Behavioural Brain Research最新文献

{"title":"Differential modulation of contextual fear conditioning by orexin receptors in the dorsal hippocampus","authors":"Gabriela V.M. Oliveira ,&nbsp;Gabriela M.F. Suzuki ,&nbsp;Rafael F. Soriano ,&nbsp;Lais V. de Carvalho Alves ,&nbsp;Millena Lana C. de Carvalho ,&nbsp;Paloma M. Hernandes ,&nbsp;Carsten T. Wotjak ,&nbsp;Norberto C. Coimbra ,&nbsp;Rafael C. Almada","doi":"10.1016/j.bbr.2025.116010","DOIUrl":"10.1016/j.bbr.2025.116010","url":null,"abstract":"<div><div>The dorsal hippocampus (DH) encodes contextual memories essential for adaptive responses to environmental threats. The lateral hypothalamus (LH), a primary source of orexinergic neurons in the brain, is also involved in the modulation of defensive behaviors. Although recent research links the orexinergic system to emotional processes, its role in the DH during the organization and expression of learned fear responses remains poorly understood. This study investigates the role of orexin receptor subtypes in DH during contextual fear conditioning. Anatomical tracing techniques revealed a direct projection from the lateral hypothalamus to the DH, providing evidence for a previously unexplored pathway in fear processing. Pharmacological blockade of orexin receptor type 1 (Orx₁R) in the DH impaired the acquisition of contextual fear memories, while blockade of orexin receptor type 2 (Orx₂R) enhanced memory formation, suggesting opposing roles for these receptors in early memory processing stages. Notably, blocking either receptor before testing did not affect the expression of pre-established fear memories, suggesting that hippocampal orexin receptors are primarily involved in memory formation rather than the expression of learned fear. These findings provide insights into the contribution of the orexinergic system to emotional learning, particularly in hippocampus-dependent fear memories. These findings advance our understanding of the orexin system, specifically the Orx₁R and Orx₂R functional roles, with implications for developing therapeutic strategies targeting orexin receptors in the treatment of psychiatric disorders like anxiety and post-traumatic stress disorder, which are characterized by disrupted fear processing.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"501 ","pages":"Article 116010"},"PeriodicalIF":2.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846341","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":"Beyond the undermining effect: Extrinsic rewards preserve neural intrinsic reward","authors":"Hiroaki Ayabe ,&nbsp;Takahiko Koike ,&nbsp;Ayumi Yoshioka ,&nbsp;Satoshi Izuno ,&nbsp;Kanae Ogasawara ,&nbsp;Shohei Tsuchimoto ,&nbsp;Norihiro Sadato","doi":"10.1016/j.bbr.2025.115996","DOIUrl":"10.1016/j.bbr.2025.115996","url":null,"abstract":"<div><div>The Self-Determination Theory posits that extrinsic reward withdrawal often undermines intrinsic motivation. This undermining effect varies according to the reward category (e.g., monetary vs. praise). However, the mechanism underlying this variability remains unclear, partly because previous studies have conceptualized intrinsic motivation as a single construct without distinguishing <em>liking</em> (intrinsic value) from <em>wanting</em> (motivational drive). Failure to make this distinction may obscure the effects of rewards on each component. We hypothesized that extrinsic reward withdrawal would differentially affect intrinsic value and motivational drive. To test this hypothesis, we conducted functional magnetic resonance imaging (fMRI) on 54 participants who were randomly assigned to one of three conditions: control (no rewards), monetary reward, or social reward. Participants in the monetary and social reward groups played a stopwatch game twice, first with and then without extrinsic rewards. The control group received no extrinsic rewards during the task. We assessed intrinsic value through fMRI-measured activation of the reward system and motivational drive through voluntary engagement during the task intermission. Intrinsic value, measured by activation in predefined reward-related regions, declined in the control group but was preserved in both extrinsic reward groups after withdrawal. Thus, both monetary and social rewards were associated with preserved intrinsic value. However, intrinsic behavioral motivation declined in the monetary group but was maintained in the social group. These findings suggest that extrinsic reward withdrawal differentially influences intrinsic value and motivational drive across reward categories, thereby clarifying the variability of the undermining effect.