Metabolic brain disease最新文献

{"title":"Causal relationship between dyslipidemia and diabetic neuropathy: a mendelian randomization study.","authors":"Cong Li, Yu Feng, Lina Feng, Mingquan Li","doi":"10.1007/s11011-024-01448-y","DOIUrl":"10.1007/s11011-024-01448-y","url":null,"abstract":"<p><p>Some studies have shown an association between dyslipidemia and diabetic neuropathy (DN), but the genetic association has not been clarified. Therefore, the present study aimed to investigate the genetic causal association between dyslipidemia and DN through a Mendelian randomization (MR) approach. Genetic causal associations between total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) and DN were investigated by MR to provide a basis for the prevention and treatment of DN. Significant and independent single-nucleotide polymorphisms (SNPs) identified in genome-wide association studies were selected as instrumental variables (IVs) for MR analysis. Inverse variance weighted (IVW), MR‒Egger regression, weighted median (WME), simple mode (SM), and weighted mode (WM) methods were used to analyze causal associations. Heterogeneity and multiplicity tests were also performed and analyzed using the leave-one-out method to assess the stability of the results. Genetically predicted TC and DN (OR = 0.793, 95% CI = 0.655⁓0.961, P = 0.019) and LDL and DN (OR = 0.842, 95% CI = 0.711⁓0.998, P = 0.049) may be causally associated, but no causal associations were found between TG and DN (OR = 0.837, 95% CI = 0.631⁓1.111, P = 0.221) or between HDL and DN (OR = 1.192, 95% CI = 0.940⁓1.510, P = 0.149). TC and LDL may have genetic causal associations with DN, though no genetic causal associations were found for TG or HDL with DN. However, this study may have several limitations, and further clinical studies are needed to expand the sample size for future validation.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"78"},"PeriodicalIF":3.2,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895807","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":"Molecular intersections of traumatic brain injury and Alzheimer's disease: the role of ADMSC-derived exosomes and hub genes in microglial polarization.","authors":"Pengtao Li, Liguo Ye, Sishuai Sun, Yue Wang, Yihao Chen, Jianbo Chang, Rui Yin, Xiaoyu Liu, Wei Zuo, Houshi Xu, Xiao Zhang, Robert Chunhua Zhao, Qin Han, Junji Wei","doi":"10.1007/s11011-024-01503-8","DOIUrl":"10.1007/s11011-024-01503-8","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is a significant contributor to global mortality and morbidity, with emerging evidence indicating a heightened risk of developing Alzheimer's disease (AD) following TBI. This study aimed to explore the molecular intersections between TBI and AD, focusing on the role of adipose mesenchymal stem cell (ADMSC)-derived exosomes and hub genes involved in microglial polarization. Transcriptome profiles from TBI (GSE58485) and AD (GSE74614) datasets were analyzed to identify differentially expressed genes (DEGs). The hub genes were validated in independent datasets (GSE180811 for TBI and GSE135999 for AD) and localized to specific cell types using single-cell RNA (scRNA) sequencing data (GSE160763 for TBI and GSE224398 for AD). Experimental validation was conducted to investigate the role of these genes in microglial polarization using cell culture and ADMSC-derived exosomes interventions. Our results identified three hub genes-Bst2, B2m, and Lgals3bp-that were upregulated in both TBI and AD, with strong associations to inflammation, neuronal apoptosis, and tissue repair processes. scRNA sequencing revealed that these genes are predominantly expressed in microglia, with increased expression during M1 polarization. Knockdown of these genes reduced M1 polarization and promoted M2 phenotype in microglia. Additionally, ADMSC-derived exosomes attenuated M1 polarization and downregulated the expression of hub genes. This study provides novel insights into the shared molecular pathways between TBI and AD, highlighting potential therapeutic targets for mitigating neuroinflammation and promoting recovery in both conditions.