Journal of Neurochemistry最新文献

{"title":"Potential Role of Intermittent Fasting on Food Reward-Related Responses","authors":"Roberto Carlos Pérez-Kast,&nbsp;César Huerta-Canseco,&nbsp;Alberto Camacho-Morales","doi":"10.1111/jnc.70195","DOIUrl":"https://doi.org/10.1111/jnc.70195","url":null,"abstract":"<p>Intermittent fasting (IF) has emerged as a potential strategy to address the impact of the current obesogenic environment, where the abundance of ultra-processed and highly palatable foods deeply activates the mesocorticolimbic circuit, enhancing their rewarding properties. IF decreases cravings and preferences for unhealthy foods. Mechanistically, IF modulates homeostatic responses in the hypothalamus and also dopaminergic activity within the reward system. Additionally, IF is linked to reductions in neuroinflammation and increases in neurotrophic factors such as brain-derived neurotrophic factor (BDNF), which support brain plasticity during reward for palatable foods. Current evidence in humans has started to decode the role of IF protocols and assess their long-term impact on homeostatic and food reward related to metabolic health. This review article will contribute to defines how IF modulates molecular and cellular plasticity to influence eating behavior by reducing the reward value and setting homeostatic responses for food.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-Specific Long-Term Effects of Perinatal Limosilactobacillus reuteri on Social Cognition, Gene Expression, and Gut Microbiota","authors":"Tatiana Siegler Lathrop,&nbsp;Inés Martínez Sanchez,&nbsp;Ioannis S. Chronakis,&nbsp;Rochellys Diaz Heijtz","doi":"10.1111/jnc.70199","DOIUrl":"https://doi.org/10.1111/jnc.70199","url":null,"abstract":"<p>Recent research highlights the potential of early-life probiotic interventions to promote brain health later in life. In this study, we investigated the long-term effects of <i>Limosilactobacillus reuteri</i> (<i>L. reuteri</i>) supplementation during a critical perinatal window (gestational Day 6 to postnatal Day 7) on behavioral, molecular, and gut microbiota outcomes in adult male and female BALB/c mice. Perinatal <i>L. reuteri</i> supplementation led to significant and lasting improvements in sociability, social recognition, and gut microbiota composition in male offspring. These changes were accompanied by increased gene expression of the anti-inflammatory cytokine <i>Il10</i> in both the striatum and colon of male offspring. Notably, expression of the oxytocin receptor (<i>Oxtr</i>), a key regulator of social and anxiety-like behaviors, was significantly increased in both the prefrontal cortex and striatum in males and females. However, probiotic-exposed females exhibited a distinct behavioral profile, showing a trend toward reduced anxiety-like behavior but impaired social recognition. They also displayed increased gene expression of the peptidoglycan transporters <i>Slc46a2</i> and <i>Slc46a3</i> in the striatum, whereas only <i>Slc46a2</i> was elevated in males, suggesting a potential mechanistic pathway underlying the observed sex-dependent effects. These findings indicate that perinatal <i>L. reuteri</i> supplementation modulates the microbiota–gut–brain axis in a sex-specific manner, influencing behavior, neuroimmune signaling, and gut microbiota composition. Our results underscore the importance of accounting for sex differences when developing early-life microbiota-based interventions for neurodevelopmental disorders and long-term brain health.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70199","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dopaminergic Modulation of Short-Term Associative Memory in Caenorhabditis elegans","authors":"Anna McMillen,&nbsp;Caitlin Minervini,&nbsp;Renee Green,&nbsp;Michaela E. Johnson,&nbsp;Radwan Ansaar,&nbsp;Yee Lian Chew","doi":"10.1111/jnc.70200","DOIUrl":"https://doi.org/10.1111/jnc.70200","url":null,"abstract":"<p>Forgetting, the inability to retrieve previously encoded memories, is an active process involving neurotransmission, second messenger signalling and cytoskeletal modifications. Forgetting is thought to be essential to remove