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"501 ","pages":"Article 115996"},"PeriodicalIF":2.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762007","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":"Combining network pharmacology, machine learning, molecular docking, molecular simulation dynamics and experimental validation to explore the mechanism of Zhenwu decoction in treating major depression through TNF-α pathways","authors":"Xinyu Zhou ,&nbsp;Yan Gao ,&nbsp;Sashuang Liu ,&nbsp;Yijing Zhao ,&nbsp;Zhen Wang ,&nbsp;Dexiang Liu","doi":"10.1016/j.bbr.2025.115997","DOIUrl":"10.1016/j.bbr.2025.115997","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) is a severe psychophysiological condition characterized by cognitive decline, low energy, weight loss, insomnia, and increased suicide risk, posing a significant burden on global health. Zhenwu decoction (ZWD), a traditional Chinese medicine, has shown therapeutic potential in alleviating MDD symptoms. However, its complex composition has limited the understanding of its underlying pharmacological mechanisms. This study aimed to explore the antidepressant mechanisms of ZWD in the treatment of MDD.</div></div><div><h3>Methods</h3><div>Active compounds and potential targets of ZWD were identified through database screening and network pharmacology analysis. These targets were intersected with MDD-related genes to construct a protein–protein interaction network. Core targets were further refined using random forest algorithms. Molecular docking and molecular dynamics simulations were employed to evaluate the binding affinity and stability between key compounds and core targets. Experimental validation was conducted in a lipopolysaccharide (LPS)-induced mice model of depression using behavioral testing, measurement of inflammatory cytokines, and gene expression analysis.</div></div><div><h3>Results</h3><div>Network pharmacology and machine learning identified TNF-α signaling as key pathways in the antidepressant effects of ZWD. Enrichment analysis highlighted the involvement of Lipid and atherosclerosis, the IL-17 signaling pathway. Core targets, including PPARG, F10, AR, TNF, PIK3CG, ADH1C, and GABRA6, were predicted to mediate its effects. Molecular docking and dynamics simulations confirmed strong binding of ZWD components, especially kaempferol, to TNF-α, inhibiting its expression. In <em>vivo</em>, ZWD improved anxiety/depressive-like behaviors in LPS-treated mice, evidenced by better performance in the behavioral tests. ZWD also reduced neuroinflammation, with decreased <em>Tnf-α</em> levels, and reduced IBA-1 and GFAP staining, indicating reduced microglial and astrocyte activation. These results suggest that ZWD alleviates depression through modulation of TNF-α–mediated inflammation.</div></div><div><h3>Conclusions</h3><div>These findings suggest that ZWD exerts antidepressant effects primarily by modulating TNF-α–mediated inflammatory pathways, providing a comprehensive molecular and experimental framework supporting its clinical potential in MDD treatment.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"501 ","pages":"Article 115997"},"PeriodicalIF":2.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833156","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":"Chronic administration of berberine attenuates depressive-like behavior in rats subjected to chronic unpredictable mild stress combined with ACTH treatment: Role of nitrergic system","authors":"Sharvari Deshmukh ,&nbsp;Biru B. Dudhabhate ,&nbsp;Dipak K. Sahare ,&nbsp;Dadasaheb M. Kokare ,&nbsp;Yashashree A. Gadhikar","doi":"10.1016/j.bbr.2025.116006","DOIUrl":"10.1016/j.bbr.2025.116006","url":null,"abstract":"<div><div>Major depressive disorder (MDD) remains a significant clinical concern because of its poor response to conventional antidepressants. Berberine, an isoquinoline alkaloid of natural origin has shown promising antidepressant-like effects in preclinical models. However, the mechanism by which berberine ameliorates depressive-like behavior has not been clearly studied. Herein, we examined the effect of berberine on depression induced by chronic unpredictable mild stress (CUMS) combined with adrenocorticotropic hormone (ACTH) treatment in rats and explored the role of the nitrergic system in its mechanism. The CUMS (42 days) with ACTH (14 days) -treated rats showed decreased sucrose preference, percentage of time spent in the central area of open field tests, exploration towards the novel object in the novel object recognition test, and increased immobility time in the forced swim test. There was increased neuronal nitric oxide synthase (nNOS) immunoreactivity in the paraventricular nucleus of hypothalamus (PVN), serum corticosterone level, and reduced dopamine and serotonin levels of the hippocampus in the CUMS + ACTH-treated rats. The chronic intraperitoneal (i.p.) administration of berberine (5 mg/kg; i.p.) for 14 days to the CUMS + ACTH-treated rats reversed all these parameters. Furthermore, the administration of sodium nitroprusside (SNP; 1 mg/kg) prior to the berberine treatment in CUMS + ACTH-treated rats blocked its positive effect. The findings suggest that berberine treatment may exert its antidepressant-like and memory-enhancing effects, at least in part, by attenuating hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, potentially through the involvement of nitrergic signaling.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"501 ","pages":"Article 116006"},"PeriodicalIF":2.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809157","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":"Retraction notice to “Inhibition of glucocorticoid receptors ameliorates hypobaric hypoxia induced memory impairment in rat” [Behav. Brain Res. 240 (2013) 76–86]","authors":"Iswar Baitharu ,&nbsp;Satya Narayan Deep ,&nbsp;Vishal Jain ,&nbsp;Dipti Prasad ,&nbsp;G. Ilavazhagan","doi":"10.1016/j.bbr.2025.115980","DOIUrl":"10.1016/j.bbr.2025.115980","url":null,"abstract":"","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"500 ","pages":"Article 115980"},"PeriodicalIF":2.3,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720982","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":"Transmuscular vocal fold injury reduces frequency complexity of rat ultrasonic vocalizations","authors":"Marilla Gould ,&nbsp;Ryosuke Nakamura ,&nbsp;Wenqing Yang ,&nbsp;Ryan C. Branski ,&nbsp;Aaron M. Johnson","doi":"10.1016/j.bbr.2025.115989","DOIUrl":"10.1016/j.bbr.2025.115989","url":null,"abstract":"<div><div>Rapid and precise activation of the laryngeal musculature, particularly the thyroarytenoid (TA), is required for the production of rat ultrasonic vocalizations (USVs). Although the role of the TA in USV production has been established through denervation and excised larynx studies, how TA muscle dysfunction affects USV acoustics remains unknown. This study examined how iatrogenic, transmuscular vocal fold injury influences USV production by comparing acoustic parameters between rats receiving bilateral transmuscular vocal fold injury (including the TA muscle) versus sham surgery. Twenty adult male rats were randomly assigned to injury or sham groups and assessed at 30 or 60 days post-surgery. USVs were recorded at each timepoint (pre- and post-surgery) and analyzed for changes in principal frequency, frequency complexity (standard deviation and sinuosity), power (intensity of the USV), tonality, and duration. Injury significantly decreased USV frequency complexity and reduced the likelihood of producing frequency-modulated vocalizations in both post-surgical time groups. These findings demonstrate that while TA muscle integrity is crucial for frequency modulation, it is not necessary for basic USV production, offering new insights into the biomechanical role of the TA muscle in rat vocalization and laying the groundwork for investigating therapeutic interventions targeting laryngeal muscle function.