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"77"},"PeriodicalIF":3.2,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882542","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":"Parkia biglobosa Jacq. (Locust Bean) leaves and seeds extracts attenuates diabetic-linked cognitive dysfunction in streptozotocin-induced male wistar rats.","authors":"Oluwapelumi M Ajiboye, Kayode O Ogunwenmo, Aderiike G Adewumi, Clinton C Mohanye","doi":"10.1007/s11011-024-01514-5","DOIUrl":"10.1007/s11011-024-01514-5","url":null,"abstract":"<p><p>Diabetes Mellitus is a metabolic disorder characterized by high blood glucose levels, causing significant morbidity and mortality rates. This study investigated the antidiabetic, neuroprotective, and antioxidant effects of ethanol extracts of Parkia biglobosa (PB) leaves and seeds in streptozotocin (STZ)-induced diabetic rats. The administration of STZ significantly elevated fasting blood glucose levels (FBGL) to 355-400 mg/mL compared to 111 mg/mL in normal controls, indicating hyperglycemia. Treatment with PB extracts at 100 mg/kg and 200 mg/kg significantly (p < 0.05) reduced FBGL in a dose-dependent manner. No significant difference was observed between the effects of metformin and PB extracts at 200 mg/kg. Cognitive dysfunction, assessed using the Y-maze test, was significantly improved in groups treated with PB extracts (p < 0.05), particularly at 200 mg/kg, through inhibition of cholinesterase activity and protection against oxidative damage. Both PB extracts also demonstrated significant inhibition (p < 0.05) of α-amylase and α-glucosidase activity, reducing postprandial hyperglycemia, with a stronger inhibition at 200 mg/kg. Additionally, PB extracts significantly increased catalase (CAT) and superoxide dismutase (SOD) activities, reversing the diabetes-induced decline in antioxidant enzyme levels. Monoamine oxidase (MAO) activity, elevated in diabetic conditions, was significantly downregulated by PB treatment, further contributing to neuroprotection. The neuroprotective effects may be attributed to the inhibition of cholinesterase and MAO, which help maintain neurotransmitter levels, alongside the antioxidant properties that mitigate oxidative stress in the brain. These findings suggest that PB extracts could serve as a natural therapeutic agent for diabetes management, with its effects comparable to metformin at higher doses.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"76"},"PeriodicalIF":3.2,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877596","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":"HMG-CoA reductase inhibitor simvastatin ameliorates trimethyltin neurotoxicity and cognitive impairment through reversal of Alzheimer's-associated markers.","authors":"Adel Salari, Mehrdad Roghani, Mohsen Khalili","doi":"10.1007/s11011-024-01515-4","DOIUrl":"10.1007/s11011-024-01515-4","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a prevalent neurodegenerative disorder in elderly. The neurotoxicant trimethyltin (TMT) induces neurodegenerative changes, as observed in AD. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor simvastatin (SV) has shown protective and promising therapeutic effects in neurological disorders such as AD and Parkinson's disease. The present study aimed to assess neuroprotective effect of simvastatin (SV) against trimethyltin (TMT) memory decline and hippocampal neurodegeneration. For inducing AD-like phenotype, rats were i.p. injected with TMT at 8 mg/kg and were treated with simvastatin daily for 3 weeks at 10 or 30 mg/kg. Our analysis of data indicated that simvastatin-treated TMT group has lower learning and memory deficits in behavioral tasks comprising Barnes maze, Y maze, and novel object discrimination (NOD). In addition, hippocampal inflammatory, oxidative, and apoptotic factors were attenuated besides reduction of acetylcholinesterase (AChE) activity and Alzheimer's pathology factors including presenilin-1 and hyperphorphorylated Tau (p-Tau) upon simvastatin. Moreover, simvastatin treatment of TMT group inverted hippocampal changes of Wnt, β-catenin, ERK, and Akt, ameliorated astrocytic and microglial reactivity, and also prevented injury of CA1 neurons. This study unraveled that simvastatin is capable to prevent TMT-induced Alzheimer's-like phenotype in association with Wnt/β-catenin/ERK/Akt as well as restraining hippocampal neurodegeneration.