shifted sensory paradigm to test how ultrasound frequency (1, 2, and 4 MHz), inter-stimulus interval (10, 25, and 100 ms), and stimulation order (ultrasound–whisker vs. whisker–ultrasound) affect cortical responses in the rat barrel cortex. Thirty Sprague–Dawley rats underwent an identical experimental protocol. Electrocorticography (ECoG) signals were recorded from the C2 barrel column, and neural responses were assessed by peak amplitude, latency, and power spectral density. Whisker stimulation alone evoked strong cortical responses, significantly greater than ultrasound stimulation. Notably, when ultrasound preceded whisker stimulation by 25 ms, subsequent whisker responses were significantly enhanced, suggesting the existence of a cortical “excitability window” for neuromodulation. This facilitation effect was absent with time intervals of 10 and 100 ms. Mechanistically, ultrasound may modulate membrane tension and activate mechanosensitive ion channels to transiently lower the activation threshold of cortical neurons. These findings reveal that ultrasound can temporally enhance cortical excitability and sensory responsiveness in a frequency- and timing-dependent manner. Our results provide systems-level evidence of STP-like neuromodulation and provide the potential of ultrasound as a noninvasive method for dynamic control of sensory processing.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabidiol as a Neuroprotective Agent in Acrylamide-Induced Neurotoxicity: Effects on Oxidative Stress, Inflammation, and Cholinergic Function in Male Mice","authors":"Korina Atsopardi,&nbsp;Konstantinos Mesiakaris,&nbsp;Ioannis Sotiropoulos,&nbsp;Marigoula Margarity,&nbsp;Konstantinos Poulas","doi":"10.1002/jnr.70098","DOIUrl":"10.1002/jnr.70098","url":null,"abstract":"<p>The neuroprotective potential of cannabidiol (CBD) was assessed in a mouse model of acrylamide-induced neurotoxicity. Acrylamide (AA), an environmental and dietary pollutant, is known to cross the blood–brain barrier and induce oxidative stress, inflammation and neurotoxic effects. Male C57BL/6 mice were randomly assigned to four groups: Control (Con), Acrylamide (AA), Cannabidiol (CBD), and a combination treatment (AA + CBD). The AA group received acrylamide (10 mg/kg, i.p.) daily for 5 days. CBD was administered (10 mg/kg, i.p.) for 10 days in the CBD and AA + CBD groups. In the AA + CBD group, acrylamide (10 mg/kg, i.p.) was co-administered during the last 5 days of CBD treatment. Behavioral outcomes were analyzed using the open field test, revealing that CBD mitigated anxiety-like behavior induced by acrylamide, enhancing movement and center exploration. Further, CBD treatment modulated oxidative stress responses, reducing MDA levels and partially restoring antioxidant markers (GSH, SOD, and CAT) in the hippocampus and striatum. Inflammatory markers were also assessed, revealing that acrylamide elevated pro-inflammatory cytokines TNF-α and IL-6. Notably, CBD co-treatment reduced TNF-α levels in the hippocampus and cortex and attenuated IL-6 levels in the cortex and striatum, suggesting an anti-inflammatory effect. Additionally, CBD modulated neuroplasticity by increasing BDNF levels in the hippocampus, counteracting the reduction caused by acrylamide. CBD also influenced cholinergic activity by restoring Ach levels and altering AChE activity across brain regions. Findings suggest that CBD exhibits neuroprotective properties by reducing oxidative stress, inflammation and cholinergic dysregulation, thereby offering a promising therapeutic approach for mitigating pollutant-induced neurotoxicity and potentially treating neurodegenerative disorders.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12704046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145756903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Repetitive Transcranial Magnetic Stimulation Combined With Cognitive Training of Response Inhibition on Task-Related Oscillatory Activity","authors":"Xiaomin Xu,&nbsp;Adriano H. Moffa,&nbsp;Mei Xu,&nbsp;Thanh Vinh Cao,&nbsp;Colleen K. Loo,&nbsp;Donel M. Martin,&nbsp;Stevan Nikolin","doi":"10.1002/jnr.70101","DOIUrl":"10.1002/jnr.70101","url":null,"abstract":"<div>\u0000 \u0000 <p>Repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training (CT) has been explored as a potential novel method to improve response inhibition, but its neural mechanisms remain unclear. This study investigated the effects of rTMS + CT on oscillatory activity across different frequency bands and theta-gamma phase-amplitude coupling during the Stroop task. Sixty healthy participants were randomly assigned to receive four sessions of either active or sham prolonged intermittent theta burst stimulation (iTBS) + CT. Each session involved iTBS over both the right inferior frontal cortex and the pre-supplementary motor area, with participants completing the