Neurochemistry international最新文献

{"title":"Clinically relevant infraorbital nerve deflation and chronic constriction injury models of trigeminal neuralgia display unifying mechanisms","authors":"Srilakshmi Satti ,&nbsp;Shwetali Ramteke ,&nbsp;Sowmya Chaganti ,&nbsp;Hara Prasad Padhy ,&nbsp;Gananadhamu Samanthula ,&nbsp;Manoj P. Dandekar","doi":"10.1016/j.neuint.2025.106052","DOIUrl":"10.1016/j.neuint.2025.106052","url":null,"abstract":"<div><h3>Background</h3><div>Trigeminal neuralgia is a debilitating pain condition that occurs due to the deflation of trigeminal nerve. Herein, we developed clinically relevant trigeminal neuralgia model using a distal infraorbital trigeminal nerve chronic deflation injury (dIoN CDI) in male and female rats. The results were compared with an existing distal infraorbital nerve chronic constriction injury (dIoN CCI) model.</div></div><div><h3>Methods</h3><div>Pain-related assessments were conducted by von-Frey filaments, orofacial-pain assessment device (OPAD), grooming time and rat-grimace scale (RGS). Anxiodepressive-phenotypes were assessed by elevated-plus maze test (EPM), sucrose-preference test (SPT), forced-swim test (FST), splash test. Brain, trigeminal nerve, faeces and blood samples were collected for molecular analysis.</div></div><div><h3>Results</h3><div>Rats subjected to dIoN CCI and dIoN CDI surgery displayed a decrease in von-Frey threshold and lick number in OPAD. The grooming time and RGS also indicated development of pain. A significant decrease in sucrose consumption in male rats and less exploration of open arms in EPM test by female rats, indicated the development of chronic pain-generated anxiodepressive behaviors. In biomarkers analysis, dIoN CCI and dIoN CDI groups showed elevated expression of calcitonin gene-related peptide and substance P in spinal trigeminal nucleus and/or ganglia. These groups also showed enhanced levels of dopamine, acetylcholine, 5-HT, and corticosterone and decreased concentration of GABA and noradrenaline in frontal and somatosensory cortices, brainstem and plasma. We also noted altered levels of sex hormones, fecal short-chain fatty acids, and occludin expression in the colon.</div></div><div><h3>Conclusion</h3><div>These results indicate that both trigeminal neuralgia models display unifying principles in male and female rats.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106052"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro pharmacological activity of twenty-eight synthetic cannabinoid receptor agonists at the type 1 and 2 cannabinoid receptors","authors":"Gabrielle Mercier ,&nbsp;Kawthar A. Mohamed ,&nbsp;Ayat Zagzoog ,&nbsp;Laura Cropper ,&nbsp;Brendan Ritchie ,&nbsp;Zhiyun Jin ,&nbsp;Mikin Patel ,&nbsp;Robert B. Laprairie","doi":"10.1016/j.neuint.2025.106039","DOIUrl":"10.1016/j.neuint.2025.106039","url":null,"abstract":"<div><div>Synthetic cannabinoid receptor agonists (SCRAs) are a class of novel psychoactive substances whose prevalence in illegal markets continues to grow. Δ⁹-tetrahydrocannabinol (THC) is the primary intoxicating compound present in cannabis and is well-known to behave as a partial agonist at both the type 1 and 2 cannabinoid receptors (CB1R, CB2R). Unlike THC, the SCRAs characterized to date generally behave as CB1R and/or CB2R full agonists. The high potency and full agonism of these ligands are thought to drive the toxicity of SCRAs, including psychoses, emesis, and tachycardia. In this study, twenty-eight compounds (including the reference ligands CP55,940 and THC) were evaluated for binding affinity, Gi protein-dependent inhibition of cAMP, and βarrestin2 recruitment in Chinese hamster ovary (CHO–K1) cells stably expressing either receptor. Radioligand binding results demonstrate a general lack of selectivity between cannabinoid receptor subtypes. In signaling assays, most compounds displayed the anticipated full agonism with low nanomolar potency characteristic of SCRAs. Many compounds displayed bias for the inhibition of cAMP over the recruitment of βarrestin2, and this was especially true at CB2R, where several compounds were inactive in the βarrestin2 recruitment assay. However, no clear structure-activity relationship emerged among the tested SCRAs that could account for their selectivity, potency, efficacy, or bias, although potential patterns are discussed herein. Overall, our data support growing evidence that the cannabinoid receptors accommodate a diverse range of ligands, and that compound function may be dictated by factors that are not yet well characterized, such as binding kinetics.