Jie Chen , Yujia Li , Xiaofei Huo , Ziqiang Huang , Suyun Li , Wenyu Cao , Cuilan Zhou , Yang Xu
{"title":"Targeted suppression of BRD7 with BI-9564 prevents seizure behaviors in pentylenetetrazol and pilocarpine-induced mouse model of epilepsy","authors":"Jie Chen , Yujia Li , Xiaofei Huo , Ziqiang Huang , Suyun Li , Wenyu Cao , Cuilan Zhou , Yang Xu","doi":"10.1016/j.bbr.2025.115549","DOIUrl":"10.1016/j.bbr.2025.115549","url":null,"abstract":"<div><div>Epilepsy is a serious neurological disorder, but its underlying cellular and molecular mechanisms remains incomplete. As a member of the bromodomain-containing protein (BCP) family, BRD7 has been implicated in a variety of cellular processes, including chromatin remodeling, transcriptional regulation, and cell cycle progression. However, the role of BRD7 in epilepsy in vivo is still poorly understood. In the present study, we found that pentylenetetrazole (PTZ)-induced epilepsy increased hippocampal BRD7, which was mainly localized in neurons. In addition, the enhanced expression of hippocampal BRD7 was normalized by using the anti-epilepsy drug valproic acid (VPA). Furthermore, we identified that the BRD7 inhibitor BI-9564 could dose dependently alleviated the seizure behavior in PTZ treated mice, which was also validated in pilocarpine mouse model. Mechanistically, the anti-seizure effect of BI- 9564 might be due to its negative-regulation of hippocampal TRPV4 that downregulated neuronal over-excitability. Importantly, BRD7 blockade retained its antiepileptic activity over chronic dosing that was not related to psychomotor or cognitive effects. To our knowledge, these results are the first evidence to demonstrate that BRD7 inhibitor can down-regulate neuronal over-excitation caused by epilepsy possible by regulating TRPV4. Targeting BRD7 through the development of selective inhibitors may lead to disease-modifying therapies that reduce seizure behavior.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"485 ","pages":"Article 115549"},"PeriodicalIF":2.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143687311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ravi Rana , Ritam Mukherjee , Sidharth Mehan , Zuber khan , Ghanshyam Das Gupta , Acharan S Narula
{"title":"Molecular Mechanisms of Neuroprotection: The Interplay of Klotho, SIRT-1, Nrf2, and HO-1 in Neurological Health","authors":"Ravi Rana , Ritam Mukherjee , Sidharth Mehan , Zuber khan , Ghanshyam Das Gupta , Acharan S Narula","doi":"10.1016/j.bbr.2025.115545","DOIUrl":"10.1016/j.bbr.2025.115545","url":null,"abstract":"<div><div>Neurological disorders significantly impair neuronal function and lead to cognitive and motor deficits. This review manuscript explores the therapeutic potential of key proteins—Klotho, SIRT-1, Nrf2, and HO-1—in combating these disorders. Neurological conditions encompass neurotraumatic, neurodegenerative, and neuropsychiatric diseases, all characterized by neuronal loss and dysfunction. The complex functions of Klotho, an anti-aging protein, and SIRT-1, a histone deacetylase, highlight their roles in neuronal survival and neuroprotection through the enhancement of antioxidant defences and the modulation of stress responses. Nrf2 functions as the principal regulator of the antioxidant response, whereas HO-1 facilitates the control of oxidative stress and the resolution of inflammation. Evidence suggests that the interplay between these proteins facilitates neuroprotection by decreasing oxidative damage and promoting cognitive function. The study emphasises the significance of signalling pathways, particularly the Nrf2/HO-1 axis, which are essential in mitigating oxidative stress and inflammation linked to neurodegenerative disorders. Future therapeutic strategies must consider personalized approaches, innovative drug delivery systems, and early intervention to optimize outcomes. This review provides a comprehensive framework for understanding how targeting these pathways can mitigate the burden of neurological disorders, advancing the development of effective interventions for enhancing brain health.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"485 ","pages":"Article 115545"},"PeriodicalIF":2.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143687317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaowei Xie , Linlin Fan , Ximei Chen , Yijun Luo , Hong Chen