irrelevant memories and to increase the capacity to encode new memories. Therefore, identifying key regulators of active forgetting is crucial to advance our understanding of neuroplasticity. In this study, we utilised the compact and tractable <i>Caenorhabditis elegans</i> model to investigate the role of the neurotransmitter dopamine in forgetting. We conducted butanone associative learning assays based on an established protocol and used mutant strains deficient in dopamine synthesis (tyrosine hydroxylase CAT-2 and dopamine transporter DAT-1) and signalling (G protein-coupled receptors DOP-1, DOP-2 and DOP-3) to assess the impact on learning and memory retention. Learning was measured immediately post-training, and memory retention was evaluated every 0.5 h up to 2 h. Our results show that animals lacking dopamine display a modest enhancement in learning relative to wild-type, with the learned association persisting for at least 2 h after training. We also found that D2-like receptors DOP-2 and DOP-3 act together to modulate the forgetting process, with D1-like receptor DOP-1 functioning redundantly. Furthermore, re-expression of CAT-2 tyrosine hydroxylase in ADE and/or CEP neurons was unable to rescue the memory retention phenotype observed in <i>cat-2</i> mutants, suggesting that dopamine release from all dopaminergic neurons is required to modulate forgetting. These findings highlight the critical role of dopamine in forgetting, consistent with findings in <i>Drosophila</i>, and suggest potential relevance for understanding memory retention during healthy ageing and in conditions with dopamine imbalances such as Parkinson's disease.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70200","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebral Dopamine Neurotrophic Factor (CDNF) Acts as a Trophic Factor Promoting Neuritogenesis in the Dorsal Root Ganglia (DRG) Neurons Through Activation of the PI3K Signaling Pathway","authors":"Raphael de Siqueira Santos,&nbsp;Flávia Natale Borba,&nbsp;Dahienne Ferreira de Oliveira,&nbsp;Marcelo Felippe Santiago,&nbsp;Alexandre Martins do Nascimento,&nbsp;Deborah Schechtman,&nbsp;Debora Foguel","doi":"10.1111/jnc.70194","DOIUrl":"https://doi.org/10.1111/jnc.70194","url":null,"abstract":"<p>The cerebral dopamine neurotrophic factor (CDNF) is a neurotrophic factor extensively studied in the central nervous system because of its neuroprotective effects; however, its role in the peripheral nervous system (PNS) remains less explored. In this study, we used primary dorsal root ganglia (DRG) explants to investigate the neuritogenic potential of exogenous CDNF, as well as its neuroprotective activity under trophic factor deprivation. Our findings demonstrate that CDNF-mediated neuroprotection remains unaffected by the addition of a Trk (tropomyosin receptor kinase) inhibitor or anti-nerve growth factor (NGF) antibody, indicating that CDNF's neurotrophic activity is independent of TrkA signaling. Furthermore, CDNF binding to KDEL-receptor (KDEL-R) was essential for its protective effect, as the CDNF variant lacking the KDEL-R binding sequence (CDNF-ΔKTEL) displayed no significant neuroprotection. Additionally, the simultaneous administration of NGF and CDNF to DRG explants resulted in an additive enhancement of their trophic activities. Notably, both CDNF- and NGF-induced neurotrophic effects were PI3K-dependent, reinforcing the role of this signaling pathway in their mechanisms of action. Taken together, our findings highlight CDNF's crucial role in the PNS, ensuring that NGF-independent neurogenesis can occur. This suggests that CDNF could be further explored in conditions where NGF levels are low or where NGF signaling inhibition is desirable, such as in chronic pain management.