Brain Research最新文献

{"title":"Plumbagin as a potential therapeutic agent for scopolamine-induced Alzheimer’s disease: Mechanistic insights into GSK-3β inhibition","authors":"Rabiya Ahsan ,&nbsp;Mohd Muazzam Khan ,&nbsp;Anuradha Mishra ,&nbsp;Gazala Noor ,&nbsp;Usama Ahmad","doi":"10.1016/j.brainres.2025.149650","DOIUrl":"10.1016/j.brainres.2025.149650","url":null,"abstract":"<div><h3>Background</h3><div>The study aimed to evaluate Plumbagin’s neuroprotective potential against scopolamine-induced Alzheimer’s disease, proposing that its effects may involve GSK-3β inhibition, a key factor in tau hyperphosphorylation, to promote neuroprotection in Wistar rats.</div></div><div><h3>Methods</h3><div>Alzheimer’s was induced in male Wistar rats. After acclimatization, the rats were subjected to daily intraperitoneal treatment with scopolamine (0.7 mg/kg) and oral administration of Plumbagin (10 mg/kg) for 13 days. The cognitive function of treated rats was evaluated using the Morris water maze test, along with assessments of locomotor activity, acetylcholinesterase activity (AChE), protein levels, antioxidant parameters, cytokines and Brain-Derived Neurotrophic Factor (BDNF) and brain histopathology (hippocampus).</div></div><div><h3>Results</h3><div>The Plumbagin (10 mg/kg, oral) as given orally significantly improved neurobehavioral alterations compared to Alzheimer’s induced group. Scopolamine impaired cognitive function and increased locomotor activity (^#P &lt; 0.05). Treatments improved Morris water maze performance, reducing Escape latency time and increasing Time spent in the target quadrant (*P &lt; 0.05). Biochemically, treatments significantly improved BDNF (*P &lt; 0.05), decreased AChE activity, oxidative stress, reduced Interleukin-6 and Tumor Necrosis Factor Alpha (*P &lt; 0.05) and reversed Scopolamine induced hippocampal neuronal loss (^##P &lt; 0.01). Plumbagin showed significant (*P &lt; 0.05) neuroprotective effects, improving cognitive function, reducing AChE activity, Malondialdehyde, oxidative stress, and neuroinflammatory markers exceeding individual treatments in the scopolamine-induced Alzheimer’s disease model. These improvements suggest a possible mechanism through the inhibition of GSK-3β, which may contribute to the observed neuroprotective effects.</div></div><div><h3>Conclusion</h3><div>This study suggests that Plumbagin’s neuroprotective effects in scopolamine-induced Alzheimer’s disease may involve GSK-3β inhibition. Plumbagin shows significant therapeutic potential for Alzheimer’s treatment, warranting further investigation of its mechanism.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1859 ","pages":"Article 149650"},"PeriodicalIF":2.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of orexin receptor 2 plays anxiolytic effect in male mice","authors":"Lihua Chen ,&nbsp;Rui Tian ,&nbsp;Siqi Wei ,&nbsp;Hongwei Yang ,&nbsp;Chenchen Zhu ,&nbsp;Zicheng Li","doi":"10.1016/j.brainres.2025.149646","DOIUrl":"10.1016/j.brainres.2025.149646","url":null,"abstract":"<div><div>Anxiety disorders are the most common psychiatric illnesses. Present drugs can provide temporary relief for anxiety, however, they also come with side effects and safety concerns such as dependence, suicide, overdose and so on. Therefore, it is critical to discover new anxiolytic targets. An ongoing area of interest in the field of psychiatric diseases is the orexin system. Emerging body of evidences show that orexin receptor 1 (OX1R) has promising potential as novel anxiolytic target. However, little attention has been paid to orexin receptor 2 (OX2R) in anxiety. In this study, by using behavioral test, stereotaxic surgery and microinjection, virus-mediated knockdown of OX2R and pharmacological method, we found that: (1) Intraperitoneal injection of OX2R antagonist Seltorexant induced increased baseline anxiety-like behaviors in male mice. (2) Intraperitoneal injection of OX2R agonist YNT-185 reduced baseline anxiety-like behaviors in male mice. (3) Intraperitoneal injection of YNT-185 alleviated morphine withdrawal-induced anxiety-like behaviors in male mice. (4) Microinjection of YNT-185 into the VTA played anxiolytic effect in male mice. (5) Virus-mediated OX2R knockdown in the VTA induced anxiety-like behaviors in male mice.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1859 ","pages":"Article 149646"},"PeriodicalIF":2.