{"title":"The resting-state brain activity and connectivity mediates the effect of overt narcissism on negative physical self","authors":"Xiaowei Xie , Linlin Fan , Ximei Chen , Yijun Luo , Hong Chen","doi":"10.1016/j.bbr.2025.115546","DOIUrl":"10.1016/j.bbr.2025.115546","url":null,"abstract":"<div><div>Overt narcissism is a stable personality trait in which individuals maintain a relatively positive self-image through self-improvement. Previous studies have suggested that examining the neurobiological processes behind personality could help to understand the mechanism by which the personality acts as a risk or protective factor. However, there is a lack of research investigating the neural mechanisms underlying the influence of overt narcissism on negative physical self (NPS). This study evaluated the resting state brain activity (fractional amplitude of low-frequency fluctuations, fALFF) and connectivity (functional connectivity, FC) of 1647 college students. Whole brain correlation analysis showed that overt narcissism was positively correlated with fALFF in the left insula, left precentral gyrus (PreCG) and bilateral superior temporal gyrus (STG). Moreover, overt narcissism exhibited a significant positive correlation with the right STG-PreCG connectivity, and also was significantly positively correlated with FC between the left STG and posterior cingulate gyrus, the left orbitofrontal cortex, the right inferior frontal gyrus and the right thalamus. The results of mediating analysis showed that fALFF in the left PreCG and the right STG-PreCG connectivity partially mediated the effects of overt narcissism on general and facial appearance of NPS, respectively. This study constructed a model (i.e., overt narcissism→brain regions/FC→NPS), providing neurobiological evidence for the relationship between overt narcissism and NPS.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"485 ","pages":"Article 115546"},"PeriodicalIF":2.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143687312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Letícia Yoshitome Queiroz , Luana Nunes Mariot , Ericks Sousa Soares , Carolina Urach Stahler , Gustavo Griebner , Gustavo de Moraes Machado , João M. Gissoni , Jaquelini Betta Canever , Regina Sordi , Helena Cimarosti
{"title":"Cecal slurry-induced sepsis in mice impairs cognition and decreases SUMO-2/3 conjugation","authors":"Letícia Yoshitome Queiroz , Luana Nunes Mariot , Ericks Sousa Soares , Carolina Urach Stahler , Gustavo Griebner , Gustavo de Moraes Machado , João M. Gissoni , Jaquelini Betta Canever , Regina Sordi , Helena Cimarosti","doi":"10.1016/j.bbr.2025.115544","DOIUrl":"10.1016/j.bbr.2025.115544","url":null,"abstract":"<div><div>Sepsis is characterized by multiple organ dysfunction, dysregulation of the response to the infection process, and a high mortality rate in intensive care units. In addition, individuals who overcome sepsis often manifest cognitive deficits associated with neuroinflammation resulting from the entry of pro-inflammatory cytokines into the brain. Post-translational protein modifications, such as SUMOylation, can regulate the expression of pro-inflammatory genes during sepsis. Since SUMO-2/3 can play a role in pathological conditions, our aim was to investigate a potential link between sepsis-induced cognitive decline and SUMOylation by this isoform. Firstly, the cecal slurry model was induced by intraperitoneally injecting male Swiss mice with different volumes of a cecal solution. Following assessment of body temperature, mass and septic scores, the groups that received 300 μL and 350 μL of the cecal solution were selected for the behavioural tests, as they presented signs of sepsis without excessive mortality. Surviving animals were evaluated for cognition/memory and anxious/depressive-like behaviours through the open-field, object recognition, Y-maze, and tail suspension tests. Subsequently, SUMO-2/3 conjugation was determined in samples from the hippocampus and prefrontal cortex by Western blotting. Mice in the septic groups showed decreased locomotor activity, anxious-and depressive-like behaviours, as well as impaired memory. These deficits were accompanied by a decrease in SUMO-2/3 conjugation in the hippocampus and prefrontal cortex at 24 h and 10 days after the induction of the cecal slurry model. Taken together, our findings suggest that SUMOylation is impaired in septic animals and this could be related to the behavioural deficits seen in the surviving mice.