Behavioural Brain Research最新文献

{"title":"Sex differences in 6-OHDA lesioned rats in a preclinical model for Parkinson’s disease","authors":"Raquel de Souza Lima ,&nbsp;Jaime Fornaguera","doi":"10.1016/j.bbr.2025.115642","DOIUrl":"10.1016/j.bbr.2025.115642","url":null,"abstract":"<div><div>Although Parkinson’s disease (PD) was first described in 1817, its etiology remains unclear. The primary neurotransmitter system affected in PD is the nigrostriatal dopaminergic pathway, whose dysfunction leads to the hallmark motor symptoms of the disease. These motor symptoms typically emerge only after approximately 80 % of dopaminergic neurons are lost, complicating early detection and intervention. For this reason, it is important to know more about the stages prior to the appearance of symptoms that could represent the progression of the disease. Additionally, substantial evidence suggests sex differences in PD prevalence and progression, with men more frequently affected than women. However, most preclinical studies using animal models of PD have been conducted exclusively on males, limiting our understanding of neurochemical and behavioral differences between sexes, particularly under moderate dopaminergic lesions. To address this, we used the unilateral 6-hydroxydopamine (6-OHDA) model of PD, inducing moderate lesions in the substantia nigra pars compacta (SNpc) to investigate sex-specific variations. Our study revealed distinct neurochemical and behavioral profiles in male and female animals, including sex-specific responses to amphetamine and apomorphine challenges. These pharmacological tests highlighted contrasting patterns in asymmetric and symmetric behaviors between sexes. Moreover, we considered individual variability often overlooked in animal models, which could provide critical insights into resilience or susceptibility to dopaminergic loss. These findings underscore the importance of incorporating sex as a biological variable in PD research to better understand the disease’s underlying mechanisms and to improve strategies for early diagnosis and therapeutic intervention.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"490 ","pages":"Article 115642"},"PeriodicalIF":2.6,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101159","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":"Impact of temporal food restriction on sleep behavior and physiology of redheaded bunting","authors":"Anupama Yadav ,&nbsp;Vaibhav Vaish ,&nbsp;Sangeeta Rani","doi":"10.1016/j.bbr.2025.115603","DOIUrl":"10.1016/j.bbr.2025.115603","url":null,"abstract":"<div><div>Photic cues are the epicenter of regulating different biological rhythms, however non-photic cues like food and temperature also play a pivotal role in governing the same. The present study investigated the role of temporal food restriction on sleep behavior and physiology of redheaded bunting. Birds (N = 20 each for male and female) were divided into four groups on the basis of availability of food; group I (ad-libitum food; Control), group II (evening restriction group; ER), group III (morning restriction group; MR) and group IV (unpredictable group; UR). The food restricted groups showed starvation induced hyperactivity which influenced the temporal orientation of different sleep behaviors during night. Morning food restricted group showed abundance of back sleep, irrespective of sex. However, sleep duration was found unmoved by the restriction protocol. Morning food restriction significantly reduced body mass, food intake and liver weight in male birds, but females were found unresponsive to these changes. To understand the molecular underpinning of the physiological response, we checked relative mRNA expression of <em>npy</em> and <em>vip</em> in gut and hypothalamus of birds. <em>npy</em> expression was found elevated with respect to food restriction both in gut and hypothalamus. Moreover, hypothalamic <em>nos1</em> and <em>chrm3</em> were also evaluated as markers of sleep and wakefulness respectively. Food restriction resulted in elevated expression of <em>chrm3</em> when compared with control. Thus, the present study highlights the role of temporal food restriction on sleep behavior and physiology of birds.