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106039"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics reveals changes in astrocyte fatty acid metabolism during early stages of Alzheimer's disease","authors":"Jie Zhong ,&nbsp;Manhui Li ,&nbsp;Ziwei Dai ,&nbsp;Jun Wan","doi":"10.1016/j.neuint.2025.106049","DOIUrl":"10.1016/j.neuint.2025.106049","url":null,"abstract":"<div><h3>Background</h3><div>Although astrocytes are known to contribute to Alzheimer's disease (AD) progression, their dynamic molecular alterations remain poorly characterized, particularly in early stages of the disease.</div></div><div><h3>Methods</h3><div>We performed multi-omics profiling (transcriptomics, proteomics, spatial metabolomics) of astrocytes from APP/PS1 and WT mice to characterize dynamic changes during AD progression. To assess similar changes in early human AD, we analyzed single-nucleus RNA sequencing data from human samples.</div></div><div><h3>Results</h3><div>Transcriptomic analysis of astrocytes from APP/PS1 and WT mice at five time points (2, 4, 6, 9, and 12 months of age) showed notable gene expression differences at 6 months, with reduced activity in fatty acid metabolism pathways (e.g., PPAR signaling, biosynthesis of unsaturated fatty acids). An astrocyte-specific metabolic model confirmed these disruptions. Proteomic analysis corroborated this by showing decreased activity in pathways like butanoate metabolism and PPAR signaling. Spatial metabolomics of brain slices from APP/PS1 and WT mice highlighted fatty acid enrichment in the hippocampus and cortex, alongside differential metabolites specific to the AD mouse model. Single-cell RNA sequencing analysis of human brain samples further showed fatty acid metabolism abnormalities in astrocytes from early AD cases versus controls, emphasizing its role in AD progression.</div></div><div><h3>Conclusion</h3><div>Our study identified abnormal fatty acid metabolism as an early feature of astrocytes in AD, suggesting an association between dysregulated fatty acid metabolism and disease progression.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106049"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting ferroptosis by electroacupuncture offers a therapeutic regimen for brain injury after ischemic stroke","authors":"Wenjing Li,&nbsp;Qiang Li","doi":"10.1016/j.neuint.2025.106038","DOIUrl":"10.1016/j.neuint.2025.106038","url":null,"abstract":"<div><div>Ischemic stroke (IS), the most prevalent form of stroke, remains a significant healthcare challenge and imposes a considerable burden on affected individuals. Ferroptosis, a form of regulated cell death (RCD) characterized by iron overload -induced lipid peroxidation, was identified as a contributor to induce cell death following brain injury after ischemic stroke. Targeting ferroptosis is a novel therapy regimen for IS. And seeking novel therapy is unmet need for IS. Electroacupuncture (EA) has been revealed to have neuroprotective effect against IS and recommended to treat IS by World Health Organization (WHO) for years, but the specific mechanism underlying EA-mediated neuroprotection is still elusive. Emerging evidences have shown that EA alleviates brain injury after ischemic stroke by inhibiting ferroptosis; however, the mechanism by which EA suppresses ferroptosis against IS has not been sufficiently clarified. In this review, we first summarizes the core molecular mechanism of ferroptosis, with an focus on interpret how ferroptosis leads to the genesis of brain injury after ischemic stroke and the novel regulation of ferroptosis during the brain injury after ischemic stroke. We then highlights our emphasize on the emerging evidences that have revealed EA inhibit ferroptosis and review their pharmacological mechanisms against brain injury after ischemic stroke. This review highlights EA as a novel therapeutic regimen for ischemic stroke by suppressing ferroptosis, synthesizing mechanistic insights into iron-dependent lipid peroxidation pathways, evaluating emerging experimental evidence of EA's neuroprotection, and proposing targeted clinical strategies to mitigate post-stroke brain injury.