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"500 ","pages":"Article 115989"},"PeriodicalIF":2.3,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720929","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":"Effects of intranasal oxytocin administration on histophysiology of the hippocampus in maternally separated adolescent male rats","authors":"Parisa Salehi Najafabadi ,&nbsp;Ali Shamsara ,&nbsp;Vida Mirzaie ,&nbsp;Vahid Sheibani ,&nbsp;Mahdiyeh Ahmadi ,&nbsp;Sara Joushi ,&nbsp;Mohsen Basiri","doi":"10.1016/j.bbr.2025.115983","DOIUrl":"10.1016/j.bbr.2025.115983","url":null,"abstract":"<div><div>Astrocytes are one of the glial cells of the nervous system. These cells reach their maximum number in the first two weeks after birth. Therefore, during this period they are sensitive to adverse conditions, including separation from the mother. One of the factors is the stress-modulating hormone oxytocin (OT). Adolescent male Wistar rats were used in this study. Rat pups were subjected to the MS protocol for 180 min per day from postnatal day 1–21 (postnatal day (PND)). Then, from PND 22–34, OT was administered intranasally (2 μg/μl, for 7 days). Behavioral assessments were performed on PND 35–37, we prespecified glial fibrillary acidic protein (GFAP)+ astrocyte density and morphology as the primary outcome, given astrocytes’ active roles in synaptic plasticity, stress regulation, and oxytocin signaling; the neuron degeneration ratio and p38/p-p38 expression were treated as secondary outcomes. MS did not alter locomotion; it increased anxiety-like behavior in the Zero Maze Test (ZMT) (but not in the Open Field Test (OFT)) and elevated olfactory thresholds. MS also increased the degenerated/healthy neuron ratio and p38/p-p38 protein levels, and reduced GFAP+ astrocyte density and process size in hippocampal CA1; OT partly reversed these glial/inflammatory changes without affecting the neuron degeneration ratio. These findings suggest that OT could serve as a therapeutic agent to improve some of the adverse behavioral and histological effects of MS in modern societies.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"500 ","pages":"Article 115983"},"PeriodicalIF":2.3,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720991","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":"Symptom-specific neural circuits and corresponding transcriptomic profiles in depression","authors":"Jiang Wang ,&nbsp;Chengfeng Chen ,&nbsp;Xuanyu Zhang ,&nbsp;Shiying Wang ,&nbsp;Ru Hao ,&nbsp;Yubing Xu ,&nbsp;Nan Fang ,&nbsp;Huina Teng ,&nbsp;Bin Zhang","doi":"10.1016/j.bbr.2025.115966","DOIUrl":"10.1016/j.bbr.2025.115966","url":null,"abstract":"<div><h3>Background</h3><div>Depression is a clinically heterogeneous disorder with symptom-specific neural correlates. However, systematic mapping of brain networks underlying individual symptoms remains limited, hindering deeper neurobiological understanding.</div></div><div><h3>Methods</h3><div>This study used the functional connectivity network mapping method to explore neural circuits associated with specific depressive symptoms, integrating resting-state functional magnetic resonance imaging data from multiple studies. Additionally, transcriptomic analysis was performed to examine the relationship between symptom-specific functional connectivity networks and gene expression.</div></div><div><h3>Results</h3><div>This study identified distinct neural circuits associated with specific depressive symptoms. Damage networks related to anxiety, cognitive impairment, and rumination were primarily localized within the limbic network or default mode network, while anhedonia and suicide ideation/attempt were mainly linked to the visual network. Transcriptomic analysis further identified genes linked to these networks, highlighting synaptic function, neural plasticity, and neurotransmission as key processes driven by gene expression underlying depressive symptoms. Functional enrichment analysis also revealed distinct neurobiological profiles for different symptoms, including specific immune-related processes for cognitive impairment and neurodevelopmental features for sleep disturbance.</div></div><div><h3>Conclusions</h3><div>This study identified neural circuits associated with specific depressive symptoms and their associated brain gene expression. The findings revealed symptom-specific damage networks, highlighting key biological processes including synaptic signaling, neural plasticity, and neurotransmission. Additionally, distinct neurobiological features were observed, including immune-related processes linked to cognitive impairment and neurodevelopmental characteristics related to sleep disturbance. These findings may provide new insights into the neurobiological mechanisms of depression.