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"491 ","pages":"Article 115603"},"PeriodicalIF":2.6,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101235","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":"Maternal separation after postnatal day 10 induces increase in depression-like behavior with decrease in hippocampal dendritic spines, but no change in anxiety-like behavior in male rats","authors":"Kento Takabayashi ,&nbsp;Yuki Kajita ,&nbsp;Hajime Mushiake","doi":"10.1016/j.bbr.2025.115617","DOIUrl":"10.1016/j.bbr.2025.115617","url":null,"abstract":"<div><div>Neurodevelopment has a “sensitive period” during which the brain is highly sensitive to experience. In this study, we used maternal separation (MS) models of male Long-Evans rats to examine whether sensitivity to stress changes after postnatal day (PND) 10, when dendritic spine density begins to increase rapidly in the CA (Cornu Ammonis)1 region of the hippocampus.</div><div>We assigned littermates to three groups: early maternal separation group (EMS: MS during PND 1–9), late maternal separation group (LMS: MS during PND 10–20), and control group. During adulthood (PND 56–75, which strictly corresponds to young adulthood), LMS showed increased depression-like behaviors and decreased dendritic spine density in the CA1 hippocampal region; however, EMS did not show any such changes.</div><div>Accordingly, littermates at PND 10–20 have a greater vulnerability to MS than those at PND 1–9. These findings suggest that dendritic spine formation in the hippocampus is an important factor in determining sensitivity to MS.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"490 ","pages":"Article 115617"},"PeriodicalIF":2.6,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089735","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":"Altered c-Fos expression following alcohol intake in discrete brain regions of galanin 3 receptor knockout mice","authors":"Shannyn G. Genders ,&nbsp;Ross O’Shea ,&nbsp;Susanne Brunner ,&nbsp;Barbara Kofler ,&nbsp;Matthew W. Hale ,&nbsp;Maarten van den Buuse ,&nbsp;Elvan Djouma","doi":"10.1016/j.bbr.2025.115640","DOIUrl":"10.1016/j.bbr.2025.115640","url":null,"abstract":"<div><div>The aim of this study was to investigate the brain regions involved in the role of galanin (GAL) and specifically <em>GAL</em>_<em>3</em>-receptors (<em>GAL</em>₃) in alcohol intake. <em>GAL</em>_<em>3</em>-KO mice displayed an alcohol-preferring phenotype in a two-bottle, free choice paradigm. In contrast, no genotype differences in ethanol intake were observed in a Drinking In the Dark (DID) model, highlighting the differential involvement of brain GAL activity depending on the experimental model of alcohol consumption. Blood ethanol concentrations were approximately 10 % lower in <em>GAL</em>_<em>3</em>-KO mice compared to wildtype (WT) following DID. WT mice drinking ethanol had significantly increased numbers of c-Fos immunoreactive (ir) neurons in the rostral prelimbic (PrL) and infralimbic (IL) regions of the prefrontal cortex (PFC) and decreased numbers of ir neurons in the CA1 region of the dorsal hippocampus (dHIP) compared to water drinking WT littermates, but these effects of ethanol were absent in <em>GAL</em>_<em>3</em>-KO mice. Water drinking <em>GAL</em>_<em>3</em>-KO mice furthermore had significantly increased numbers of c-Fos ir neurons compared to water drinking WT mice in the rostral PrL as well as the CA3 region of the dHIP. In the core and shell subregions of the nucleus accumbens (NAc), or in the paraventricular nucleus of the hypothalamus (PVN) or basolateral amygdala, there were no changes in the number of c-Fos ir cells or any involvement of <em>GAL</em>_<em>3</em> genotype. These findings support a role of <em>GAL</em>_<em>3</em>-receptors in the effects of alcohol and implicate discrete brain regions involved in this interaction.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"490 ","pages":"Article 115640"},"PeriodicalIF":2.6,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101193","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":"Disrupting fear memory reconsolidation in individuals with fear of spiders with cTBS: A Proof-of-Concept Study","authors":"M.J. Herrmann ,&nbsp;D. Schaub ,&nbsp;G.C. Ziegler ,&nbsp;A. Mühlberger ,&nbsp;L.M. Cybinski","doi":"10.1016/j.bbr.2025.115644","DOIUrl":"10.1016/j.bbr.2025.115644","url":null,"abstract":"<div><div>Anxiety disorders can be effectively treated with both cognitive behavioural therapy and psychopharmacological interventions. However, only 50 % of patients demonstrate significant benefits from these approaches. Therefore, investigating strategies to improve treatment effectiveness or develop novel therapeutic approaches remains an important research objective. Current therapeutic modalities may leave the original fear memory intact, potentially leading to symptom recurrence over time. In contrast, the disruption of reconsolidation processes can facilitate permanent modifications to fear memory, resulting in a reduced risk of relapse after psychotherapy. Recent laboratory studies have shown that the reconsolidation of experimentally induced fear can be effectively disrupted by repetitive transcranial magnetic stimulation (rTMS) and significantly prevents the return of fear. In this study, we translated these results to participants with elevated fear of spiders. 