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70194","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-17 Stimulates Sensory Neurons and Sensitises Colonic Afferents to Noxious Stimuli in a PI3K Dependent Manner in Male Mice","authors":"Luke W. Paine,&nbsp;James P. Higham,&nbsp;Katie H. Barker,&nbsp;Sofia Pavlou,&nbsp;Fraser Welsh,&nbsp;Ewan St. John Smith,&nbsp;David C. Bulmer","doi":"10.1111/jnc.70191","DOIUrl":"https://doi.org/10.1111/jnc.70191","url":null,"abstract":"<p>Managing visceral pain associated with gastrointestinal (GI) disease remains a significant challenge due to the gut-related side effects and contraindicated use of many commonly used painkillers in people with inflammatory bowel disease (IBD). Consequently, it is crucial to deepen our understanding of the mediators and mechanisms underlying inflammatory pain in people with IBD. To do this, we compared bulk RNA sequencing data from colonic biopsy samples from people with IBD with single-cell RNA sequencing data from colon-projecting dorsal root ganglion (DRG) neurons in mice to generate an interactome of putative pro-nociceptive cytokine signalling pathways. This in silico analysis revealed a 10-fold increase in <i>IL17A</i> expression in samples from people with ulcerative colitis (UC) alongside marked co-expression of <i>Il17ra</i> with <i>Trpv1</i> in colon-projecting DRG neurons in mice, highlighting a likely role for interleukin-17 (IL-17) in colonic nociceptor signalling in people with UC. In support of this, Ca²⁺ imaging studies demonstrated that IL-17 stimulates DRG sensory neurons co-sensitive to capsaicin in male and female mice, with a similar proportion responding in neuron-enriched cultures generated by magnetic-activated cell sorting, thus confirming that IL-17 directly activates DRG neurons. IL-17-evoked Ca²⁺ signals were attenuated by TRPV1 inhibition, consistent with nociceptor activation, and blocked by inhibition of phosphoinositide 3-kinase (PI3K) activity, consistent with the known role for PI3K as a downstream effector of IL-17 receptor signalling. In keeping with these observations, IL-17 enhanced colonic afferent responses to colorectal distension at noxious distension pressures in male mice, an effect also blocked by PI3K inhibition. Overall, these findings demonstrate a pro-nociceptive effect of IL-17 in the GI tract, thus highlighting the potential utility of IL-17-targeting therapies to reduce pain in people with UC.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ropinirole Functions Through a Dopamine Receptor D2-Independent Mechanism to Ameliorate Amyotrophic Lateral Sclerosis Phenotypes in TARDBP-Mutant iPSC-Derived Motor Neurons","authors":"Hirotsugu Asano,&nbsp;Tetsuya Kawaguchi,&nbsp;Chris Kato,&nbsp;Satoru Morimoto,&nbsp;Masato Yano,&nbsp;Maki Minaguchi,&nbsp;Daisuke Yasuda,&nbsp;Komei Fukushima,&nbsp;Hideyuki Okano","doi":"10.1111/jnc.70183","DOIUrl":"https://doi.org/10.1111/jnc.70183","url":null,"abstract":"<p>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron (MN) degeneration. Ropinirole hydrochloride (ROPI), a dopamine receptor D2 (DRD2) agonist, was identified through phenotypic screening of MNs derived from patient-derived induced pluripotent stem cells (iPSCs) as a disease model and has emerged as a promising candidate drug for ALS treatment. The ROPALS trial, a phase I/IIa trial in patients with ALS, suggested the safety and efficacy of ROPI, albeit in a small sample size. Interestingly, a DRD2 antagonist and modulator only partially mitigated the suppressive effect of ROPI on the ALS phenotype, and the detailed mechanism of ROPI activity remains unclear. Therefore, in this study, we investigated whether the therapeutic effects of ROPI in ALS are dependent on DRD2. For this purpose, we generated DRD2-deficient iPSCs and showed that ROPI effectively reduced neuronal cell death, reactive oxygen species (ROS) production, and neuronal hyperexcitation, independently of DRD2. Further analyses revealed that ROPI corrected aberrant RNA splicing and restored the mRNA expression of mitochondrial proteins in a DRD2-independent manner. Our findings suggest that ROPI not only functions as a canonical DRD2 agonist but also has pleiotropic DRD2-independent effects, offering a novel avenue for treatment strategies that target multiple pathways involved in ALS pathology.