Molecular Neurobiology最新文献

{"title":"Activation of the C3 Complement Pathway in the Hippocampus Produces Anxiodepressive Effects in a Mouse Model of Inflammation Pain.","authors":"Aomei Zhang, Xinxin Zhang, Xiaohan Tang, Ming Liu, Jialing Xie, Suyun Li, Wenyu Cao, Huamao Zhou, Yang Xu","doi":"10.1007/s12035-025-05187-8","DOIUrl":"https://doi.org/10.1007/s12035-025-05187-8","url":null,"abstract":"<p><p>The comorbidity of anxiety and depression frequently occurs in patients with inflammatory pain, which requires further investigation. Previous evidence supports a close link between Complement Component 3 (C3) and affective disorders; however, whether C3 is involved in inflammatory pain-induced anxiodepression remains unclear. Using a mouse inflammatory pain model with Complete Freund's Adjuvant (CFA), we observed that the animals exhibited significant anxiodepression-like behaviors and that the expression of hippocampal C3 was obviously increased three weeks after CFA injection. Microinjection of the AAV vector that downregulates C3 into the hippocampus alleviated anxiodepression-like behaviors. Moreover, we noted that knocking down hippocampal C3 partially alleviated pain behavior in CFA-treated mice. Mechanistically, we found that the benefit of knocking down the hippocampal C3 may be due to inhibition of its downstream C3aR-GSK3β signaling pathway and restoration of glia activation and inflammatory response to levels similar to those found under non-inflammatory conditions. Consequently, our work reveals the critical role of the hippocampal C3/C3aR-GSK3β signaling pathway in inflammatory pain-induced anxiodepression-like behaviors, suggesting that C3/C3aR-GSK3β signaling is a potential therapeutic target for inflammatory pain-induced mental health conditions.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overexpression of mGlu_7B in Mice: Implications for Neurodevelopmental Disorders.","authors":"Geanne A Freitas, Kelly Weiss, Vaishnavi Bavadekar, Sheryl Anne D Vermudez, Nicole M Fisher, Aditi Buch, Shalini Dogra, Zixiu Xiang, Rocco G Gogliotti, Colleen M Niswender","doi":"10.1007/s12035-025-05183-y","DOIUrl":"https://doi.org/10.1007/s12035-025-05183-y","url":null,"abstract":"<p><p>Metabotropic glutamate receptor 7 (mGlu₇) is a G protein-coupled receptor (GPCR) involved in neurotransmitter release throughout the central nervous system (CNS). Low levels of the receptor are correlated with intellectual disability, autism, repetitive behaviors, and seizures in patients with neurodevelopmental disorders (NDDs), including the disease Rett syndrome. These findings suggest that increasing mGlu₇ activity may be of therapeutic benefit. In the current manuscript, we report the characterization of a novel transgenic mouse that overexpresses the human GRM7B splice variant at approximately fivefold higher levels compared to wild-type (WT) littermates. These animals exhibit a reciprocal decrease in expression of the mouse mGlu_7A splice isoform, suggesting feedback regulation of receptor expression. Previous studies from our lab and others have shown that mGlu₇ activation is permissive for long-term potentiation induction in the hippocampus and amygdala. Here, we identified subtle differences in agonist-modulated hippocampal field recordings in mice overexpressing mGlu_7B, but no changes in theta burst-induced long-term potentiation. Our lab previously characterized behavioral phenotypes in Grm7^-/- animals that were observed in other animal models of NDDs. Surprisingly, we find here that mGlu_7B-overexpressing mice exhibit similar phenotypes to previously reported studies in Grm7^-/- animals in repetitive behavior and cognition assays. Overall, these findings suggest that precise control of mGlu₇ may be required to avoid abnormal phenotypes.