Brain Research最新文献

{"title":"Levofloxacin-induced seizure susceptibility involves both enhanced glutamatergic and impaired GABAergic synaptic function","authors":"Kunmei He ,&nbsp;Lina He ,&nbsp;Xing Wei ,&nbsp;Xiaojuan Wang ,&nbsp;Muhua Zhou ,&nbsp;Yingying Cao ,&nbsp;Xibao Luo ,&nbsp;Junrui He","doi":"10.1016/j.brainres.2025.149929","DOIUrl":"10.1016/j.brainres.2025.149929","url":null,"abstract":"<div><div>Levofloxacin (LVFX)-associated seizures are thought to arise from disrupted excitatory-inhibitory balance, but the underlying synaptic mechanisms remain unclear. This study investigated how LVFX alters both glutamatergic and GABAergic transmission to promote neuronal hyperexcitability. We combined <em>in vitro</em> and in vivo approaches using primary cortical neurons treated with LVFX and adult rats administered LVFX. Electrophysiological recordings assessed AMPA receptor (AMPAR)-mediated miniature excitatory postsynaptic currents (mEPSCs) and GABAergic miniature inhibitory postsynaptic currents (mIPSCs). Molecular analyses examined vesicular glutamate transporter 1 (VGluT1) and vesicular GABA transporter (VGAT) expression, along with AMPAR subunit GluA1 trafficking dynamics. Seizure susceptibility was evaluated using magnesium-free conditions <em>in vitro</em> and pentylenetetrazol challenge in vivo. LVFX treatment significantly increased mEPSC frequency and amplitude while decreasing mIPSC frequency, indicating enhanced excitatory and suppressed inhibitory synaptic transmission. These changes were accompanied by upregulated VGluT1 and downregulated VGAT protein expression. The drug specifically altered GluA1 trafficking by decreasing internalization and promoting recycling to the plasma membrane. These synaptic modifications resulted in heightened seizure susceptibility, with LVFX-treated neurons showing earlier epileptiform discharges and pretreated animals exhibiting significantly reduced seizure latency. LVFX lowers seizure threshold by simultaneously enhancing glutamatergic transmission and suppressing GABAergic inhibition, providing a mechanistic basis for its pro-convulsant effects.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149929"},"PeriodicalIF":2.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIF-1α in glioblastoma multiforme cells: Mechanisms involving the Wnt/β-catenin signaling pathway","authors":"Jian Shen ,&nbsp;Yunnong Song ,&nbsp;Genghuan Wang,&nbsp;Jinjun Zhu,&nbsp;Gongjie Yu","doi":"10.1016/j.brainres.2025.149919","DOIUrl":"10.1016/j.brainres.2025.149919","url":null,"abstract":"<div><div>Glioblastoma multiforme (GBM) is a rapidly progressing brain malignancy, with its progression closely tied to a hypoxic microenvironment. Hypoxia-inducible factor-1α (HIF-1α) acts as a vital regulator in tumor adaptation to low oxygen levels, and its relationship with the Wnt/β-catenin signaling pathway exerts significant functions in the malignant properties of GBM. In this research, Western blot and qRT-PCR were applied to check β-catenin and HIF-1α expression in GBM. How HIF-1α influenced GBM cell behavior was investigated <em>in vitro</em> through the construction of U251 cell models with HIF-1α overexpression and knockdown, accompanied by assessments of cell proliferation, migration, invasion, and apoptosis. Additionally, co-immunoprecipitation (Co-IP) experiments were leveraged for checking the interaction of β-catenin and HIF-1α. This study demonstrated that HIF-1α and β-catenin were markedly upregulated in GBM tissues relative to normal controls, and their expression was positively correlated at the transcriptional level. In oxygen-limited environments, HIF-1α expression was significantly enhanced, and the Wnt signaling pathway was activated through stabilizing β-catenin. Functional experiments showed that HIF-1α overexpression facilitated cell proliferation, migration, and invasion, while inhibiting apoptosis; conversely, HIF-1α knockdown led to a significant reduction in these processes. Taken together, HIF-1α regulates the Wnt/β-catenin signaling pathway via its engagement with β-catenin, thereby promoting GBM proliferation and invasion, and inhibiting apoptosis. These findings emphasize the importance of HIF-1α in GBM advancement and suggest novel therapeutic strategies targeting HIF-1α and the Wnt/β-catenin pathway.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149919"},"PeriodicalIF":2.