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"485 ","pages":"Article 115544"},"PeriodicalIF":2.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CB1 and CB2 receptors differentially modulate the cognitive impact of maternal immune activation and perinatal cannabinoid exposure","authors":"Han-Ting Chen , Ken Mackie","doi":"10.1016/j.bbr.2025.115543","DOIUrl":"10.1016/j.bbr.2025.115543","url":null,"abstract":"<div><div>Maternal immune activation (MIA) commonly arises in response to an infection during pregnancy. MIA elevates cytokine levels, triggering an inflammatory cascade, which may be detrimental to the developing nervous system. Similarly, cannabis use and exposure of the fetus to cannabinoids during pregnancy (PCE) may elicit neuroinflammation and lead to detrimental behavioral outcomes. This is particularly concerning as there has been a notable rise in cannabis use during pregnancy. This study endeavors to examine the interaction between MIA and PCE and elucidate the role of CB1 and CB2 receptors in MIA and PCE outcomes. To this end, we compared the impact of MIA, PCE and MIA+PCE in wildtype, CB1, and CB2 cannabinoid receptor knockout mice of both sexes. PCE was modeled by daily 3 mg/kg THC administration from gestational day 5 (GD5) to postnatal day 10. MIA was modeled by intravenous Poly (I:C) injection at GD16.5. Subsequently, we assessed emotional and cognitive behaviors of adult offspring. Adult male offspring of dams exposed to PCE or MIA were impaired in novel object recognition and the delayed alternation working memory tasks. Interestingly, these behavioral impairments were absent when MIA and PCE were combined. Cannabinoid receptor knockout studies found that CB1 receptors mediated behavioral deficits after PCE. In contrast CB2 receptors were necessary for full expression of MIA-induced behavioral impairments. Although females showed more modest behavioral changes after MIA or PCE, CB1 receptors were required for the PCE deficit and CB2 receptors were required for the MIA deficit also in females. Notably, lack of CB2 receptors in males prevented the “protection” following combined MIA + PCE, while CB1 knockout mice remained protected. Taken together, these results suggest a complex interplay between PCE, MIA and CB1 and CB2 cannabinoid receptors.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"485 ","pages":"Article 115543"},"PeriodicalIF":2.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Niels Hansen , Kristin Rentzsch , Anne Elisa Sagebiel , Sina Hirschel , Björn Hendrik Schott , Dirk Fitzner , Jens Wiltfang , Claudia Bartels
{"title":"Subjective cognitive decline in conjunction with cerebrospinal fluid anti-ATP1A3 autoantibodies and a low amyloid β 1–42/1–40 ratio: Report and literature review","authors":"Niels Hansen , Kristin Rentzsch , Anne Elisa Sagebiel , Sina Hirschel , Björn Hendrik Schott , Dirk Fitzner , Jens Wiltfang , Claudia Bartels","doi":"10.1016/j.bbr.2025.115541","DOIUrl":"10.1016/j.bbr.2025.115541","url":null,"abstract":"<div><h3>Background</h3><div>Animal studies reveal the role of the sodium/potassium transporting ATPase α-3 subunit (ATP1A3) in maintaining the resting membrane potential and thus in synaptic information processing and potentially cognitive disorders. However, autoantibodies against AT1A3 have not previously been reported in patients with subjective cognitive decline.</div></div><div><h3>Case presentation</h3><div>We report the case of a 57-year-old female who underwent neuropsychological testing, magnetic resonance imaging (MRI) and 18 F fluorodesoxyglucose positron emission tomography (FDG-PET) imaging, and cerebrospinal fluid (CSF) analysis. Neural autoantibodies were assessed in serum and CSF. We found a normal cognitive profile together with a self-reported cognitive decline, and such consistent with subjective cognitive decline (SCD). Analysis of the cerebrospinal fluid revealed anti-ATP1A3 autoantibodies. ATP1A3 autoantibodies were also detected in serum. Analysis of amyloid pathology markers in the CSF showed a slightly reduced amyloid β1–42/ amyloid β1–40 ratio. In view of the possible paraneoplastic autoantibodies, whole-body FDG-PET was performed, which did not reveal a malignancy-specific lesion. FDG-PET of the brain also showed no hypometabolism. We diagnosed SCD based on CSF-affirmed possible Alzheimer´s pathologic change with ATP1A3 autoantibodies in CSF and serum.</div></div><div><h3>Conclusions</h3><div>To our knowledge, this is the first report of CSF and serum ATP1A3 autoantibodies associated with SCD although an incidental finding cannot be fully excluded. In addition, amyloid pathology was detected via CSF biomarkers, suggesting that ATP1A3 autoantibodies are a potentially promising biomarker in SCD with an Alzheimer´s pathologic change if confirmed in large-scale studies.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"485 ","pages":"Article 115541"},"PeriodicalIF":2.6,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuemei Li , Xin Wang , Lifen Xue, Lan Luo, Lingxiao Hu, Wengao Jiang