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"74"},"PeriodicalIF":3.2,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864834","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":"Lactobacillus fermentum MCC2760 attenuates neurobehavioral alterations induced by oxidized oils in rats.","authors":"Vyshali Keremane, Hamsavi Kamala, Prakash Halami, Ramaprasad Talahalli","doi":"10.1007/s11011-024-01509-2","DOIUrl":"10.1007/s11011-024-01509-2","url":null,"abstract":"<p><p>The common practice of reusing deep-fried oil may derange the ability of the brain to counter free radicals and inflammatory responses and can adversely alter neurobehavioral changes. In this study, we elucidated the modulatory potentials of Lactobacillus fermentum MCC2760 (LF) on neurobehavioral changes induced by dietary intake of oxidized oils. Female Wistar rats were fed with AIN-76 diets containing native sunflower oil (N-SFO), native canola oil (N-CNO), heated sunflower oil (H-SFO), heated canola oil (H-CNO), heated sunflower oil with probiotic (H-SFO + LF) or heated canola oil with probiotic (H-CNO + LF} for 60 days. After 60 days of feeding, they were mated with adult male rats. Upon mating confirmation, pregnant dams were continued on their respective diets until delivery. After delivery and post-lactation, F2 generation males (n = 6) were continued on a diet similar to their mothers for 60 days. Memory parameters [Morris water maze, Y-maze (spontaneous alteration), and novel object recognition test], locomotor skills and endurance (open field test and rotarod test), and anxiety test (elevated plus maze) were assessed in F2 generation males weighing 270 ± 10 g. Compared to their respective controls, heated oil-fed rats showed a significant (p < 0.05) decrease in memory and motor coordination skills, whereas a significant (p < 0.05) increase in anxiety-like behavior. However, administration of LF (10⁹ CFU/day/rat) ameliorated the heated oil-induced neurobehavioral changes. Hence, the present study establishes that long-term consumption of thermally oxidized oil is detrimental to critical brain functions, including cognitive attributes. Dietary supplementation of probiotics may effectively counter the oxidized oil-induced cognitive loss.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"75"},"PeriodicalIF":3.2,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864798","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":"Increased ROS levels, antioxidant defense disturbances and bioenergetic disruption induced by thiosulfate administration in the brain of neonatal rats.","authors":"Nícolas Manzke Glänzel, Nevton Teixeira da Rosa-Junior, Marian F Signori, Josyane de Andrade Silveira, Camila Vieira Pinheiro, Manuela Bianchin Marcuzzo, Cristina Campos-Carraro, Alex Sander da Rosa Araujo, Helgi B Schiöth, Moacir Wajner, Guilhian Leipnitz","doi":"10.1007/s11011-024-01510-9","DOIUrl":"10.1007/s11011-024-01510-9","url":null,"abstract":"<p><p>Sulfite oxidase deficiencies, either caused by deficiency of the apoenzyme or the molybdenum cofactor, and ethylmalonic encephalopathy are inherited disorders that impact sulfur metabolism. These patients present with severe neurodeterioration accompanied by cerebral cortex and cerebellum abnormalities, and high thiosulfate levels in plasma and tissues, including the brain. We aimed to clarify the mechanisms of such abnormalities, so we assessed the ex vivo effects of thiosulfate administration on energetic status and oxidative stress markers in cortical and cerebellar tissues of newborn rats. Thiosulfate (0.5 µmol/g) or PBS (vehicle) was injected into the fourth ventricle of rat pups. Thirty minutes after the injection, animals were euthanized and the brain structures were utilized for the experiments. Our data showed that thiosulfate decreased the reduced glutathione (GSH) concentrations, and superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) activities in the cortical structure. Thiosulfate also increased DCFH oxidation, hydrogen peroxide generation and glutathione reductase activity. In the cerebellum, thiosulfate reduced SOD and glutathione peroxidase activities but increased GST and CAT activities as well as DCFH oxidation. Regarding energy metabolism, thiosulfate specifically decreased complex IV activity in the cortex, whereas it increased cerebellar complex I and creatine kinase activities, indicating bioenergetic disturbances. The results suggest that the accumulation of thiosulfate causing redox disruption and bioenergetic alterations has a prominent role in the pathogenesis of sulfur metabolism deficiencies.