{"title":"Motor expertise shapes crossmodal and modality-specific action representations in table tennis players.","authors":"Hong Mou, Likai Liu, Yingying Wang","doi":"10.1186/s12993-025-00296-9","DOIUrl":"10.1186/s12993-025-00296-9","url":null,"abstract":"<p><p>Multivariate neuroimaging studies have shown a functional dissociation between the temporal and frontoparietal cortices in action representation. However, it remains unclear to what extent this specificity is modulated by motor experience. To address this question, we employed functional magnetic resonance imaging-based multivoxel pattern analysis (MVPA). Neural activation patterns were compared between professional table tennis players (experts) and novices during the passive observation of action videos and the reading of corresponding action-related sentences. Specifically, to identify brain regions that decode perceptual-motor information, classifiers were trained and tested within the same stimulus modality (video or sentence). To identify brain regions supporting conceptual-level action decoding, classifiers trained on video stimuli were tested on sentence stimuli, and vice versa. The results revealed that, in experts, the left lateral posterior temporal cortex (LPTC) and anterior temporal lobe (ATL) supported crossmodal action representations, whereas the left superior parietal lobule (SPL) and precentral gyrus (PreCG) exhibited modality-specific representations, particularly in response to video-based stimuli. In novices, only the PreCG showed modality-specific representations for video stimuli. These findings suggest a functional dissociation across brain regions, with the temporal cortex involved in conceptual-level representations of actions andthe SPL associated with processing perceptual-motor features. While such representations were more prominent in experts for familiar actions, the PreCG showed modality-specific representations regardless of group. These results highlight potential group-level differences in the neural encoding of action-related information, which may reflect the influence of task familiarity or prior sensorimotor experience.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"34"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Georges Naim, Sabah Znait, Nour Sherri, Elias A Rahal, Margret Shirinian
{"title":"Disruption of circadian rhythms and behavior in Drosophila melanogaster induced by Epstein-Barr virus: insights into viral infections and host physiology.","authors":"Georges Naim, Sabah Znait, Nour Sherri, Elias A Rahal, Margret Shirinian","doi":"10.1186/s12993-025-00286-x","DOIUrl":"10.1186/s12993-025-00286-x","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) has been extensively studied for its associations with autoimmune disorders, various cancers, and neurological diseases. Emerging evidence also links EBV to behavioral and neurophysiological disruptions, potentially mediated through interactions with host's immune and circadian systems. In this study, we investigated the effects of EBV and its DNA on the behavior of Drosophila melanogaster by examining its lifespan, activity, sleep, and circadian rhythms. Both EBV viral particles and EBV DNA showed distinct effects in terms of behavior and survival. Circadian function analysis showed disruptions in several circadian parameters in EBV-injected flies, whereas EBV DNA-injected flies displayed defects in sleep behavior. Our findings suggest that EBV may impact circadian mechanisms, thereby enhancing our understanding of the effects of viral infections on circadian and behavioral systems and establishing Drosophila as a valuable model for future studies on EBV and host physiology.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"33"},"PeriodicalIF":3.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Copper loading may affect rat neurobehaviour by impairing mitochondria-associated endoplasmic reticulum membranes in hippocampal neurons.","authors":"Zhengzhe Sun, Shan Jin, Xiang Fang, Wenming Yang, Huaizhen Chen","doi":"10.1186/s12993-025-00277-y","DOIUrl":"10.1186/s12993-025-00277-y","url":null,"abstract":"<p><strong>Background: </strong>To observe the effects of copper sulfate (CuSO<sub>4</sub>)-induced copper loading on neurobehaviour, mitochondria-associated endoplasmic reticulum membranes (MAMs) and related regulatory proteins in the hippocampal CA1 region of Sprague-Dawley (SD) rats.