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal drug delivery Dynamics: Extracellular and intracellular pathways revealed by Fluoro-Gold tracer in a mouse model","authors":"Meng-Ting Lin ,&nbsp;Tsai-Yun Chan ,&nbsp;Wei-Hao Liao ,&nbsp;Chueh-Hung Wu ,&nbsp;Tai-Horng Young ,&nbsp;Wen-Shiang Chen","doi":"10.1016/j.brainres.2025.149644","DOIUrl":"10.1016/j.brainres.2025.149644","url":null,"abstract":"","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1858 ","pages":"Article 149644"},"PeriodicalIF":2.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Okra-supplemented diet prevents hypothalamic inflammation in early overfeeding-programmed obese rats","authors":"Camila Luiza Rodrigues dos Santos Ricken ,&nbsp;Ginislene Dias ,&nbsp;Ingridys Regina Borkenhagen ,&nbsp;Adriano Nicoli Roecker ,&nbsp;Gisele Facholi Bomfim ,&nbsp;Hercules de Oliveira Costermani ,&nbsp;Aline Milena Dantas Rodrigues ,&nbsp;Nathalia Macedo Sanches ,&nbsp;Ester Vieira Alves ,&nbsp;Ricardo de Oliveira ,&nbsp;Júlio Cezar de Oliveira","doi":"10.1016/j.brainres.2025.149641","DOIUrl":"10.1016/j.brainres.2025.149641","url":null,"abstract":"<div><h3>Background</h3><div>Early overnutrition programs long-term metabolic dysfunctions. Owing to their benefits, functional foods have been used to treat metabolic diseases. We aimed to test the hypothesis that a diet supplemented with okra (<em>Abelmoschus esculentus</em> L.) mitigates energy metabolism impairment and glucose dyshomeostasis in early overfeeding-programmed rat offspring.</div></div><div><h3>Methods</h3><div>At postnatal Day 3, the litters were adjusted to 3 (small litter, SL) or 8 (normal litter, NL) pups. During lactation, milk collection and milk intake were performed. At 22 days-old, the pups were weaned and fed a standard diet (NL-SD and SL-SD groups) or an okra-supplemented diet (1.5 % <em>A. esculentus</em>; NL-AE and SL-AE groups). Body weight and food and water intake were measured every two days. Intraperitoneal glucose tolerance and intracerebroventricular insulin (10^-3 mmol/L) tests were performed, and then the offspring were euthanized. Blood, hypothalamus, and visceral fat pads were collected and lean body mass was measured.</div></div><div><h3>Results</h3><div>Milk from SL mothers had higher triglyceride and energy contents (P &lt; 0.05), and milk consumption by SL offspring was greater than that by NL rats. SL-SD rats were obese, hyperphagic, hypertriglyceridemic, hyperglycemic and glucose intolerant (P &lt; 0.05) and presented central insulin resistance and increased levels of hypothalamic proinflammatory [tumor necrosis factor alpha (TNF-α), 43.5 %; interleukin 6 (IL-6), 78.5 %; and interleukin 1 beta (IL-1β), 50.1 %, P &lt; 0.05] cytokines. On the other hand, the consumption of an okra-supplemented diet prevented all metabolic impairments.</div></div><div><h3>Conclusion</h3><div>In summary, dietary supplementation with okra prevents obesity and glucose deregulation in early-overfeeding rats, which is associated with improved hypothalamic inflammation and insulin resistance.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1858 ","pages":"Article 149641"},"PeriodicalIF":2.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term treatment with haloperidol modulates angiotensin I-converting enzyme (ACE) activity in transgenic animal model with construct validity for schizophrenia studies","authors":"William Y. Oyadomari ,&nbsp;Thays C. Santiago ,&nbsp;Leonardo Basso ,&nbsp;Vitor Oliveira ,&nbsp;Fábio C. Cruz ,&nbsp;João V. Nani ,&nbsp;Mirian A.F. Hayashi","doi":"10.1016/j.brainres.2025.149640","DOIUrl":"10.1016/j.brainres.2025.149640","url":null,"abstract":"<div><div>Elevated angiotensin I-converting enzyme (ACE) activity has been correlated with worse cognitive performance in patients with first-episode psychosis (FEP) and chronic schizophrenia (SZ). In this study, we investigated ACE activity in drug-naïve transgenic rats overexpressing the full-length non-mutated human <em>Disrupted-in-Schizophrenia 1</em> (<em>tg</em>DISC1) compared to wild-type (WT) controls, while we also assessed the effects of long-term treatment with typical antipsychotic haloperidol. Our findings indicated that untreated <em>tg</em>DISC1 rats show elevated serum ACE activity compared to WT animals, which is consistent with clinical observations in drug-naïve FEP patients. In contrast, baseline ACE activity in the brain of <em>tg</em>DISC1 was generally lower than in WT rats, with the exception of no difference in ACE activity observed in brain regions associated with learning, memory, and reward, such as the hippocampus and nucleus accumbens. Consistent with clinical observations in FEP patients following treatment with antipsychotics, 30-days of daily