34 participants with spider fear were randomly assigned to a verum or a placebo intervention using continuous theta-burst stimulation (80 % of resting motor threshold) applied over the right dorsolateral prefrontal cortex ten minutes after the reactivation (3 min confrontation with a living tarantula) of the spider fear memory. The ANOVA for the primary outcome (Spider Phobia Questionnaire, SPQ) resulted in a significant effect of time, but no significant interaction of time and treatment group. Notably, exploratory analyses revealed a significant correlation between stimulation intensity in the verum group and the reduction in spider fear. This association suggest that rTMS-induced disruptions of reconsolidation may serve as a viable therapeutic option for anxiety disorders; however, further research is needed to delineate the optimal parameters for such interventions.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"491 ","pages":"Article 115644"},"PeriodicalIF":2.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092547","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":"Hepatic encephalopathy induces anxiety and depression-like behaviors, cytokine dysfunction, BDNF down-regulation and neuropathological changes in mice","authors":"Luiza Cioglia Dias Lima ,&nbsp;Bruna da Silva Oliveira ,&nbsp;Isadora Sofia Souza Nunes ,&nbsp;Thiago Henrique Caldeira de Oliveira ,&nbsp;Eliana Cristina de Brito Toscano ,&nbsp;Caroline Amaral Machado ,&nbsp;Reane Fonseca Martins ,&nbsp;Juliana Lemos Del Sarto ,&nbsp;Érica Leandro Marciano Vieira ,&nbsp;Gustavo Batista Menezes ,&nbsp;Ana Cristina Simões e Silva ,&nbsp;Antônio Lúcio Teixeira ,&nbsp;Aline Silva de Miranda ,&nbsp;Milene Alvarenga Rachid","doi":"10.1016/j.bbr.2025.115643","DOIUrl":"10.1016/j.bbr.2025.115643","url":null,"abstract":"<div><div>Psychiatric disorders, such as disturbance of sleep, irritability, anxiety and depressive symptoms have been reported in patients with hepatic encephalopathy (HE). However, these neuropsychiatric disorders in patients with HE remains largely unknown. The present study aimed to explore if acute HE lead to anxiety and depression-like behaviors and alterations in the levels of inflammatory cytokines, chemokines and neurotrophic levels in the pre-frontal cortex, striatum and hippocampus as well as neuropathological changes in mice. HE was induced by an intraperitoneal single dose of 600 mg/kg of thioacetamide (TAA). Behavioral symptoms were assessed by open field, elevated plus maze and forced swimming tests. Measurements of cytokines [tumor necrosis factor (TNF), interferon-gamma (IFN-γ), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 12p70 (IL-12 p70), interleukin-1-beta (IL-1β)], chemokines [chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-X-C motif) ligand 1 (CXCL1), C-X3-C motif chemokine ligand 1 (CX3CL1)] and neurotrophic factors [brain-derived neurotrophic factor (BDNF), glial cell line derived neurotrophic factor (GDNF), nerve growth factor (NGF)] from pre-frontal cortex, striatum and hippocampus were obtained by CBA and ELISA assays. Liver dysfunction and injury were evaluated by serum liver enzymes and histopathological analysis. We evaluated immunohistochemistry for GFAP and Iba-1 at different brain regions. TAA induced liver necrosis, inflammation and increased serum levels of liver enzymes and myeloperoxidase (MPO), N-acetylglucosaminidase (NAG) activities. Seven days post induction, mice with HE developed anxiety and depression-like behaviors and exhibited areas of astrogliosis and reactive microglia in the cerebral cortex and hippocampus. Additionally, HE animals showed lower levels of BDNF and higher concentrations of IL-1β in the pre-frontal cortex and lower levels of IFN-γ and IL-6 in the hippocampus. Our data revealed for the first time that acute hepatic encephalopathy causes anxiety and depression-like behaviors, cytokine dysfunction, BDNF down-regulation and neuropathological changes in mice.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"492 ","pages":"Article 115643"},"PeriodicalIF":2.