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Crosstalk Between Sepsis-Associated Encephalopathy and Alzheimer's Disease: Identifying Potential Biomarkers and Therapeutic Targets for Cognition.","authors":"Zhitong Wang, Zhiling Zhang, Jing Shi, Rongsheng Zhao","doi":"10.1007/s12035-025-05192-x","DOIUrl":"https://doi.org/10.1007/s12035-025-05192-x","url":null,"abstract":"<p><p>Patients with sepsis are at a heightened risk of long-term cognitive impairment, including neurodegenerative diseases; however, the underlying pathophysiological mechanisms remain incompletely understood. This study examines key genes associated with sepsis and Alzheimer's disease (AD), as well as their potential molecular mechanisms. We downloaded the GSE135838 dataset from the Gene Expression Omnibus (GEO) database and performed comparative analysis of differentially expressed genes (DEGs) using the AlzData database to identify co-expressed DEGs. Functional and protein-protein interaction (PPI) network analyses were used to identify hub genes and their associated molecular mechanisms. Animal experiments were conducted to validate the role of the central gene C5aR1 in the pathological processes of sepsis-related cognitive impairment, blood-brain barrier (BBB) disruption, and microglial activation. Co-culture experiments were performed to assess the protective effect of C5aR1 against inflammation-induced neuronal damage. In GSE135838, 25 DEGs exhibited consistent expression changes in the brain tissue of AD patients. Notably, LYZ, C5AR1, ZFP36, MPZL2, APOL4, CD163, SERPINA3, and CCL2 showed significant differential expression in the cortex and hippocampus of AD patients. KEGG pathway enrichment analysis revealed that among the 14 pathways meeting the criteria, the TNF signaling pathway demonstrated the highest significance. Key intersections of multiple GO enrichment terms included IL-6, ICAM1, CLEC4E, and PCK1. The top ten hub genes identified from the PPI network analysis included IL6, CCL2, ICAM1, CXCL1, CD163, C5AR1, SOCS3, CLEC4E, HSPB1, and HSPA1A. Pharmacological inhibition of the hub gene product C5aR1 using PMX205 improved cognitive and emotional dysfunction in CLP-induced septic mice and reduced BBB damage and microglial activation. Inhibition of C5aR1 also alleviated microglia-induced neuronal injury. In summary, the neuroimmune dysregulation caused by sepsis is correlated with potential pathological mechanisms in AD. This study provides additional molecular evidence for potential biomarkers and therapeutic targets for drug intervention in the risk of AD among sepsis survivors.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EP300 Regulates CD8br AC (TBNK Panel) to Facilitate Insomnia.","authors":"Xin Men, Qian Wang","doi":"10.1007/s12035-025-05188-7","DOIUrl":"https://doi.org/10.1007/s12035-025-05188-7","url":null,"abstract":"<p><p>Insomnia is a prevalent clinical condition that is caused by the interaction of environmental, inflammatory, immune system, physiological, and psychological factors. Nevertheless, the significance of lactylation-related gene in the pathogenesis of insomnia remains unknown. The causal relationship between lactylation-related gene and insomnia was initially analyzed using Mendelian randomization. Exposure was determined using cis-expression quantitative trait loci (cis-eQTL) from the Expression Quantitative Trait Locus Gen (eQTLGen) consortium. We obtained insomnia from the FinnGen database, which comprises 490,763 controls and 6776 cases. Subsequently, we performed a difference analysis of the Gene Expression Omnibus (Geo) data on insomnia and a summary-data-based MR (SMR) analysis to further validate our findings. We used a mediation approach by immune cells to study the effect of lactylation-related genes on insomnia. We identified one lactylation-related gene associated with insomnia. EP300 also passed the SMR test (p < 0.05), and heterogeneity was assessed using the auxiliary heterogeneity in dependent instruments (HEIDI) test (p > 0.05). Using data from the Geo database, the overall difference in EP300 expression between insomnia patients and healthy individuals was compared and found to be significant. A mediation analysis was employed to investigate the impact of immune cells and EP300 on insomnia. We found that EP300 may promote insomnia by regulating the CD8br AC (TBNK panel). This provides new insights into the relationship between lactylation-related genes and insomnia and serves as a novel therapeutic target for future research.