</p><p><strong>Methods: </strong>Forty SD male rats were randomly divided into control and copper loading groups of 20 rats each. The control group rats were fed with normal feed and water; rats in the copper loading group were fed high copper feed (containing 1g/kg of CuSO<sub>4</sub>) and CuSO<sub>4</sub> deionized water (concentration of 0.185%). After 12 weeks of rearing, the morris water maze (MWM) task and novel object recognition (NOR) test were conducted to compare the neurobehavioral characteristics of the two groups of rats. Morphological changes of neuronal MAMs in the hippocampal CA1 region of copper-loaded rats were observed using a transmission electron microscope (TEM) and immunofluorescence double-labelling techniques. Western-blot analysis was used to detect the expression of MAMs proteins VDAC1, IP3R, GRP75 and Mfn2.</p><p><strong>Results: </strong>The results revealed that rats in the copper-loading group had significantly prolonged escape latency and reduced number of platform crossings in the MWM task (p < 0.01). The percentage of novel objects explored (also known as the Discrimination Ratio, DR) and the discrimination index (DI) were significantly reduced in the NOR test (p < 0.01). In addition, electron microscopy shows increased disruption of neuronal endoplasmic reticulum (ER)-mitochondrion coupling in the hippocampal CA1 region of rats in the copper-loading group (p < 0.05), and the percentage of MAMs in mitochondrial circumference decreased (p < 0.05), the colocalization coefficients between the ER and mitochondria was significantly reduced (p < 0.05). Moreover, the protein expression levels of VDAC1, IP3R, and GRP75 in rat hippocampal tissue were detected to be significantly increased (p < 0.01), while the protein expression level of Mfn2 was significantly decreased (p < 0.01).</p><p><strong>Conclusions: </strong>In this study, it is speculated that the neurobehavioral changes in rats may be related to the increased expression levels of the MAMs proteins VDAC1, IP3R, and GRP75, the reduced expression level of Mfn2, and the disruption of the structural integrity of MAMs in the hippocampal CA1 region of rats caused by copper loading.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"32"},"PeriodicalIF":3.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"PHLPP1 deficiency alleviates dopaminergic neurodegeneration and represses neuroinflammation in Parkinson's disease.","authors":"Zhilin Chen, Yuan Liu, Jinyue Zhao, Xin Zhou, Yudi Han, Zikai Zhou, Huazheng Liang, Yong Bi","doi":"10.1186/s12993-025-00293-y","DOIUrl":"10.1186/s12993-025-00293-y","url":null,"abstract":"<p><strong>Background: </strong>Pleckstrin homology (PH) domain leucine-rich repeat protein phosphatases (PHLPP) has been associated with several neurodegenerative diseases, however, few studies have investigated the role of PHLPP in Parkinson's disease (PD). The present study aimed to answer this question through establishing a Parkinson's disease (PD) model using the Phlpp1-/- and wild-type (WT) mice and testing their behavioral as well as molecular changes.</p><p><strong>Methods: </strong>MPTP was intraperitoneal injected into mice to generate a PD model. Neurobehavioral parameters, protein expression and inflammatory cytokines release were measured by the open filed test, the pole test, immunohistochemistry, immunoblotting, immunoprecipitation, and quantitative reverse transcription PCR.</p><p><strong>Results: </strong>MPTP-induced neurobehavioral deficits were more significantly ameliorated in PHLPP-KO-MPTP mice compared to WT-MPTP mice. The survival rate of TH<sup>+</sup> neurons in the PHLPP-KO-MPTP group was higher than that in the WT-MPTP group (66% vs. 38%). Additionally, PHLPP1 knockout in KO-MPTP mice markedly reduced levels of IL-1β, IL-6, TNF-α, and iNOS, and increased levels of TGF-β compared to those of WT-MPTP mice. Furthermore, PHLPP1 was found to bind to NLRP3 and that PHLPP1 knockout inhibited MPTP-induced expression of IL-1β and caspase-1 in substantia nigra of PD model mice.</p><p><strong>Conclusion: </strong>Our results demonstrates that PHLPP1 knockout in PD model is positively associated with the survival of TH + neurons by suppressing inflammatory response in substantia nigra, suggesting that PHLPP1 plays a critical role in the development of PD.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"29"},"PeriodicalIF":3.