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations of NMDAR Subunits in the Cerebrospinal Fluid Across Neurodegenerative and Immunological Disorders","authors":"Sergio Escamilla,&nbsp;Rocío Pérez-González,&nbsp;Carmen Márquez-Marco,&nbsp;Elena Camporesi,&nbsp;Gunnar Brinkmalm,&nbsp;Alessandro Padovani,&nbsp;Andrea Pilotto,&nbsp;Chiara Tolassi,&nbsp;Davide Arici,&nbsp;Irene Volonghi,&nbsp;Henrik Zetterberg,&nbsp;Kaj Blennow,&nbsp;Jesús Pérez-Pérez,&nbsp;Jaime Kulisevsky,&nbsp;Inmaculada Cuchillo-Ibáñez,&nbsp;Javier Sáez-Valero","doi":"10.1111/jnc.70192","DOIUrl":"https://doi.org/10.1111/jnc.70192","url":null,"abstract":"<p>N-methyl-D-aspartate receptors (NMDARs) are glutamate-binding calcium channels that play a key role in brain function and have been linked to many neurological disorders. NMDARs are multi-pass membrane heterotetrameric complexes composed of two compulsory GluN1 subunits and two GluN2 (A-D) or GluN3 (A-B) subunits, from which GluN1, GluN2B, GluN2A, and GluN3A are widely expressed in the adult brain. This study assesses the presence of GluN1, GluN2B, GluN2A, and GluN3A in the cerebrospinal fluid (CSF) from healthy individuals, viral and autoimmune encephalitis, Huntington's disease (HD) and Alzheimer's disease (AD) patients. Samples were run in SDS-PAGE under reducing conditions and resolved with different anti-ectodomain and anti-C-terminal antibodies that combined with immunoprecipitation analyses, served to demonstrate the presence of full-length GluN1, GluN2A, GluN2B, and GluN3A in CSF. These NMDAR subunit complexes are not associated with extracellular vesicles. As a proof of concept of the identity of NMDAR subunits in the CSF, we demonstrated reduced levels of GluN1 in the CSF from patients with autoimmune encephalitis caused by anti-GluN1 antibodies compared with other causes of encephalitis; and showed a depletion of CSF GluN3A in a <i>Grin3a</i> knockout mouse model. Moreover, we observed higher GluN3A levels in CSF in both asymptomatic and symptomatic HD patients; while GluN2A levels were lower in CSF from AD patients. In conclusion, here we demonstrate the presence of NMDAR full-length subunits in CSF and that changes in NMDAR subunits balance could serve to identify alterations related to pathological conditions.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70192","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Neurotransmission to Retinal Pathophysiology: Unraveling the Role of GABA Receptors in Retinal Disease Progression","authors":"Alan E. Medina Arellano,&nbsp;Jesus Silvestre Albert-Garay,&nbsp;Nadia Flores Huerta,&nbsp;Karla Tovar Hernández,&nbsp;Matilde Ruiz-Cruz,&nbsp;Lenin Ochoa-de la Paz","doi":"10.1111/jnc.70198","DOIUrl":"https://doi.org/10.1111/jnc.70198","url":null,"abstract":"<p>Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system (CNS). The biological effects of GABA are mediated by activating its receptors, GABA_A or GABA_B, which are distributed across various tissues, predominantly in the brain and retina. The retina is a neural tissue responsible for receiving and transducing light stimuli. Within this tissue, GABA receptors (GABARs) primarily mediate lateral inhibition in the retina. In recent years, several studies have focused on elucidating the potential role of GABARs in retinal diseases, such as diabetic retinopathy (DR), retinitis pigmentosa (RP), glaucoma, and age-related macular degeneration (AMD). This review aims to present the most significant findings from recent years regarding the involvement of GABA receptors in retinal pathologies. Additionally, it highlights the potential of GABA receptors as targets for developing precise therapies or adjunctive strategies for treating retinal diseases.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70198","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contrasting Behavioural and Biochemical Characteristics of Normal and Spontaneously α-Synuclein-Deficient Mice Treated With MPTP","authors":"W. H. Powell,&nbsp;A. Ghita,&nbsp;F. C. Pascut,&nbsp;K. F. Webb,&nbsp;A. Newman-Tancredi,&nbsp;M. M. Iravani","doi":"10.1111/jnc.70201","DOIUrl":"https://doi.org/10.1111/jnc.70201","url":null,"abstract":"<p>α-Synuclein is the primary toxic constituent of Lewy bodies, but its exact function under homeostatic conditions remains elusive. To better understand the role of α-synuclein, we compared two C57BL sub-strains: the normal