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosome-Mediated Delivery of Amyloid Beta Modulators: A Potential Therapeutic Strategy for Alzheimer's Disease.","authors":"Tehreem Mushtaq, Huma Hameed, Ana Cláudia Paiva-Santos, Urwa Tariq, Anam Hameed","doi":"10.1007/s12035-025-05189-6","DOIUrl":"https://doi.org/10.1007/s12035-025-05189-6","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of amyloid-beta (Aβ) plaques and tau protein abnormalities, disrupting synaptic function and causing progressive cognitive decline. However, significant efforts in research are still hampered by current treatments, which are limited by poor penetration of the BBB and non-specific effects. Recent developments in nanotechnology and drug delivery have found exosomes as innovative carriers targeting Aβ. They have identified a novel approach to treating the underlying pathology of AD. Exosomes are naturally occurring extracellular vesicles with several unique advantages. They are biocompatible, can cross the BBB, and can be engineered to deliver therapeutic agents with precision. These agents range from small interfering RNA (siRNA), peptides, or drugs designed to either inhibit Aβ aggregation, enhance its clearance, or regulate the genes involved in its production. Among these agents, neural-derived exosomes offer great promise as they naturally attract neuronal tissue and, therefore, increase the specificity of the treatment. In preclinical studies, such therapies have proven encouraging by demonstrating reduced Aβ accumulation, a decrease in neuroinflammation, and cognitive improvement in models of AD. However, translation into clinical application faces some challenges, such as development of scalable methods of exosome production, drug loading efficiency, stability, and safety upon administration. The present review takes an outlook toward the growing area of targeting Aβ pathology via exosomes with potential benefits, recent breakthroughs, and open challenges. Harnessed therapy from exosomes can create groundbreaking-therapies in treating AD that hope for millions to come out from this devastator disease.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ecdysterone and High-Intensity Interval Training Mitigate Alzheimer's Pathology in Rats: Impacts on Depression, Synaptic Plasticity, and Neuroinflammation.","authors":"Parsa Gholipour, Alireza Komaki, Hesam Parsa, Mahdi Ramezani","doi":"10.1007/s12035-025-05168-x","DOIUrl":"https://doi.org/10.1007/s12035-025-05168-x","url":null,"abstract":"<p><p>The study focuses on the role of neuroinflammation and impaired synaptic plasticity in the progression of Alzheimer's disease caused by amyloid-beta accumulation. It examines the potential therapeutic effects of Ecdysterone, known for its anti-inflammatory and antioxidant properties, and high-intensity interval training, which may also support brain health. The primary goal is to assess how Ecdy and HIIT, alone or combined, influence depressive-like behavior, synaptic function, inflammation, and Aβ buildup in a rat model of AD. Ten days after Aβ administration, treatments began with Ecdy (10 mg/kg/day, orally) and/or HIIT, continuing for 8 weeks. Rats were tested for depression-like behavior using the forced swim test. Brain synaptic plasticity was measured through long-term potentiation at the perforant path-dentate gyrus synapse by analyzing population spike amplitude and fEPSP slope. Congo red staining was used to identify Aβ plaques in the brain, and neuroinflammatory markers were quantified in both the hippocampus and cerebral cortex. Aβ injection led to depression, impaired synaptic plasticity, increased inflammation, and Aβ buildup in the brain. While Ecdy and HIIT individually offered some protection, their combination was significantly more effective in improving depression, restoring synaptic function, reducing inflammation, and decreasing Aβ accumulation in both the hippocampus and cerebral cortex (0.05 > P). This data provides evidence that HIIT, accompanied by Ecdy, improves Aβ-induced depression-like behavior, which may be partly related to the amelioration of synaptic dysfunction, a decrease in neuroinflammation, and suppression of Aβ plaque formation.