haloperidol-treatment significantly increased serum ACE activity in blood serum of both <em>tg</em>DISC1 and WT rats. However, ACE responses in brain were markedly different, as haloperidol treatment reduced ACE activity in most brain regions of both rat strains. These results support the existence of a central renin-angiotensin system (RAS) distinct from the peripheral RAS, suggesting that the treatment with a dopamine blocker exerts brain-specific effects on ACE activity, which was essentially opposite to that observed in the periphery. This region-specific alterations observed in cognition-related brain areas (notably with a relative stronger effect size in hippocampus and nucleus accumbens of <em>tg</em>DISC1 compared to WT rats) also suggest a critical interplay among dopamine homeostasis, ACE activity, and cognitive deficits in SZ. Understanding this interplay could help identifying novel biomarkers and/or therapeutic strategies for improving cognitive outcomes in SZ patients.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1859 ","pages":"Article 149640"},"PeriodicalIF":2.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baicalin liposomes ameliorate cerebral ischemia-reperfusion-induced acute lung injury by modulating the inflammatory response","authors":"Yu Long ,&nbsp;Xiaoqiu Li ,&nbsp;Xiaofang He ,&nbsp;Zaishan Wang ,&nbsp;Yuanyuan Wu ,&nbsp;Limiao Sun ,&nbsp;Yin Ma ,&nbsp;Jie Deng ,&nbsp;Yue Hu ,&nbsp;Nan Li","doi":"10.1016/j.brainres.2025.149642","DOIUrl":"10.1016/j.brainres.2025.149642","url":null,"abstract":"<div><div>Stroke is the leading cause of death globally, with stroke-associated pneumonia being a major contributor to its high mortality. Among these complications, cerebral ischemia–reperfusion injury-induced acute lung injury (CIR-ALI) is characterized by high morbidity and mortality rate, which causes a great economic burden to the society. The course of CIR-ALI is complex, in which the inflammatory cascade response plays a central role in the pathogenesis of CIR-ALI. Baicalin (BA), a flavonoid extracted from the natural plant <em>Scutellaria baicalensis</em>, exhibits diverse pharmacological effects, including anti-inflammatory and antioxidant properties. In this study, we investigated the therapeutic effects of baicalin and its delivery system baicalin liposome (BA-LP) on CIR-ALI injury. Using in vitro models of BV2 and Raw264.7 cells, as well as an in vivo model established via the wire bolus method, we measured inflammatory factors and pathological injuries in brain and lung tissues to evaluate the intervention effects of BA and BA-LP. In addition, the preliminary analysis of network pharmacology combined with experimental validation in this study preliminarily elucidated that BA and BA-LP may attenuate CIR-ALI by modulating the PI3K/AKT/mTOR pathway.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1859 ","pages":"Article 149642"},"PeriodicalIF":2.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotection in pentylenetetrazol kindling rat model: A synergistic approach with eugenol and photobiomodulation","authors":"Haitham S. Mohammed ,&nbsp;Dalia H. Ahmed ,&nbsp;Yasser A. Khadrawy ,&nbsp;Noha G. Madian","doi":"10.1016/j.brainres.2025.149645","DOIUrl":"10.1016/j.brainres.2025.149645","url":null,"abstract":"<div><div>Epilepsy is a complex neurological disorder characterized by recurrent seizures, significantly impacting patient health and quality of life. This study explores the neuroprotective effects of combining Eugenol (EUG), a natural bioactive compound administered at 100 mg/kg, with photobiomodulation (PBM), a non-invasive low-level laser therapy at 830 nm wavelength and 100 mW power, in a pentylenetetrazole (PTZ) kindling rat model of epilepsy. Fifty-nine adult male Wistar rats were assigned to five experimental groups: Control, PTZ (epilepsy model), PBM, EUG, and EUG + PBM. Seizure severity was assessed using a modified Racine scale following each PTZ injection. The study also evaluated cortical and hippocampal levels of brain-derived neurotrophic factor (BDNF), oxidative stress markers (MDA, NO, and GSH), activities of acetylcholinesterase (AChE) and Na + K + -ATPase, and monoamine neurotransmitters (DA, 5-HT, and NE). The results demonstrated that EUG and PBM, both individually and combined, significantly reduced seizure severity, mitigated oxidative stress, restored enzyme activities, and elevated BDNF levels. The combined treatment yielded superior neuroprotective effects compared to individual interventions, emphasizing its potential as a promising therapeutic strategy for epilepsy management.