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Representation of top-down versus bottom-up attention in the right dorsolateral prefrontal cortex and superior parietal lobule.","authors":"Qiuzhu Zhang, Wenjuan Li, Tingting Zhang, Ronglong Xiong, Junjun Zhang, Zhenlan Jin, Ling Li","doi":"10.1186/s12993-025-00297-8","DOIUrl":"10.1186/s12993-025-00297-8","url":null,"abstract":"<p><strong>Background: </strong>Visual selective attention can be categorized into top-down (goal-driven) and bottom-up (stimulus-driven) attention, with the fronto-parietal network serving as the primary neural substrate. However, fewer studies have focused on the specific roles of the right dorsolateral prefrontal cortex (DLPFC) and superior parietal lobule (SPL) in top-down and bottom-up attention. This study aimed to investigate the activity and connectivity of the right DLPFC and SPL in top-down and bottom-up attention.</p><p><strong>Methods: </strong>Visual pop-out task mainly induces bottom-up attention, while the visual search task mainly induces top-down attention. Fifty-four participants completed the pop-out and search tasks during functional magnetic resonance imaging (fMRI) scanning. We used univariate analyses, multivariate pattern analyses (MVPA), and generalized psychophysiological interaction (gPPI) to assess activity and functional connectivity.</p><p><strong>Results: </strong>Univariate analyses revealed stronger activation in the right DLPFC and SPL during the search > pop-out condition. The activation of the DLPFC was driven by its deactivation in the pop-out task, whereas the SPL showed significant activation in both tasks. MVPA demonstrated that activation patterns in the right DLPFC and SPL could distinguish between the pop-out and search tasks above chance level (0.5), with the right SPL exhibiting higher classification accuracy. The gPPI analyses showed that higher functional connectivity between the two seeds (right DLPFC and SPL) and bilateral precentral gyrus, left SPL, and right insula.</p><p><strong>Conclusions: </strong>These results indicate that the right DLPFC and SPL showed stronger activity and connectivity under top-down versus bottom-up attention, allowing for neural representation of visual selective attention. This study provides evidence for understanding the role of the fronto-parietal network in visual selective attention.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"31"},"PeriodicalIF":3.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Isoacteoside alleviates LPS-induced depressive-like behaviors in mice by inhibiting neuroinflammation through regulating microglial polarization and oxidative stress.","authors":"Jiajia Bi, Hui Zhang, Jia Wei, Xuhui Huang, Yuqian Dong, Yifan Dong, Yiming Xie, Ranran Li, Sujuan Chen, Zihan Zhao, Binfeng Cheng","doi":"10.1186/s12993-025-00298-7","DOIUrl":"10.1186/s12993-025-00298-7","url":null,"abstract":"<p><p>Recent studies have demonstrated a close association between neuroinflammation and depression. Isoacteoside (ISO) has recently been reported to exhibit anti-inflammatory properties. However, the effects of ISO on neuroinflammation-induced depression and its underlying mechanisms have not been fully elucidated. This study aimed to investigate the mechanism of ISO on neuroinflammation-induced depression from both in vivo and in vitro aspects. In the in vivo experiments, lipopolysaccharide (LPS) was used to induce depressive-like behavior in adult male C57BL/6J mice, which were subsequently detected using the open field test (OFT), forced swim test (FST), and tail suspension test (TST). Quantitative real-time polymerase chain reaction (qPCR) and western blot were employed to measure the expression of inflammatory and polarization markers, as well as related proteins. Immunofluorescence staining was used to detect the expression of glial cell markers. For the in vitro experiments, BV2 and SH-SY5Y cells were selected and treated with LPS for subsequent analysis. The results indicated that mice treated with LPS exhibited depressive-like behaviors, accompanied by significant levels of neuroinflammation and oxidative stress, all of which were effectively reduced by ISO treatment. Furthermore, ISO facilitated the normalization of microglial polarization from the M1 to M2 phenotype, reduced the expression of ionized calcium-binding adaptor 1 (Iba1) and glial fibrillary acidic protein (GFAP), and modulated the CREB/BDNF signaling pathway. These findings suggest that ISO has an ameliorative effect on LPS-induced depressive-like behavior in mice, which may be achieved by attenuating neuroinflammation and oxidative stress as well as modulating the phenotype of microglia.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"30"},"PeriodicalIF":3.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction: Spectral tuning and after‑effects in neural entrainment.","authors":"Maëlan Q Menetrey, David Pascucci","doi":"10.1186/s12993-025-00295-w","DOIUrl":"10.1186/s12993-025-00295-w","url":null,"abstract":"","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"28"},"PeriodicalIF":3.3,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jianing Yang, Li Li, Yanan Xu, Yuguang Guan, Xiaoli Li