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting infant vocabulary from neural connectivity and maternal speech: A machine learning approach","authors":"Brigitta Tóth ,&nbsp;Gábor P. Háden ,&nbsp;Ildikó Tóth ,&nbsp;Krisztina Lakatos ,&nbsp;Anna Kohári ,&nbsp;Katalin Mády ,&nbsp;Bence Kas ,&nbsp;Dénes Tóth ,&nbsp;Ádám Szalontai ,&nbsp;Uwe D. Reichel ,&nbsp;István Winkler","doi":"10.1016/j.brainres.2025.149892","DOIUrl":"10.1016/j.brainres.2025.149892","url":null,"abstract":"<div><div>Identifying early predictors of language development is essential for understanding how infants acquire vocabulary during the first years of life. While previous studies have established the importance of infant-directed speech (IDS) and neural speech processing, this longitudinal study introduces a novel approach by combining EEG-based functional connectivity analysis and machine learning to assess the joint contribution of maternal and infant neural factors to language outcomes. Data were collected at birth and nine months, including maternal personality and speech characteristics, alongside infant EEG responses during speech processing. Language comprehension and production were assessed at 18 months using a standardized measure. A machine learning framework was used to model the predictive contribution of these variables, revealing that maternal speech prosody and EEG network properties were among the strongest predictors of later vocabulary. These findings highlight the value of integrating neural and environmental data using data-driven approaches and suggest targeted directions for future research on early language acquisition.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149892"},"PeriodicalIF":2.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DHYZ modulates hippocampal cholinergic pathway acetylation to ameliorate cognitive deficits post-ischemic stroke in rats","authors":"Zhihao Liu ,&nbsp;Xiaojian Shi ,&nbsp;Xiaoyan Xu ,&nbsp;Yingming Hu ,&nbsp;Yiwei Wen ,&nbsp;Xin Wang ,&nbsp;Lei Ye ,&nbsp;Jianwei Gong","doi":"10.1016/j.brainres.2025.149926","DOIUrl":"10.1016/j.brainres.2025.149926","url":null,"abstract":"<div><div>Ischemic stroke is a serious cerebrovascular disease that is often accompanied by debilitating sensorimotor deficits and persistent cognitive deficits, which seriously affect patients’ quality of life. DHYZ, a traditional Chinese herbal formula, has shown significant efficacy in restoring neurological function in ischemic regions of the brain, but its potential for improving poststroke cognitive impairment remains underdeveloped. In this study, the middle cerebral artery occlusion/reperfusion (MCAO/R) model was used to reproduce the pathological process of ischemic stroke in humans. We systematically investigated the therapeutic effect of DHYZ on poststroke cognitive dysfunction and the underlying mechanisms through a combination of behavioral assessment (Morris water maze), histopathological evaluation, molecular analysis (quantitative PCR, immunofluorescence, and Western blotting), and acetylcholine (ACh) content detection. The experimental data revealed that DHYZ treatment significantly reduced the volume of cerebral infarction, improved neurological recovery, and enhanced spatial learning/memory ability in MCAO/R rats. DHYZ enhanced the activation of hippocampal cholinergic circuits in MCAO/R rats, promoted the upregulation of CREB-binding protein (CBP) expression by increasing CREB phosphorylation and further increased the acetylation levels of the promoters of the acetylcholine transferase (ChAT) and acetylcholinesterase (AChE) genes in the hippocampus. This cascade enhances acetylation of the choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) gene promoters in the hippocampal pathway. The effects of ChAT and AChE on ACh balance each other and promote cognitive function. Our findings elucidate a novel mechanism involving the regulation of cholinergic signaling pathways and provide new insights for the development of effective interventions targeting ischemic stroke-related cognitive dysfunction.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149926"},"PeriodicalIF":2.