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1858 ","pages":"Article 149645"},"PeriodicalIF":2.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of HIF-1α silencing in late pregnancy hypoxia-induced autism-like behavior in rat offspring","authors":"Jinghua Tang,&nbsp;Ying Yang,&nbsp;Ping Qu,&nbsp;Jie Chen,&nbsp;Tingyu Li,&nbsp;Ying Dai","doi":"10.1016/j.brainres.2025.149633","DOIUrl":"10.1016/j.brainres.2025.149633","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can be caused by a variety of factors. Our previous study indicated that hypoxia-inducible factor 1 alpha (HIF-1α) plays a role in hypoxia-caused autism-like behavior. In this study, we investigated the mechanism by which HIF-1α contributes to prenatal hypoxia-induced autism-like behavior in vivo to provide an experimental basis for the treatment of ASD. We established a prenatal hypoxia model of pregnant rats by placing 17-day pregnant rats into a self-made hypoxia chamber filled with a nitrogen containing 10 %±0.5 % oxygen. Within 24 h after birth, the lateral ventricles of the prenatal hypoxia offspring rats were injected with a recombinant adeno-associated virus designed to silence HIF-1α expression. The autistic behavior of offspring rats in the HIF-1α silenced group was significantly alleviated compared with that of the prenatal hypoxia group. With the silencing of HIF-1α, the activity of phosphatase and tensin homolog (PTEN) increased and the PI3K/AKT pathway was inhibited by negative feedback. The mRNA expression level of vascular endothelial growth factor (VEGF) was decreased in the Si-HIF-1α silenced group and N-methyl D-aspartate receptor subtype 2 (NR2A) expression was downregulated. Thus, our study indicates that HIF-1α plays a role in hypoxia-induced autism-like behavior, and its regulatory effect may be achieved by inhibiting the activity of PTEN, resulting in activation of the PI3K signaling pathway. Synaptic plasticity regulation may also be involved.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1858 ","pages":"Article 149633"},"PeriodicalIF":2.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin protects mouse hippocampal neurons from neurotoxicity induced by amyloid β-peptide25–35","authors":"Karen del Carmen B. Salgado,&nbsp;Rosiene G.F. Nascimento,&nbsp;Ana Luiza S. Albuquerque,&nbsp;Laser A.M. Oliveira,&nbsp;Katiane de Oliveira Pinto Coelho Nogueira","doi":"10.1016/j.brainres.2025.149637","DOIUrl":"10.1016/j.brainres.2025.149637","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a complex neurodegenerative disorder and the leading cause of dementia in the elderly, as classified by the WHO. Its neuropathological hallmarks include the accumulation of amyloid-β (Aβ) plaques and intracellular tau tangles, which contribute to oxidative stress, mitochondrial dysfunction, lipid peroxidation, and neuronal death. Emerging evidence suggests that melatonin, a potent antioxidant produced by the pineal gland, plays a neuroprotective role in AD, yet its precise mechanisms remain underexplored. In this study, we utilized a physiologically relevant primary culture of hippocampal neurons to investigate melatonin’s protective effects against toxicity induced by Aβ25–35. Our findings demonstrate that melatonin significantly enhances cellular metabolism and viability while reducing reactive oxygen species (ROS) levels and lipid peroxidation, thereby mitigating Aβ-induced neurotoxicity. These results provide mechanistic insights into melatonin’s antioxidative and neuroprotective properties, reinforcing its potential as a therapeutic agent against oxidative stress in AD. This study underscores the promise of melatonin-based interventions in the development of novel antioxidant-targeted therapies for AD.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1859 ","pages":"Article 149637"},"PeriodicalIF":2.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Sensitivity and reliability of fNIRS to detect cochlear implant-induced auditory cortical activation in prelingually deaf children with inner ear malformation or cochlear nerve deficiency” [Brain Res. 1856 (2025) 149578]","authors":"Hiroshi Yamazaki ,&nbsp;Saburo Moroto ,&nbsp;Tomoko Yamazaki ,&nbsp;Rinko Tamaya ,&nbsp;Naoko Fujii ,&nbsp;Keizo Fujiwara ,&nbsp;Yasushi Naito","doi":"10.1016/j.brainres.2025.149615","DOIUrl":"10.1016/j.brainres.2025.149615","url":null,"abstract":"","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1857 ","pages":"Article 149615"},"PeriodicalIF":2.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}