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106038"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144896185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Further characterisation of the intrastriatal 6-OHDA Parkinson's disease model with non-motor symptom replication and widespread catecholamine dysfunction in male mice","authors":"Alisha Braun ,&nbsp;Jessica Racz ,&nbsp;Sanjay Garg ,&nbsp;Larisa Bobrovskaya","doi":"10.1016/j.neuint.2025.106054","DOIUrl":"10.1016/j.neuint.2025.106054","url":null,"abstract":"<div><div>The 6-OHDA mouse model of Parkinson's disease is not well characterised, with variable dosages, injection sites and timeframes. This study further characterised the unilateral intrastriatal 8 μg 6-OHDA mouse model using a four-week protocol, with replication of motor and some non-motor symptoms in male mice. Non-motor symptom replication included cognitive impairment and gastrointestinal dysfunction. Olfactory dysfunction and anxiety-like behaviour were unable to be replicated in this study. Parkinson's disease pathology, particularly non-motor pathology, was also investigated in this study which found the intrastriatal 6-OHDA lesion caused widespread catecholamine dysfunction outside of the nigrostriatal pathway, including the mesocortical and mesolimbic pathway. Proteins involved in neuroinflammation (GFAP), oxidative stress defence (SOD2) and synaptic proteins (SNAP25) were altered, as seen in Parkinson's disease pathology, in the brains of the 6-OHDA lesioned mice.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106054"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPP1 expression after spinal cord compression injury and its effects on glial cell activation","authors":"Linkai Lei ,&nbsp;Xinping Wang ,&nbsp;Jijuan Zhao","doi":"10.1016/j.neuint.2025.106063","DOIUrl":"10.1016/j.neuint.2025.106063","url":null,"abstract":"<div><h3>Purpose</h3><div>To study the role and mechanism of SPP1 in spinal cord injury.</div></div><div><h3>Methods</h3><div>We created a rat model of spinal cord compression injury (SCI) and examined the expression of SPP1 in spinal cord tissue using western blotting and immunofluorescence staining. We assessed motor function and pathological repair in SCI rats using the BBB locomotor scale, swimming tests, HE staining, Nissl staining, myelin staining, immunofluorescence, and western blot experiments. Additionally, we examined microglial activation and inflammatory phenotypes to analyze underlying mechanisms. To determine if SPP1's effects are linked to MK2, we used the MK2 inhibitor PF-364402.</div></div><div><h3>Results</h3><div>After spinal cord injury, the expression level of SPP1 exhibited a significant increase, peaking on the third day post-injury. A co-localization relationship was noted with Iba-1-labeled microglia. Reduced SPP1 expression enhanced motor function recovery and aided in spinal cord tissue repair after injury in mice. Low SPP1 expression modulated glial cell inflammation, reducing the iNOS-labeled pro-inflammatory phenotype and increasing the Arg-1-labeled anti-inflammatory phenotype. This modulation subsequently inhibited the activation of microglia. Furthermore, we validated the inhibitory effect of low SPP1 expression on the activation of the MK2 signaling pathway, which was associated with a reduction in the phosphorylation levels of MK2, p38, and NF-κB.</div></div><div><h3>Conclusion</h3><div>This study found that SPP1 was highly expressed in rats with spinal cord injury and was associated with microglial activation and inflammatory phenotype transformation. Low levels of SPP1 promoted neural repair and motor function recovery, which may be related to the MK2 pathway.