{"title":"TREK-1 and epilepsy: regulating the balance of K<sup>+</sup> and the glutamate release in astrocyte-neuron interactions.","authors":"Jianing Yang, Li Li, Yanan Xu, Yuguang Guan, Xiaoli Li","doi":"10.1186/s12993-025-00294-x","DOIUrl":"https://doi.org/10.1186/s12993-025-00294-x","url":null,"abstract":"<p><p>The TWIK-related K<sup>+</sup> channel (TREK-1), a member of the two-pore domain potassium(K2P) family, is characterized as a \"leaky potassium channel\" and is integral to the maintenance of the resting membrane potential. As the most abundant cell type in the central nervous system, astrocytes play important roles in the development of epilepsy by regulating the release of glutamate and the function of potassium channels. Previous studies have revealed that TREK-1 is involved in a range of neurological diseases, including epilepsy. In astrocytes, TREK-1 acts as a crucial regulator of the rapid release of glutamate and passive conductance. However, controversy remains about the expression levels of TREK-1-binding receptors in the process of the release and recycling of glutamate in tripartite synapses. Thus, elucidating the pathological mechanisms involving TREK-1 in epilepsy could significantly increase our understanding of the pathophysiological basis of diseases and facilitate the identification of potential targets for novel therapeutic interventions. Here, we review the physiological function of TREK-1 and studies examining the role of TREK-1 in epilepsy, with a particular emphasis on its interactions with glutamate at tripartite synapses. Furthermore, we provide an analysis of the associated molecular mechanisms of this channel and conclude with an outlook on impending studies on TREK-1 as a novel therapeutic target for epilepsy.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"27"},"PeriodicalIF":3.3,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Victor Altmayer, Marcela Ovando-Tellez, Théophile Bieth, Bénédicte Batrancourt, Armelle Rametti-Lacroux, Lucy Bernardaud, Sarah Moreno-Rodriguez, Lucie Vigreux, Vincent Ledu, Béatrice Garcin, Raffaella Migliaccio, Isabelle Le Ber, Alizée Lopez-Persem, Richard Levy, Emmanuelle Volle
{"title":"Behavioral variant frontotemporal dementia as a model for understanding the cognitive and cerebral determinants of verbal creativity.","authors":"Victor Altmayer, Marcela Ovando-Tellez, Théophile Bieth, Bénédicte Batrancourt, Armelle Rametti-Lacroux, Lucy Bernardaud, Sarah Moreno-Rodriguez, Lucie Vigreux, Vincent Ledu, Béatrice Garcin, Raffaella Migliaccio, Isabelle Le Ber, Alizée Lopez-Persem, Richard Levy, Emmanuelle Volle","doi":"10.1186/s12993-025-00292-z","DOIUrl":"https://doi.org/10.1186/s12993-025-00292-z","url":null,"abstract":"<p><strong>Background: </strong>Although creativity is an essential cognitive function to adapt to an ever-changing world, its neurocognitive and cerebral bases still need clarification. Current models highlight the interaction between associative and executive processes underpinned by the default mode (DMN), executive control (ECN) and salience networks (SN). Furthermore, recent neuroimaging studies highlight the key role of the prefrontal cortex (PFC), located at the crossroads of these networks. Hence, behavioral variant frontotemporal dementia (bvFTD), characterized by progressive neurodegeneration principally impacting the prefrontal cortex and the intrinsic connectivity of these three creativity-related networks, represents a unique model to study creativity. In this study involving 14 bvFTD patients and 20 matched controls, we used a simple word-to-word association task (FGAT) to explore the specific cognitive processes involved in remote thinking, i.e., the production of creative semantic associations. Using voxel-based morphometry, we uncovered critical brain regions for each component and then characterized these regions' intrinsic connectivity profiles using resting-state functional connectivity in healthy controls.