{"title":"RAGE/AP-1/OTR signaling pathway in rat hippocampus DG involved in CUS induced depressive-like behaviors","authors":"Xuemei Li , Xin Wang , Lifen Xue, Lan Luo, Lingxiao Hu, Wengao Jiang","doi":"10.1016/j.bbr.2025.115540","DOIUrl":"10.1016/j.bbr.2025.115540","url":null,"abstract":"<div><div>There has been a growing body of evidence indicating that the oxytocin (OT) system plays a significant role in the neurophysiology of chronic stress-related mood disorders in recent years. However, the precise alterations for the OT system in response to chronic stress and the underlying mechanism remains unclear. The present study demonstrated that chronic unpredictable stress (CUS) resulted in a reduction in the expression of RAGE and OTR, as well as an inhibition of AP-1 phosphorylation. RAGE knockdown in hippocampus DG induced depressive-like behaviors, down-regulated the OTR protein and mRNA levels, and reduced the AP-1 phosphorylation. The administration of OT via the nasal route reversed the depressive-like behaviors induced by RAGE knockdown, increased the levels of BDNF expression and AP-1 phosphorylation. On the other hand, RAGE over-expression in the hippocampus DG resisted the effects of CUS on depression-like behaviors, AP-1 phosphorylation, and OTR expression. These finding suggested that RAGE signaling pathway is involved in CUS induced depressive-like behaviors at least partially by regulating OTR expression.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"485 ","pages":"Article 115540"},"PeriodicalIF":2.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhiding Wang , Wenhao Xu , Cheng Zhang , Chaoyue Zhang , Yinji Liu , Pinhong Chen , Gencheng Han , Lubin Wang
{"title":"Music boosts the recovery of attention after mental fatigue in healthy young male subjects: A human auditory event-related potential study","authors":"Zhiding Wang , Wenhao Xu , Cheng Zhang , Chaoyue Zhang , Yinji Liu , Pinhong Chen , Gencheng Han , Lubin Wang","doi":"10.1016/j.bbr.2025.115539","DOIUrl":"10.1016/j.bbr.2025.115539","url":null,"abstract":"<div><div>Daily life faces continuous cognitive tasks. Several methods could lessen cognitive fatigue including music. To find out how music functions in recovering cognitive fatigue, twenty-seven participants were randomly assigned to the rest group (N = 12) and the music group (N = 15). To evaluate the effects of Mozart K488 music on attention function after a continuous cognitively demanding task. Participants completed subjective questionnaires and the contingent negative variation (CNV) task before fatigue, after fatigue, and after the rest/musical intervention. EEG and ECG data were also collected during the experiment. The results showed that 5 min of Mozart K488 music resulted in improved CNV task performance in the musical intervention group. For EEG data, recoveries of the initial CNV and terminal CNV amplitude in Cz and CPz electrodes were observed and compared with the values after Mental Fatigue, which music increased the iCNV and tCNV. Alpha-ERD was lower after listening to music than after resting. Moreover, during music playing, compared to other brain regions the EEG alpha power of participants was significantly high in the central frontal region. This study demonstrates a short-term musical intervention can effectively boost the recovery of attention after Mental Fatigue.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"485 ","pages":"Article 115539"},"PeriodicalIF":2.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammad Hosein Naeimi Ghahroodi , Zahra Bahari , Mahdi Mashhadi Akbar Boojar