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106063"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential of mulberry (Morus alba L.) leaf extract against pro-aggregant tau-mediated inflammation and mitochondrial dysfunction","authors":"Te-Hsien Lin ,&nbsp;Pei-Hsuan Tseng ,&nbsp;I-Cheng Chen ,&nbsp;Chung-Yin Lin ,&nbsp;Ming-Chung Lee ,&nbsp;Kuo-Hsuan Chang ,&nbsp;Guey-Jen Lee-Chen ,&nbsp;Chiung-Mei Chen","doi":"10.1016/j.neuint.2025.106042","DOIUrl":"10.1016/j.neuint.2025.106042","url":null,"abstract":"<div><div>In Alzheimer's disease (AD), Tau aggregates trigger microglial activation to release inflammatory factors and cause mitochondrial dysfunction, oxidative stress, and neuronal damage. With abundant potent antioxidants, mulberry (<em>Morus alba</em> L.) leaf extract has the potential to treat diseases associated with neuroinflammation, mitochondrial dysfunction, and oxidative stress. This study examined the neuroprotective effects of a mulberry leaf extract against pro-aggregant Tau-mediated inflammation and mitochondrial dysfunction in SH-SY5Y cells expressing the ΔK280 Tau repeat domain (Tau_RD). His-tagged ΔK280 Tau_RD fibrils prepared from <em>E. coli</em> activated BV-2 microglia, as revealed by their altered morphology, increased nitric oxide production, and elevated ionized calcium binding adaptor molecule 1 (IBA1) and major histocompatibility complex 2 (MHCII) expression. The mulberry leaf extract suppressed the production of pro-inflammatory mediators, including NO, IL-1β, IL-6, and TNF-α, and the expression of NLR family pyrin domain-containing 3 (NLRP3) and caspase-1 (CASP1) in ΔK280 Tau_RD fibril-stimulated BV-2 cells. Application of conditioned media collected from ΔK280 Tau_RD fibril-activated BV-2 cells induced cellular inflammation in ΔK280 Tau_RD-DsRed-expressing SH-SY5Y cells. The mulberry leaf extract protected these cells by suppressing lactate dehydrogenase (LDH) release, caspase-3 activity, NLR family pyrin domain-containing 1 (NLRP1), CASP1, IL-1β, IL-6, TNF-α, and reactive oxygen species as well as by enhancing neurite outgrowth. In addition, mulberry leaf extract increased mitochondrial membrane potential, lowered mitochondrial superoxide levels, and increased superoxide dismutase 2 (SOD2), NAD(P)H quinone dehydrogenase 1 (NQO1), glutamate-cysteine ligase catalytic subunit (GCLC), and nuclear factor erythroid 2-related factor 2 (NRF2) levels in SH-SY5Y cells. In conclusion, mulberry leaf extract displayed neuroprotective effects by exerting anti-inflammatory and antioxidative activities to ameliorate pathological Tau-mediated mitochondrial dysfunction in a human Tau cell model. The results of this study support the notion that the mulberry leaf extract is a potential disease-modifying therapeutic agent for <span>AD</span>.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106042"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional effects of heavy metal exposures on N6-methyladenosine (m6A) methylation and other Epitranscriptomic modifications in the central nervous system","authors":"Niraj Lodhi ,&nbsp;Lauren Powell ,&nbsp;Jay S. Schneider","doi":"10.1016/j.neuint.2025.106064","DOIUrl":"10.1016/j.neuint.2025.106064","url":null,"abstract":"<div><div>Among different RNA methylations, N6-methyladenosine (m6A) is the most abundant in the brain and determines the fate of RNA through reversible processes using methyltransferases, demethylases, and methyl-binding proteins. The reversibility of m6A is an emerging regulatory mechanism for gene expression, regulating many aspects of RNA metabolism and influencing learning and memory processes. Global m6A profiles are dynamically modified via the activity of various writers, readers, and erasers. However, m6A alterations from exposure to heavy metals, including the metals lead (Pb), cadmium (Cd), cobalt (Co), and manganese (Mn) and the metalloid arsenic (As), and the impact on brain function, are not fully understood. This paper reviews recent work that may begin to shed light on how heavy metal exposures may affect m6A methylation and how this might impact central nervous system functioning.