Stop Signal training task first, followed by the Go/No-Go training task. The Stroop task was administered before and immediately after the intervention while electroencephalography was recorded. There was a significant group effect on the change in beta desynchronization during incongruent trials (<i>t</i> = −2.03, <i>p</i> = 0.048), with a significant decrease observed in the active group (<i>p</i> = 0.03) and no change in the sham group (<i>p</i> = 0.83). Additionally, changes in gamma synchronization differed between groups for congruent trials (<i>t</i> = 2.28, <i>p</i> = 0.03), though neither group showed a significant pre-post change (<i>p</i> &gt; 0.05). Our study suggests that four sessions of iTBS + CT may modulate beta and gamma oscillations during the Stroop task, potentially enhancing motor inhibition and processing speed in response inhibition. These results provide neurophysiological insights into the neural mechanisms through which rTMS + CT may enhance response inhibition.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145756970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-Processing Circuits Among Depressed Youth After Amygdala Neurofeedback Cued to the Self-Face","authors":"Sewon Oh,&nbsp;Niki Hosseini-Kamkar,&nbsp;Carmen Santana-Gonzalez,&nbsp;Janani Ranatunga,&nbsp;Giang-Hoang Nguyen,&nbsp;Matthew Maurice,&nbsp;Kymberly Young,&nbsp;Karina Quevedo","doi":"10.1002/jnr.70097","DOIUrl":"https://doi.org/10.1002/jnr.70097","url":null,"abstract":"<p>Major depressive disorder is a significant health concern among adolescents due to its link to suicide and lifetime impairments. Current treatments yield limited success, but real-time functional magnetic resonance imaging (RT-fMRI) neurofeedback (NF) is a promising intervention. We tested the effects of RT-fMRI neurofeedback on the modulation of neural circuitry underlying self-referential processing and emotion regulation in youth trying to up-regulate the amygdala-hippocampus (AMYHIPP) complex. We examined amygdala functional connectivity during a self-other face recognition task before and after RT-fMRI NF from the AMYHIPP complex. (1) Depressed youth showed higher bilateral amygdala to anterior cingulate cortex (ACC), superior temporal and frontal gyri connectivity compared to controls, who showed lower connectivity before NF. Yet after NF, this pattern reversed, with depressed youth showing lower bilateral amygdala connectivity than controls. (2) Depressed youth showed <i>increased right</i> amygdala-cuneus connectivity while controls showed <i>increased left</i> amygdala-cuneus connectivity during self-other face recognition. (3) Lower right amygdala-cuneus connectivity was linked to improved rumination. Higher left amygdala-cuneus connectivity was linked to improved depression. (4) Shifts of less right versus left amygdala to superior middle temporal gyri connectivity after neurofeedback, and of more right versus left amygdala to middle frontal gyrus after NF, were linked to higher AMYHIPP engagement during training. This is suggestive of NF training effects upon implicit versus explicit emotion circuits. Caution is necessary regarding the meaning of symptoms to circuits associations and putative mechanisms of neurofeedback training given the lack of a placebo group.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145739810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disrupted Transcriptional Networks in Mammalian Cells Stably Over-Expressing Pathogenic Atrophin-1","authors":"Oluwademilade Nuga,&nbsp;Masoumeh Pourhadi,&nbsp;Julia P. Rausch,&nbsp;Sokol V. Todi","doi":"10.1002/jnr.70089","DOIUrl":"10.1002/jnr.70089","url":null,"abstract":"<div>\u0000 \u0000 <p>Dentatorubral-Pallidoluysian Atrophy (DRPLA) is a dominant neurodegenerative disease caused by CAG triplet repeat expansion in <i>ATN1</i>, which encodes the transcriptional co-repressor Atrophin-1. DRPLA features motor, cognitive, and epileptic symptoms and shares pathogenic mechanisms with other polyglutamine (polyQ) disorders, including protein misfolding, impaired autophagy, and transcriptional dysregulation. To understand disease mechanisms, we performed RNA-seq on HEK293T cells stably over-expressing wild-type or pathogenic ATN1. Cells expressing pathogenic ATN1 exhibited a distinct transcriptomic profile, including disruptions in synaptic organization, extracellular matrix remodeling, ion channel expression, and neurotransmission. Several genes tied to neurodevelopmental, neurodegenerative, and oncogenic pathways were fully activated or silenced. Dysregulated pathways also included inflammation, chromatin remodeling, stress responses, and redox imbalance. Heat shock protein expression changes suggested proteotoxic stress and impaired protein quality control, with some findings conserved in a previously reported <i>Drosophila melanogaster</i> model of DRPLA. The transcriptomic signatures that we describe here expand understanding of the normal functions of ATN1 and the biology of disease of DRPLA.