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effects of Lactiplantibacillus plantarum and Pediococcus pentosaceus strains against oxidative stress via modulation of Nrf2-mediated antioxidation and anti-apoptosis","authors":"Yu-Rim Lee,&nbsp;Kyung-Min Park,&nbsp;Na-Kyoung Lee,&nbsp;Hyun-Dong Paik","doi":"10.1016/j.brainres.2025.149925","DOIUrl":"10.1016/j.brainres.2025.149925","url":null,"abstract":"<div><div>Oxidative stress leads to neurodegenerative diseases such as Parkinson’s, Alzheimer’s, and Huntington’s diseases. Therefore, we isolated <em>Lactiplantibacillus plantarum</em> and <em>Pediococcus pentosaceus</em> strains from kimchi and investigated the neuroprotective effects of the heat-killed lactic acid bacteria (LAB) strains against oxidative stress. All LAB strains demonstrated suitable probiotic characteristics. The heat-killed LAB strains exhibited strong antioxidant activities by effectively scavenging free radicals. To mimic gut–brain axis communication, conditioned medium (CM) was generated by incubating the heat-killed LAB strains with HT-29 intestinal cells. The LAB-CM was then applied to SH-SY5Y neuroblastoma cells to evaluate their neuroprotective effects against oxidative stress. The LAB-CM protected SH-SY5Y cells against hydrogen peroxide (H₂O₂)-induced oxidative stress, as evidenced by improved cell viability, reduced lactate dehydrogenase (LDH) release, morphological preservation, and suppression of reactive oxygen species (ROS) production. The heat-killed LAB strains enhanced brain-derived neurotrophic factor (<em>BDNF</em>) and tyrosine hydroxylase (<em>TH</em>) mRNA expression in HT-29 cells, contributing to increased <em>BDNF</em> and <em>TH</em> levels in the LAB-CM. Furthermore, the LAB-CM activated Kelch-like ECH-associated protein 1 (Keap1)/Nuclear factor erythroid 2-related factor 2 (Nrf2)/Heme oxygenase-1 (HO-1) signaling pathway, increasing the expression of antioxidant enzymes, including NAD(P)H quinone oxidoreductase 1 (NQO1), thioredoxin reductase 1 (TXNRD1), superoxide dismutase 1 (SOD1), and catalase (CAT). It also modulated Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) and inhibited the activation of cysteine-aspartic acid protease-9 (caspase-9) and caspase-3, thereby alleviating oxidative stress-induced neuronal apoptosis. Thus, <em>L. plantarum</em> WB3809 and <em>P. pentosaceus</em> WB3812 have the potential to be used as functional food ingredients with neuroprotective effects via antioxidant and anti-apoptotic mechanisms.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149925"},"PeriodicalIF":2.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing of METTL14 attenuates experimental intracerebral hemorrhage by suppressing TFRC-mediated ferroptosis","authors":"Limei Yu,&nbsp;Peng An","doi":"10.1016/j.brainres.2025.149927","DOIUrl":"10.1016/j.brainres.2025.149927","url":null,"abstract":"<div><div>Ferroptosis is emerging as a pathological mechanism of intracerebral hemorrhage (ICH), and inhibiting ferroptosis contributes to improving prognosis. N6-methyladenosine (m6A) methylation is a common RNA modification that is involved in disease progression. This study aimed to explore the effect of METTL14, a m6A transmethylase, on ferroptosis and the molecular mechanism, and identify its role in ICH progression. PC12 cells were stimulated with hemin to induce injury, and mice were injected with type IV collagenase to generate the ICH model. Ferroptosis was evaluated by detecting Fe2+, reactive oxygen species, and reduced glutathione levels. M6A methylation was assessed by methylated-RNA immunoprecipitation (Me-RIP), RIP, dual-luciferase reporter assay, and actinomycin D treatment. The results showed that hemin induced ferroptosis of PC12 cells. METTL14 was highly expressed in hemin-treated PC12 cells and ICH mice, and knockdown of METTL14 reversed the promotion of ferroptosis induced by hemin. Mechanically, METTL14 knockdown inhibited m6A modification of TFRC and reduced its stability at RNA level, which was recognized by IGF2BP2. Overexpression of TFRC reversed the inhibition of ferroptosis caused by METTL14 silence both in vitro and in vivo. In conclusion, silencing of METTL14 ameliorates ICH by inhibiting ferroptosis through suppressing m6A methylation of TFRC. These findings suggest that targeting m6A methylation and ferroptosis may be a promising strategy for ICH therapy.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149927"},"PeriodicalIF":2.