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"17β-Trenbolone Increases the Release of Lipocalin 2 via the Brain-Liver Axis and Causes Alzheimer's Disease-Like Symptoms in CSDS-Induced Mice.","authors":"Xiang Zuo, Xiaochen Kuang, Yudi Zhao, Jingyi Tuo, Huijuan Bai, Qili Zhao, Xin Zhao, Xizeng Feng","doi":"10.1007/s12035-025-05186-9","DOIUrl":"https://doi.org/10.1007/s12035-025-05186-9","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to investigate the neurological and behavioural effects of exposure to the environmental endocrine disruptor 17β-trenbolone (17-TB) exposure in chronic social defeat stress (CSDS)-induced mice and elucidate the role of lipocalin 2 (LCN2) in linking peripheral inflammation to neurodegeneration.</p><p><strong>Methods and materials: </strong>Male BALB/c mice were subjected to the CSDS paradigm and treated with 17-TB (100 μg/kg) or vehicle control for 10 consecutive days. Behavioural assessments, including novel object recognition test, novel object location test and social interaction test, were conducted to evaluate cognitive memory and social behaviour. Western blotting, ELISA and immunofluorescence were used to analyse LCN2 expression and related inflammatory markers in the liver and brain.</p><p><strong>Results: </strong>The results showed that 17-TB exposure exacerbated the induction of serum TNF-α and IL-1β inflammation in CSDS-induced mice, leading to activation of the hepatic IL-6 inflammatory factor pathway. This enhanced the release of hepatic LCN2 and stimulated its expression in the medial prefrontal cortex (mPFC) via the peripheral circulation, which subsequently activated the dorsal motor vagal nucleus (DMX) through cholinergic neuron (ChAT⁺) hyperactivation and c-Fos⁺ upregulation. This neurovisceral circuit ultimately induces hippocampal and cortical amyloid-β (Aβ) deposition, leading to cognitive memory and social deficits, thereby inducing Alzheimer's disease (AD)-like pathological changes.</p><p><strong>Conclusion: </strong>This study highlights the critical role of the brain-liver axis in inducing LCN2 release and ultimately cognitive deficits similar to AD-like symptoms in a 17-TB-exposed CSDS-induced mouse model, highlighting the risk of environmental endocrine disruptors causing neurodegenerative diseases that require further investigations and safety assessments.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pinocembrin Alleviates Postoperative Cognitive Dysfunction in Aged Mice by Modulating miR-384-5p/FZD1 Axis to Activate the Wnt/β-Catenin Pathway.","authors":"Jie Li, Xue-Li Peng, Xin-Yu Cheng, Jun-Jun Yang, Cui Cui, Jian-Hui Liu","doi":"10.1007/s12035-025-05181-0","DOIUrl":"https://doi.org/10.1007/s12035-025-05181-0","url":null,"abstract":"<p><p>Postoperative cognitive dysfunction (POCD) is a clinically recognized complication of surgery that compromises long-term neurological outcomes, though its mechanistic basis remains poorly defined. The flavonoid Pinocembrin (5,7-dihydroxyflavanone) exhibits anti-inflammatory, antioxidant, and neuroprotective effects. However, the precise mechanisms underlying Pinocembrin's role in modulating the pathogenesis and progression of POCD remain incompletely elucidated. Cognitive function was evaluated using the Morris water maze (MWM) test and open field test (OFT). Protein and mRNA expression levels were quantified by Western blotting and qRT-PCR, respectively. Neuronal apoptosis in hippocampal tissue was assessed using TUNEL staining, while BV-2 microglial apoptosis was analyzed by flow cytometry. Microglial activation was visualized via immunofluorescence staining. Pro-inflammatory cytokine concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Pinocembrin significantly improved cognitive function in elderly POCD mice, without altering locomotor activity or anxiety-like behaviors. Notably, Pinocembrin reduced neuronal apoptosis and microglia-induced inflammation in elderly POCD mice. Mechanistically, Pinocembrin attenuated BV-2 microglial apoptosis and M1 polarization by downregulating miR-384-5p. MiR-384-5p directly targets FZD1. Strikingly, Pinocembrin rescued FZD1 expression by downregulating miR-384-5p, while FZD1 knockdown abolished Pinocembrin's effects on microglial M1 polarization and apoptosis. This cascade activated the Wnt/β-catenin pathway, ultimately ameliorating cognitive deficits in POCD mice. Pinocembrin ameliorates POCD in aged mice by activating Wnt/β-catenin signaling via the miR-384-5p/FZD1 regulatory axis.