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"500 ","pages":"Article 115966"},"PeriodicalIF":2.3,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145628148","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":"Resveratrol prevents arsenic-induced depression-like phenotypes via modulation of BDNF signaling","authors":"Mohaddeseh Kharazmi ,&nbsp;Tayyebeh Khalili ,&nbsp;Marzieh Dehghan-Shasaltaneh ,&nbsp;Abbas Bahari ,&nbsp;Mohaddeseh Ebrahimi-Ghiri","doi":"10.1016/j.bbr.2025.115988","DOIUrl":"10.1016/j.bbr.2025.115988","url":null,"abstract":"<div><div>Growing evidence suggests that resveratrol possesses neuroprotective properties against arsenic toxicity. This study investigated whether resveratrol could ameliorate arsenic-induced depression-like behaviors in male Naval Medical Research Institute (NMRI) mice and explored potential molecular mechanisms. Mice were exposed to arsenic (50 mg/L in drinking water) for 4 weeks and treated with resveratrol (10 or 20 mg/kg). Behavioral assessments included the hole-board test (HBT) for exploratory behavior, and the sucrose splash test (SST), tail suspension test (TST), and forced swim test (FST) for depression-like behaviors. The mRNA levels of <em>Bdnf</em>, <em>Creb1</em>, and <em>Dvl1</em> in the brain were analyzed by qRT-PCR. Arsenic exposure induced significant depression-like behaviors, characterized by decreased grooming in SST and increased immobility in TST and FST. Resveratrol treatment prevented these behavioral alterations and exhibited intrinsic antidepressant effects in naïve mice, with dose-dependent reductions in immobility time (FST) and increased grooming (SST). Notably, resveratrol (20 mg/kg) enhanced rearing frequency in naïve mice and decreased it in the arsenic-treated mice. At the molecular level, arsenic downregulated <em>Bdnf</em> expression, while resveratrol restored its levels. In contrast, no significant changes in <em>Creb1</em> and <em>Dvl1</em> expression were observed. These findings indicate that resveratrol mitigates arsenic-induced depression-like behaviors primarily through the modulation of <em>Bdnf</em>-dependent pathways, independent of <em>Creb1</em> and <em>Dvl1</em>. These results position resveratrol as a potential antidepressant and underscore its therapeutic promise for mood disorders associated with environmental toxicant exposure.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"500 ","pages":"Article 115988"},"PeriodicalIF":2.3,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740721","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":"Advanced age and lipopolysaccharide influence behavioral and neurodegenerative features in LRRK2 G2019S knock-in mice","authors":"Anuroopa Dinesh,&nbsp;Teresa Fortin,&nbsp;Hongyu Sun,&nbsp;Shawn Hayley","doi":"10.1016/j.bbr.2025.115970","DOIUrl":"10.1016/j.bbr.2025.115970","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is a progressive neurodegenerative disease thought to arise from the collective impact of advancing age, genetic vulnerabilities and possibly exposure to environmental toxicants. The LRRK2 point mutation, G2019S, is the most common genetic link with PD and has been reported to have age-dependent effects in rodents, as well as being linked to neuroinflammatory processes. Accordingly, the objective of the current study was to elucidate the interactive effects of advanced age and activation of the immune system using the bacterial endotoxin, lipopolysaccharide (LPS), in G2019S knockin mice and their wild type littermates. Adult young (3–4 months) and aged (9–12 months) mice were administered five intraperitoneal injections of 250 ug/kg of LPS (or saline) every alternate day. Significant interactions between age, genotype and injection were evident across several behavioral outcomes. In fact, the aged G2019S mice were more vulnerable to the LPS injections in terms of the sickness response, deficits in nest building behaviors, weight loss, along with protracted reductions in home cage motor activity. These mice also exhibited alterations of SNc inflammatory microglia proteins (WAVE2 and CXCR1) and had the greatest loss of substantia nigra dopamine neurons, which is consistent with a PD-like phenotype. Taken together, our data suggest that the LRRK2 G2019S mutation might be a general regulator of aging and inflammatory processes that are important for neurodegeneration, together with motor and non-motor symptoms.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"500 ","pages":"Article 115970"},"PeriodicalIF":2.3,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145686738","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}