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Being only with yourself enhances the binding of stimulus representations with both egocentric- and allocentric-representations of the self: A P2 event-related potential study","authors":"Sujata Sinha ,&nbsp;Ashley Chau-Morris ,&nbsp;J. Bruno Debruille","doi":"10.1016/j.brainres.2025.149898","DOIUrl":"10.1016/j.brainres.2025.149898","url":null,"abstract":"<div><div>Perceiving a stimulus involves the awareness that it is we who are perceiving it. Representations activated by the stimulus are thus automatically bound to representations of the self. Interestingly, previous research has shown that the amplitude of the P2 event-related brain potential (ERP) is larger for stimuli to which participants can refer themselves. This suggests that the P2 may index the binding of stimulus representations with self-representations and that this binding is modulable, like other automatic processes. P2 amplitudes could then be larger in participants who are only with themselves than in those with a friend (PwFs). Consistently, we found larger P2s in alones (n = 53) than in PwFs (n = 47) at two scalp locations. Firstly, at the midline central electrode, where large self-referencing effects were previously observed, indicating stronger binding with egocentric self-representations. Secondly, at the left temporo-occipital sites, suggesting stronger allocentric self-representation binding. Furthermore, these P2 effects were maximal for words with richer meanings, that is, for equivocal ones, intermediate for unequivocal-, and minimal for meaningless stimuli. P2 amplitude was thus modulated not only by current self-representations but also by stimulus representations, in accordance with the idea that it indexes their binding.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149898"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The neurobehavioral impact of stress and the therapeutic role of valproic acid in a PTSD animal model","authors":"Mohammad Saleh Hajghani ,&nbsp;Mansoureh Sabzalizadeh ,&nbsp;Ali Shamsara ,&nbsp;Taherh Haghpanah ,&nbsp;Mohammad Haghani ,&nbsp;Amir Abbas Arabpour ,&nbsp;Melika Farhadi ,&nbsp;Mohammad Reza Afarinesh","doi":"10.1016/j.brainres.2025.149922","DOIUrl":"10.1016/j.brainres.2025.149922","url":null,"abstract":"<div><div>This study examines the impact of stress on cognitive and behavioral functions and evaluates Valproic Acid (VPA) as a potential therapy in a mouse model of Post-Traumatic Stress Disorder (PTSD). Sixty-three male mice were assigned to control, PTSD, VPA, and PTSD + VPA groups, with behavioral assessments including anxiety, social interaction, memory, and depression-like tests. Histological analyses assessed neuronal integrity in the hippocampus, amygdala, cingulate cortex, and insula cortex. Stress significantly impaired cognitive performance, indicated by a lower Preference Index (PI%) in the novel object recognition task. Social interaction tests revealed decreased engagement in the PTSD group, reflecting social withdrawal. Behavioral assessments indicated increased immobility time in the tail suspension and forced swimming tests among PTSD mice, suggesting depression-like behaviors. In contrast, VPA treatment reduced immobility time, with the PTSD + VPA group showing improvements comparable to controls. Histological evaluations showed a higher percentage of degenerated cells in the hippocampus, amygdala, cingulate cortex, and insula cortex of the PTSD group versus controls. VPA administration significantly lowered the percentage of degenerated cells in the PTSD + VPA group, indicating neuroprotective effects, which were also noted in the hippocampus, amygdala, cingulate cortex, and insula cortex. These findings suggest VPA’s potential as a therapeutic agent for PTSD, warranting further pharmacological investigation.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149922"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remote ischemic conditioning as a potential therapy for Parkinson’s Disease: Inhibiting TLR4-Driven neuroinflammation and oxidative damage","authors":"Lipeng Cai ,&nbsp;Yuchuan Ding ,&nbsp;Abdullah Al Tekreeti ,&nbsp;Fengwu Li ,&nbsp;Yuequan Zhu ,&nbsp;Xiaokun Geng ,&nbsp;Xunming Ji","doi":"10.1016/j.brainres.2025.149920","DOIUrl":"10.1016/j.brainres.2025.149920","url":null,"abstract":"<div><h3>Background</h3><div>Parkinson’s disease (PD), the most prevalent neurodegenerative disorder, affects over 7.5 million individuals worldwide and imposes a substantial financial burden. Exercise (EXE) has demonstrated efficacy in improving motor symptoms of PD; however, its application is limited by motor symptoms such as bradykinesia, rigidity, gait instability, and fatigue, which reduce patient tolerance and adherence. This highlights the need for accessible, non-invasive alternatives with similar efficacy. Remote ischemic conditioning (RIC), a low-cost, non-invasive intervention, has shown neuroprotective effects in stroke and cognitive impairment and may offer comparable benefits without these limitations. This study evaluates the therapeutic efficacy of RIC versus EXE in a PD mouse model.