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092628","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":"Differences in frontal cortical brain function between individuals suffering from pathological mental fatigue following acquired brain injury and healthy individuals","authors":"Gustaf Glavå ,&nbsp;Simon Skau ,&nbsp;Martin Lövdén ,&nbsp;Birgitta Johansson","doi":"10.1016/j.bbr.2025.115631","DOIUrl":"10.1016/j.bbr.2025.115631","url":null,"abstract":"<div><div>Pathological mental fatigue (PMF) is a common health concern after acquired brain injuries, with tens of millions affected globally each year. Neuroimaging methods show promising results for establishing associations between PMF and brain function. The aim of this study was to investigate whether and how neural functional activity and connectivity differ during rest and cognitive tasks between people with PMF and healthy controls. Twenty participants suffering from PMF after an acquired brain injury (ABI; stroke or traumatic brain injury) and 19 healthy controls were recruited and underwent cognitive tests and functional near infrared spectroscopy (fNIRS) assessments. The results show that the PMF group and controls exhibited different functional brain activation in the frontal cortex, concerning both neural connectivity and activity. More specifically, the PMF group showed higher Global Efficiency and lower Modularity during resting state and when performing the cognitive tasks Digit Symbol Coding and Symbol Search. The groups also differed in peak oxygenated hemoglobin during the BASE task, with lower oxygenation in the PMF group. In addition, the PMF group was significantly slower than the control group in both neutral and incongruent Stroop trials. However, no group differences were observed in neural activity during the Stroop task, and nor were there differences in reactivity or proactivity as measured using the AX-CPT test. This study has developed the knowledge on the brain correlates of PMF. Future studies should explore the theoretical and practical implications of these results.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"490 ","pages":"Article 115631"},"PeriodicalIF":2.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071814","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":"Enhanced analgesia: Synergistic effects of melatonin and tramadol on acute thermal nociception in Wistar rats via tail-flick and hot-plate tests","authors":"Emine Çakırgöz ,&nbsp;Gülçin Durdağı ,&nbsp;Eser Öz Oyar","doi":"10.1016/j.bbr.2025.115641","DOIUrl":"10.1016/j.bbr.2025.115641","url":null,"abstract":"<div><h3>Background/aim</h3><div>The aim of the study is to evaluate the antinociceptive effects of Tramadol+Melatonin [using Hot-plate (HP) and Tail-flick (TF) tests] at the behavioral level and to investigate its effects on motor coordination (using the Rotarod test) in acute pain.</div></div><div><h3>Materials and methods</h3><div>Thirty-two male Wistar albino rats, 8 weeks old and weighing 250–300 g, were used. The rats were randomly divided into four groups of eight animals each [Control, Tramadol (20 mg/kg), Melatonin (120 mg/kg), and Tramadol+Melatonin (20 mg/kg+120 mg/kg)]. The rats were trained to walk on the rotarod for 3 days prior to the experiment. Thermal acute nociception was assessed in rats using two TF tests and one HP test. Measurements were recorded before drug administration (baseline) and at 15, 30, 60, 90, and 120 minutes post-administration.</div></div><div><h3>Results</h3><div>Significantly higher values were obtained in both the HP and TF tests compared to the control, Melatonin, and Tramadol groups at various time points. In the Rotarod test, the baseline values of the Melatonin and Tramadol+Melatonin groups were significantly longer at certain post-administration time points.</div></div><div><h3>Conclusion</h3><div>The findings indicate a potential synergistic interaction between melatonin and tramadol, as evidenced by improved pain sensitivity thresholds. These results underscore the necessity for further clinical investigations to elucidate the therapeutic advantages and underlying mechanisms of this combination. Such research could significantly contribute to the development of more efficacious pain management protocols.