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Male-Specific Ventromedial Hypothalamic Nucleus Glutamate Decarboxylase (GAD)-2/GAD65 Regulation of Counterregulatory Transmitter Marker Gene Expression and Peripheral Hormone Profiles","authors":"Madhu Babu Pasula,&nbsp;Subash Sapkota,&nbsp;Rajesh Yadav,&nbsp;Karen P. Briski","doi":"10.1002/jnr.70094","DOIUrl":"10.1002/jnr.70094","url":null,"abstract":"<div>\u0000 \u0000 <p>The amino acid neurotransmitter gamma-aminobutyric acid (GABA) reportedly acts by unidentified ventromedial hypothalamic mechanisms to suppress hypoglycemia-associated counterregulatory endocrine function in male rats. Present studies addressed the premise that GABAergic transmission of ventromedial hypothalamic nucleus (VMN) origin may regulate dorsomedial VMN (VMNdm) growth hormone-releasing hormone (Ghrh)/steroidogenic factor-1 (SF-1) neuron counterregulatory signaling to control this hormone outflow. VMN glutamate decarboxylase-2 (GAD2/GAD₆₅) gene knockdown increased basal but inhibited insulin-induced hypoglycemia (IIH)-associated augmentation of corticosterone and glucagon secretion, while suppressing growth hormone secretion regardless of glucose status. Multiplex qPCR analysis of laser-catapult-microdissected VMNdm Ghrh-immunoreactive neurons showed that GAD2 siRNA pretreatment intensified IIH-associated upregulation of mRNAs that encode the counterregulatory-enhancing neurochemicals nitric oxide and glutamate, and exacerbated hypoglycemic downregulation of GAD1, GAD2, and SF-1 transcription. VMN GAD2 gene silencing augmented hypoglycemic enhancement of Ghrh neuron 5′-AMP-activated protein kinase alpha-1 and alpha-2 gene expression. VMN GAD2 gene knockdown exacerbated both positive lactate receptor and negative estrogen receptor transcriptional reactivity to IIH. Study outcomes provide novel evidence for bidirectional, glucose status-specific VMN GABAergic control of corticosterone and glucagon secretion in male rats, which is not documented in the other sex. Data verify GABA regulation of VMN dorsomedial Ghrh neuron metabolic and hormonal signal reception, energy screening, and counterregulatory neurochemical release. Further effort is needed to characterize the impact of GABA-dependent neurotransmission by this discrete VMN neuron population on neural circuitries that govern glucose homeostasis.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Propofol Alleviates Depression-Like Behavior and Cognitive Disorder in Learned Helplessness Model Mice via Regulating Synaptic Function","authors":"Jiarong Wang,&nbsp;Jinchen Xiang,&nbsp;Xuemei Han,&nbsp;Jing Liang,&nbsp;Xueliang Shang","doi":"10.1002/jnr.70096","DOIUrl":"10.1002/jnr.70096","url":null,"abstract":"<div>\u0000 \u0000 <p>Propofol, an anesthetic known for its safety, efficacy and neuroprotective properties, has potential novel antidepressant effects. However, its specific mechanisms still require further elucidation. Presently, we established a learned helplessness (LH) depression model to investigate the effects of propofol treatment on depression-like impairment. Thirty adult male C57BL/6j mice were randomly divided into three groups: control group (CON), model group (LH), and propofol group (PRO), with 10 mice per group. Behavioral analyses were conducted using weight measurement, sucrose preference test (SPT), forced swim test (FST), tail suspension test (TST), and Morris water maze test (MWM). Subsequently, HE staining was performed to examine pathological changes in the hippocampal region. Western blotting was conducted to assess changes in Notch signaling pathway components, synaptic plasticity-related proteins, and proteins in the glutamate system. Immunofluorescence was used to detect expression changes of NICD, SYP, and DCX. Hippocampal glutamate concentration was determined using a glutamate assay kit. Consequently, stressed mice exhibited pronounced depressive behaviors and decreased spatial learning and memory, accompanied by significant neuronal death in the dentate gyrus of the hippocampal region and reduced levels of neuronal regeneration as well as synaptic plasticity. Additionally, glutamate reuptake function was impaired in depression, manifested specifically as increased glutamate concentrations in the hippocampal region and neuronal glutamate transmission levels. Meaningfully, propofol upregulated Notch signaling pathway activity and improved glutamate reuptake function significantly resulting in enhanced adult hippocampal neurogenesis and synaptic plasticity. These findings demonstrated the effectiveness of propofol as a potential antidepressant and contributed to discovering novel antidepressant drugs.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}