{"title":"Comparative analysis of analgesic and anxiolytic effects of alcoholic extracts from Eryngium billardieri and Urtica dioica in a rat model of chronic pain","authors":"Mohammad Hosein Naeimi Ghahroodi , Zahra Bahari , Mahdi Mashhadi Akbar Boojar","doi":"10.1016/j.bbr.2025.115537","DOIUrl":"10.1016/j.bbr.2025.115537","url":null,"abstract":"<div><h3>Objective</h3><div>The treatment of neuropathic pain is crucial, as it not only alleviates physical discomfort but also reduces anxiety associated with pain, ultimately enhancing the quality of life for affected individuals. This study investigates the protective effects of hydro-alcoholic extracts from <em>Eryngium billardieri</em> (Er) and <em>Urtica dioica</em> (Ur) on neuropathic pain and anxiety responses in an animal model.</div></div><div><h3>Methods</h3><div>40 male Wistar rats were used to investigate neuropathy induced by the chronic constriction injury (CCI) model. Animals were divided into five experimental groups (N = 8): [sham], [CCI], [CCI+Er], [CCI+Ur], and [CCI+Imipramine]. Er and Ur were administered orally for 30 days, starting on the day of surgery. Behavioral tests, including acetone for cold allodynia, the elevated plus maze for anxiety-like behaviors, and the open field for innate anxiety, were conducted on day −1 (before CCI) and on days 2, 4, 6, 14, 21, and 30. Data were analyzed by one-way analysis of variance test, and P < 0.05 was considered significant.</div></div><div><h3>Results</h3><div>Neuropathic surgery resulted in cold allodynia and anxiety-like behaviors throughout the experiment as compared to the sham. Er extract significantly decreased both cold allodynia and anxiety-like behaviors in the CCI group. However, Ur extract only significantly reduced cold allodynia (and not anxiety-like behaviors). Additionally, there was no difference between the analgesic effects of Er and Ur extracts.</div></div><div><h3>Conclusions</h3><div>These findings support the use of Er as a potential comprehensive treatment for neuropathic pain and anxiety symptoms. Future research should focus on exploring the specific mechanisms behind these effects and the potential for synergistic treatments to improve outcomes for individuals suffering from neuropathy.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"485 ","pages":"Article 115537"},"PeriodicalIF":2.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neuroprotective effect of nano-carboxymethyl chitosan from Doryteuthis sibogae against rotenone-induced Parkinson’s disease in the zebrafish model","authors":"Srinivasan Palaniselvam , Vignesh Narasimman , R. Vijayashree , Saravanan Ramachandran","doi":"10.1016/j.bbr.2025.115523","DOIUrl":"10.1016/j.bbr.2025.115523","url":null,"abstract":"<div><div>This study investigates the neuroprotective effects of N-carboxymethyl chitosan (N-CMC) against rotenone (ROT)-induced Parkinson's disease (PD) in a zebrafish (ZF) model. In vivo experiments revealed that ROT-exposed ZF larvae exhibited reduced locomotor activity, increased edge preference, and impaired touch response, while N-CMC treatment significantly improved these behavioral parameters. The reactive oxygen species (ROS) levels in ROT-exposed larvae were elevated (37.75 %) but decreased with N-CMC treatment (30.28 %). Apoptosis was also reduced from 38.87 % in ROT-exposed larvae to 16.52 % with N-CMC treatment. In vitro studies using the N2A cell line confirmed N-CMC’s neuroprotective effects. In adult ZF, ROT exposure decreased locomotion, and N-CMC treatment reversed these effects, as demonstrated through ToxTrac analysis. Novel Tank and Light/Dark tests showed significant behavioral improvements with N-CMC. Neurotransmitter analysis indicated increased dopamine, GABA, and glutamate levels in ROT-exposed ZF, which were moderated with N-CMC treatment. Gene expression analysis of gap43, syn2a, and tuba1b showed upregulation in ROT-exposed ZF, while N-CMC treatment downregulated these genes. Antioxidant assays demonstrated that ROT decreased SOD, CAT, and GSH levels in the brain, while N-CMC treatment increased these antioxidant levels by 1.3-fold, 7.5-fold, and 1.3-fold, respectively. Histopathology revealed neuronal degeneration in ROT-exposed ZF brains, but N-CMC treatment protected the neuronal loss. This study is the first to explore the neuroprotective and antioxidant properties of N-CMC in a ZF model, indicating its potential therapeutic benefits over conventional ROT-based treatments for PD.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"485 ","pages":"Article 115523"},"PeriodicalIF":2.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}