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trichloroethylene Exposure and Parkinson's Disease: Environmental Risk, Metabolic Pathways, and Mechanistic Insights.","authors":"Ruifang Liu, Furong Zhang, Jianwei Lou, Fuyong Song","doi":"10.1007/s12035-025-05172-1","DOIUrl":"https://doi.org/10.1007/s12035-025-05172-1","url":null,"abstract":"<p><p>Trichloroethylene (TCE) is a widely used industrial solvent noted for its environmental persistence and unique metabolic profile. In recent years, a growing body of epidemiological research and experimental models has implicated TCE exposure as a potential environmental risk factor in the development of Parkinson's disease (PD). TCE undergoes biotransformation primarily via cytochrome P450-mediated oxidation and glutathione conjugation. These pathways generate reactive metabolites capable of disrupting mitochondrial function, inducing oxidative stress, and activating neuroinflammatory cascades. These mechanisms are thought to contribute to the selective degeneration of dopaminergic neurons in the substantia nigra-a hallmark of PD. This review systematically evaluates the literature concerning the environmental distribution, metabolic fate, and exposure routes of TCE. It also synthesizes current evidence linking TCE-induced neurotoxicity to the pathogenesis of PD. Particular emphasis is placed on several key mechanistic insights, including α-synuclein aggregation, inhibition of mitochondrial complex I, and the roles of oxidative damage and neuroinflammation, offering a comprehensive perspective on the potential role of TCE in PD development. Moreover, the review addresses the methodological challenges associated with quantifying chronic low-level TCE exposure in human populations and underscores the need for long-term cohort studies to better assess the associated neurotoxic risks.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the Neurotoxic Burden of Micro- and Nanoplastics: From Multi-model Experimental Evidence to Therapeutic Innovation.","authors":"Smita Kumari, M Yasmin Begum, Chingakham Chinglenthoiba, Khadga Raj Aran, Siva Parsad Panda, Mosleh Mohammad Abomughaid, Sorabh Lakhanpal, D Avinash, Niraj Kumar Jha, Rohan Gupta","doi":"10.1007/s12035-025-05174-z","DOIUrl":"https://doi.org/10.1007/s12035-025-05174-z","url":null,"abstract":"<p><p>The widespread production of plastic in all daily appliances and its poor non-biodegradable characteristics along with toxic plasticizers pose significant risks to human health, leading to several life-threatening conditions, including neurological illnesses, cardiovascular diseases, and cancer. Microplastics (MPs) (101 nm-5 mm) and nanoplastics (NPs) (≤ 100 nm) infiltrate the human body via the respiratory system, digestive tract, and dermal absorption, resulting in the alteration of numerous biological and cellular processes, including apoptosis, endoplasmic reticulum stress, DNA damage, oxidative stress, and inflammation, among others. The bioaccumulation of MPs and NPs disrupts the gut-brain axis, resulting in memory impairment, synapse malfunction, and ultimately cognitive deficits. Therefore, it is crucial to comprehend the molecular mechanisms by which MPs and NPs disrupt cellular function to assess their hazards to human health. This review explores the formation, behavior, toxicity, pollution, and health effects of MPs and NPs, while highlighting research gaps to encourage further studies on their unique properties and biological interactions. This review further elucidates the detrimental impact of MPs and NPs on the development and progression of neurological illnesses, as well as management strategies to alleviate the toxic effects of exposure to these substances.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}