</p><p><strong>Results: </strong>We dissociated four key cognitive components underlying remote thinking: spontaneous associative thinking, inhibition of unoriginal responses, intentional remote associative thinking, and verbal initiation; and replicated them in three independent datasets. Spontaneous associative thinking relied on temporal and cerebellar regions involved in low-order and automatic semantic processing, connected with the DMN, ECN and SN. Inhibition of prepotent unoriginal responses depended on key nodes of the SN. The ability to intentionally generate remote semantic associations was underpinned by key regions of the DMN. Finally, initiation of verbal responses relied on the right dorsolateral PFC, connected to the ECN. BvFTD patients were impaired in the last three components. Two components, cognitive inhibition and intentional remote thinking, mediated the link between atrophy in critical regions and an independent measure of creative abilities.</p><p><strong>Conclusions: </strong>These findings advance our understanding of creative neurocognition, distinguishing components of creative thinking and clarifying their critical cerebral bases, and participate in the characterization of creativity impairment in patients with bvFTD.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"26"},"PeriodicalIF":3.3,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"C18:0 GM3 ganglioside's efficacy in LPS-induced parkinsonism: neuroprotection, inflammatory inhibition and gliosis mitigation.","authors":"Tsung-Ta Liu, Cheng-Tsung Liu, I-Hsun Li, Yu-Chieh Chu, Hao-Yuan Hung, Chuang-Hsin Chiu, Ta-Kai Chou, Shiao-Yun Li, Tin-An Wang, Jui-Hu Shih","doi":"10.1186/s12993-025-00289-8","DOIUrl":"10.1186/s12993-025-00289-8","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is an incurable neurological disorder, and current pharmacological therapies primarily address symptoms without halting disease progression. Emerging evidence highlights PD as a neuroinflammatory disease, with chronic brain inflammation preceding the onset of motor dysfunction. This study investigates the role of C18:0 GM3, a long-chain fatty acids-containing ganglioside, in modulating inflammatory responses in PD, exploring its therapeutic potential in mitigating LPS-induced parkinsonism.</p><p><strong>Methods: </strong>Male C57BL/6 mice were utilized in an LPS-induced PD model to evaluate the neuroprotective effects of C18:0 GM3 ganglioside. Pre-treatment with C18:0 GM3 was assessed through behavioral tests, including rotarod and beam-walking, to determine motor function improvements. Dopaminergic neurotoxicity was quantified using [<sup>18</sup>F]FE-PE2I positron emission tomography (PET) imaging and tyrosine hydroxylase (TH) staining. The anti-inflammatory and anti-gliosis effects of C18:0 GM3 were analyzed by measuring cytokine levels (IL-1β, TNF-α) and by assessing Iba1 and GFAP immunoreactivity as indicators of microglial and astrocytic changes, respectively.</p><p><strong>Results: </strong>Pre-treatment with C18:0 GM3 ganglioside significantly enhanced motor coordination and balance, as evidenced by improved performance in rotarod and beam-walking tests. Furthermore, C18:0 GM3 ganglioside effectively attenuated LPS-induced dopaminergic neurotoxicity, evidenced by increased striatal dopamine transporter availability on [<sup>18</sup>F]FE-PE2I PET imaging and the preservation of TH-positive neurons in the striatum. In addition, C18:0 GM3 markedly suppressed the expression of pro-inflammatory cytokines, including IL-1β and TNF-α, along with cyclooxygenase-2 levels. C18:0 GM3 also reduced gliosis, as demonstrated by a decrease in Iba1-positive microglial cells and GFAP-positive astrocytes.</p><p><strong>Conclusion: </strong>Our data indicate that C18:0 GM3 primarily attenuates the TLR4-driven inflammatory cascade initiated by intrastriatal LPS, thereby secondarily preserving striatal dopaminergic terminals and improving motor deficits. Although these results highlight anti-inflammatory neuroprotection, additional studies are required to determine whether GM3 also modulates downstream Parkinson-specific processes such as α-synuclein aggregation or progressive neurodegeneration.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"25"},"PeriodicalIF":3.3,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}