α-synuclein-expressing J6 and the α-synuclein-deficient J6-OlaHSD, for behavioural, dopaminergic and glial integrity in substantia nigra (SN) and caudate putamen (CPu) before and after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. After MPTP treatment, J6 mice showed significant weight loss (−7% by Day 10), whereas OlaHSD mice maintained stable body weight. At baseline, J6 mice exhibited 33% higher locomotor activity but 38% more thigmotaxis, and 33% less endurance on the Rotarod test than OlaHSD mice. Loss of tyrosine hydroxylase-positive neurons was similar in OlaHSD (−40%) and J6 mice (−34%). J6 mice had double the SN GFAP-ir cells of J6-OlaHSD, a difference that was unchanged by MPTP treatment. In the CPu, MPTP increased GFAP-ir cells in both strains, but Iba1-ir cells significantly increased only in MPTP-treated OlaHSD mice, compared to J6 strain. We further compared the biochemical signatures using Raman micro-spectroscopy. The Raman spectra of the freshly cut SN sections showed a greater shift in the α-helix to β-sheet protein conformation ratio in MPTP-induced J6 mice, likely due to the absence of the <i>Snca1</i> gene in OlaHSD mice. These findings suggest that the absence of α-synuclein plays a subtle role in the behavioural and neurochemical differences but has no significant effect on dopaminergic neurotransmission. It is therefore concluded that the presence of α-synuclein is important for non-dopaminergic behaviours such as anxiety-like behaviours and regulation of body weight. Under toxic challenge, gliosis in the SN and CPu may be regulated by α-synuclein. This study also emphasises the utility of Raman spectroscopy as a potential tool for identifying subtle protein conformation differences in mice with and without <i>Snca1</i>.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70201","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Common miRNAs, Genes, and Regulatory Pathways in Alzheimer's Disease and Type 2 Diabetes Mellitus: An Integrative Analysis of Systematic Reviews, Bioinformatics and Data Mining","authors":"Lívia Cristina Ribeiro Teixeira,&nbsp;Jessica Diniz Pereira,&nbsp;Izabela Mamede,&nbsp;Paulo Caramelli,&nbsp;Vítor Corrêa Silva,&nbsp;Adriano Alonso Veloso,&nbsp;Marcelo Rizzatti Luizon,&nbsp;Karina Braga Gomes","doi":"10.1111/jnc.70196","DOIUrl":"https://doi.org/10.1111/jnc.70196","url":null,"abstract":"<p>Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are frequent conditions affecting older adults, with evidence suggesting a higher predisposition for AD in diabetic patients. MicroRNAs (miRNAs) are proposed as regulators of gene expression in the mutual pathways among these diseases. This study aimed to investigate circulating miRNAs found to be expressed both in AD and T2DM, as well as their target genes and associated molecular pathways, using systematic reviews (SRs), bioinformatics analyses, and data mining. Two independent SRs were conducted to identify differentially expressed miRNAs in AD and T2DM compared to their respective controls. Searches covered major databases (EMBASE, PubMed, Cochrane, Scopus, Cinahl, Web of Science), gray literature, and reference lists, following the Joanna Briggs Institute (JBI) and PRISMA guidelines. Results were combined to identify miRNAs shared by both AD and T2DM, with target genes extracted from miRTarBase. Pathway enrichment analysis was performed using EnrichR, and relevant pathways were ranked based on gene involvement frequency with artificial intelligence tools. From the SRs (AD: 49 studies; T2DM: 104 studies), 21 miRNAs were identified as commonly expressed (10 upregulated, and 11 downregulated). 337 and 233 genes are potential targets for these down- and upregulated miRNAs, respectively. The key pathways identified from those genes were the TCR-RAS signaling cascade for downregulated miRNAs and the extracellular matrix pathway for upregulated miRNAs. Our findings highlight shared biological pathways between AD and T2DM and provide insights into their shared pathophysiology and potential therapeutic targets.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70196","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}