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"490 ","pages":"Article 115641"},"PeriodicalIF":2.6,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935885","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":"Impaired cognitive function and altered dendritic morphology of hippocampal neurons in a mouse model of fetal alcohol spectrum disorder","authors":"Yu Cai ,&nbsp;Jia-Chun Wu ,&nbsp;Ying Huang ,&nbsp;Xue-Feng Yu ,&nbsp;Fu-He Liu ,&nbsp;Zi-Wei Chen ,&nbsp;Da-Peng Gao","doi":"10.1016/j.bbr.2025.115633","DOIUrl":"10.1016/j.bbr.2025.115633","url":null,"abstract":"<div><div>Prenatal ethanol exposure is a leading preventable cause of neurodevelopmental disability, clinically categorized under fetal alcohol spectrum disorders (FASD). This study explores how developmental alcohol exposure affects the dendritic morphology of hippocampal pyramidal neurons, focusing on the actin cytoskeleton's dynamics essential for neuronal structure and synaptic function. Within this context, we hypothesized that developmental alcohol exposure disrupts actin cytoskeleton dynamics, leading to cognitive deficits and dendritic remodeling in the hippocampus. Neonatal mice (C57BL/6 J) were administered ethanol (5.0 g/kg) intraperitoneally from postnatal day 2–8, establishing a third trimester-equivalent alcohol exposure FASD model. At postnatal day 28, cognitive performance was evaluated using novel location recognition (NLR), novel object recognition (NOR), and the Morris water maze (MWM). Golgi staining assessed dendritic morphology in the hippocampal CA1 region, and the ratio of polymerized (F-actin) to globular actin (G-actin) was measured using a biochemical assay. The results revealed that developmental alcohol exposure significantly impaired recognition and spatial memory, as evidenced by decreased performances in the NOR and MWM tests across both sexes. Golgi staining revealed reduced dendritic arborization complexity and spine density in the CA1 region of the hippocampal pyramidal neurons of both male and female juvenile mice. Biochemical analyses further revealed decresed hipocampal F-actin/G-actin ratios and decreased levels of polymerized F-actin in both sexes. These findings underscore the critical role of cytoskeletal integrity in cognitive development and highlight potential targets for therapeutic intervention in FASD.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"490 ","pages":"Article 115633"},"PeriodicalIF":2.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942440","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":"Serotonin mitigates depression in a rotenone-induced mouse Parkinson’s disease model by inhibiting hippocampal neuronal pyroptosis and neuroinflammation","authors":"Jian Wang ,&nbsp;Hong Zhang","doi":"10.1016/j.bbr.2025.115620","DOIUrl":"10.1016/j.bbr.2025.115620","url":null,"abstract":"<div><div>Depression in Parkinson’s disease (dPD) is a prevalent comorbidity significantly impairing patients’ quality of life. Emerging evidence highlights the pivotal role of neuroinflammation in dPD pathogenesis, particularly the interaction between neuronal pyroptosis and microglial polarization. Serotonin (5-hydroxytryptamine, 5-HT) has been implicated in mood regulation and neuroinflammatory processes, yet its role in modulating pyroptosis and microglial polarization remains unclear. Therefore, this study aimed to investigate neuronal pyroptosis and microglial polarization in dPD pathogenesis and explore the regulation of 5-HT on these processes. A C57BL/6 mouse model of dPD was established using injected intraperitoneally of rotenone to observe changes in body weight, sucrose preference, and exercise time. ELISA and Western blotting were used to detect the expression of relevant proteins and cytokines in the hippocampus. Co-culture experiments with HT22 and BV2 cells were conducted to explore the effect of 5-HT on neuronal pyroptosis and microglial polarization. Rotenone-induced dPD in mice led to reduced body weight, sucrose preference, and activity, accompanied by upregulation of pyroptosis markers (NLRP1, N-GSDMD, Cleaved-caspase-1) and increased M1 microglial polarization. Treatment with 5-HT and the pyroptosis inhibitor Pep19–2.5 reversed these changes, mitigating neuronal pyroptosis and shifting microglial polarization towards a less inflammatory profile. In vitro, 5-HTP suppressed LPS-induced neuronal pyroptosis, reducing TNF-α, IL-1β, IL-18 levels and oxidative stress while preserving microglial viability. The 5-HT inhibitor Scopolamine abolished these effects. Neuronal pyroptosis and M1 microglial polarization contribute critically to dPD pathogenesis. By inhibiting these processes, 5-HT emerges as a promising therapeutic target for managing dPD, offering new insights into its treatment mechanisms.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"490 ","pages":"Article 115620"},"PeriodicalIF":2.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942360","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}