</div></div><div><h3>Methods</h3><div>PD was induced in mice using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injections (30 mg/kg) for 5 days. Mice were assigned to four groups: Control, PD, EXE, and RIC. EXE involved treadmill training (30 mins, twice a day for 14 days), while RIC consisted of repeated limb ischemia–reperfusion cycles (3 occlusion–reperfusion cycles, for 14 days). Motor performance was assessed using rota-rod and open field tests. Neuroinflammatory markers, microglial activation, and oxidative stress were analyzed via immunofluorescence, ELISA, and Western blot.</div></div><div><h3>Results</h3><div>Both RIC and EXE significantly improved motor function and attenuated dopaminergic neurodegeneration. These interventions reduced α-synuclein accumulation and restored tyrosine hydroxylase (TH) expression. Additionally, both interventions suppressed microglial activation, decreased iNOS/Iba-1 and IL-1β/Iba-1 expression, and downregulated the TLR4/NF-κB pathway and associated proinflammatory cytokines (IL-1β, IL-6, TNF-α). RIC and EXE also alleviated NOX-driven oxidative stress.</div></div><div><h3>Conclusion</h3><div>RIC and EXE provide comparable neuroprotective effects in PD by suppressing TLR4-mediated neuroinflammation and oxidative damage. Given its non-invasive, low-cost nature and ease of administration, RIC may represent a promising rehabilitation strategy for patients with limited access to or tolerance for exercise-based therapies.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149920"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential contribution of light-intensity exercise-induced miR-486a-3p secretion on enhancing empathic behavior in mice: Possible involvement of brown adipose tissue","authors":"Takeru Shima,&nbsp;Keisuke Yoshii,&nbsp;Yuika Yoshikawa,&nbsp;Chiho Terashima","doi":"10.1016/j.brainres.2025.149923","DOIUrl":"10.1016/j.brainres.2025.149923","url":null,"abstract":"<div><div>Empathy plays a crucial role in the maintenance of interpersonal relationships among mammals. Remarkably, engaging in light-intensity exercise has been identified as a facilitator of empathic behavior, a phenomenon associated with the upregulation of miR-486a-3p in the insular cortex. However, it remains to cover the contribution of miR-486a-3p and the mechanisms of changing levels of that in the insular cortex with light-intensity exercise. We initially assessed the impact of light-intensity exercise (7.0 m/min, 30 min/day, five days/week for four weeks) on helping behavior, mRNA in their insular cortex, and the secretion of exosomal miR-486a-3p from their peripheral tissues. Subsequently, we explored the effects of a daily intraperitoneal injection of miR-486a-3p mimic over a two-week period on helping behavior. The intervention of light-intensity exercise, which enhanced helping behavior, resulted in elevated levels of miR-486a-3p in the insular cortex and exosomal miR-486a-3p in the plasma. Interestingly, the exercise intervention led to a marked increase in exosomal miR-486a-3p derived from brown adipose tissue, whereas no such increase was observed in exosomes originating from the gastrocnemius muscle or the liver. Moreover, the administration of mmu-miR-486a-3p mimic exhibited a similar enhancement of helping behavior in mice. Notably, both the exercise intervention and miR-486a-3p mimic treatment led to the downregulation of <em>Pten</em> mRNA and upregulation of <em>Bdnf</em> mRNA in the insular cortex. Our findings suggest that the increase in peripheral-derived miR-486a-3p, originating from the brown adipose tissue, may support empathy enhancement associated with light-intensity exercise. Additionally, miR-486a-3p may have similar effects to light-intensity exercise in relation to empathy, providing a potential approach for addressing empathy-related behaviors.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149923"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}