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106064"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of the β2-adrenoceptor by formoterol induces calcium-dependent exocytosis of synaptic vesicles at the neuromuscular junction in a sex-specific manner","authors":"Kivia B.S. Santos ,&nbsp;Matheus de Castro Fonseca ,&nbsp;Gabriel H.M. Teixeira ,&nbsp;Bruno Sanches ,&nbsp;Silvia Guatimosim ,&nbsp;Leonardo Rossi ,&nbsp;Pablo W. Verly ,&nbsp;Elisa Santiago Pereira ,&nbsp;Walter Cavalcante ,&nbsp;Alexander Birbrair ,&nbsp;Enrrico Bloise ,&nbsp;Juan C. Tapia ,&nbsp;Cristina Guatimosim","doi":"10.1016/j.neuint.2025.106040","DOIUrl":"10.1016/j.neuint.2025.106040","url":null,"abstract":"<div><div>Increasing evidence suggests that the sympathetic nervous system profoundly interacts with skeletal muscle, influencing both muscle fiber function and composition. β₂-ARs, the predominant adrenergic receptor subtype in muscle fibers, have been shown to enhance protein synthesis, reduce protein degradation, facilitate muscle contraction and relaxation, and improve neuromuscular junction (NMJ) transmission upon activation. In this study, we investigated the effects of Formoterol, a highly selective β₂-adrenoceptors (β₂-AR) agonist, on the presynaptic terminal of motor neurons. We used myography, FM1-43 fluorescent dye assays, and transmission electron microscopy (TEM) to evaluate the NMJ following β₂-AR activation. We demonstrated that β₂-AR activation by Formoterol enhances muscle contractility and both spontaneous and evoked exocytosis of acetylcholine (ACh)-containing synaptic vesicles at the mouse diaphragm NMJ. Formoterol-induced morphological changes in diaphragmatic NMJs were consistent with increased exo-endocytic activity. Notably, Formoterol-evoked exocytosis displayed sexual dimorphism, with females showing a significantly milder response compared to males. In females, Formoterol-induced synaptic vesicles exocytosis was mediated solely by P/Q-type voltage-activated Ca²⁺ channels, whereas in males, it involved both P/Q-type channels, transient receptor potential channel of the vanilloid subtype (TRPV) 1 calcium channels, and an additional, yet unidentified, component. Orchiectomized males exhibited responses to Formoterol similar to the females, whereas ovariectomy did not modify female drug responses, indicating that male hormonal environment orchestrates the sex-differences herein described. These findings not only highlight the importance of sex-specific mechanisms but also reveal a novel effect of β₂-AR activation directly on presynaptic terminals by Formoterol, enhancing exocytosis at the NMJ and thereby increasing neuromuscular transmission.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106040"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Constant light exposure promotes pathogenic tau hyperphosphorylation and phenotypic manifestations in Drosophila disease models","authors":"Prerna Aggarwal ,&nbsp;Virender ,&nbsp;Surajit Sarkar","doi":"10.1016/j.neuint.2025.106060","DOIUrl":"10.1016/j.neuint.2025.106060","url":null,"abstract":"<div><div>Chronic sleep disruption caused by constant artificial light exposure has emerged as both a comorbidity and a precursor of several neurodegenerative disorders, including tauopathies. Tauopathies, a group of neurodegenerative disorders, are characterised by the toxic accumulation of hyperphosphorylated tau in brain neurons. While disturbance in the sleep/wake cycle is an inherent clinical feature of tauopathies, the impact of prolonged light exposure on disease progression and severity has been inadequately investigated. We utilized <em>Drosophila</em> models of human tauopathies to examine the impact of uninterrupted exposure to light on tau-induced phenotypic markers during pathogenesis over a short period of aging. We observed that constant light exposure causes an earlier onset and increased severity of disease-associated phenotypes in an age-dependent manner. We further noted that these aggravated phenotypes are associated with increased pathogenic hyperphosphorylation of tau, leading to the rapid accumulation of relatively larger neurotoxic aggregates in neuronal cells and their subsequent degeneration. Overall, our study demonstrates that unhealthy light exposure accelerates the early onset and severity of tauopathy-related phenotypes, highlighting its potential relevance in developing management strategies for these devastating neurodegenerative disorders.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106060"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}