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"73"},"PeriodicalIF":3.2,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864797","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":"Emerging role of Nrf2 in Parkinson's disease therapy: a critical reassessment.","authors":"Veerta Sharma, Prateek Sharma, Thakur Gurjeet Singh","doi":"10.1007/s11011-024-01452-2","DOIUrl":"10.1007/s11011-024-01452-2","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the neurodegenerative disorder characterized by the progressive degeneration of nigrostriatal dopaminergic neurons, leading to the range of motor and non-motor symptoms. There is mounting evidence suggesting that oxidative stress, neuroinflammation and mitochondrial dysfunction play pivotal roles in the pathogenesis of PD. Current therapies only alleviate perturbed motor symptoms. Therefore, it is essential to find out new therapies that allow us to improve not only motor symptoms, but non-motor symptoms like cognitive impairment and modulate disease progression. Nuclear factor erythroid 2-related factor 2 (Nrf2) is transcription factor that regulates the expression of numerous anti-oxidants and cytoprotective genes can counteract oxidative stress, neuroinflammation and mitochondrial dysfunction, thereby potentially ameliorating PD-associated pathology. The current review discusses about the Nrf2 structure and function with special emphasis on various molecular signalling pathways involved in positive and negative modulation of Nrf2, namely Glycogen synthase kinase-3β, Phosphoinositide-3-kinase, AMP-activated protein kinase, Mitogen activated protein kinase, nuclear factor-κB and P62. Furthermore, this review highlights the various Nrf2 activators as promising therapeutic agents for slowing down the progression of PD.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"70"},"PeriodicalIF":3.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854080","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":"Tribuli Fructus alleviates 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease by suppressing neuroinflammation via JNK signaling.","authors":"Jin Hee Kim, Eugene Huh, Hyeyoon Eo, Jin Se Kim, Youngji Kwon, In Gyoung Ju, Yujin Choi, Hae-Jee Yoon, So-Ri Son, Dae Sik Jang, Seon-Pyo Hong, Hi-Joon Park, Myung Sook Oh","doi":"10.1007/s11011-024-01498-2","DOIUrl":"10.1007/s11011-024-01498-2","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons. In particular, neuroinflammation associated with phosphorylation of c-Jun N-terminal kinase (JNK) is likely to cause the death of dopaminergic neurons. Therefore, protecting dopaminergic neurons through anti-neuroinflammation is a promising therapeutic strategy for PD. This study investigated whether Tribuli Fructus (TF) could alleviate PD by inhibiting neuroinflammation. Mouse primary mixed glial culture cells from the mouse cortex were treated with lipopolysaccharide (LPS) to induce neuroinflammation, and 1 h later, cells were treated with TF. 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) was injected into C57BL/6J mice for 5 days, and TF was co and post-administered for 12 days. Our study showed that TF attenuated pro-inflammatory mediators and cytokines in LPS-stimulated primary mixed glial cultures. In the brains of MPTP-induced PD mouse model, TF inhibited the activation of microglia and astrocytes, protected dopaminergic neurons, and increased dopamine levels. TF alleviated MPTP-induced bradykinesia, a representative behavioral disorder in PD. In addition, the results in vitro and in vivo revealed that TF regulates the phosphorylation of JNK. Collectively, our data suggest that TF may be a new therapeutic candidate for PD by regulating JNK signaling.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"69"},"PeriodicalIF":3.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854584","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":"Insights into risk factors and outcomes of post-stroke seizures in Saudi Arabia: a multicenter analysis.","authors":"Eman A Alraddadi, Yasser Alatawi, Raju S Kumar, Jawad I Bukhari, Abdulrahman E Alghamdi, Shahad Lughbi, Reema Alghamdi, Khalid Al Sulaiman, Faisal F Alamri","doi":"10.1007/s11011-024-01508-3","DOIUrl":"10.1007/s11011-024-01508-3","url":null,"abstract":"<p><p>Post-stroke seizures present a global challenge, yet its frequency and factors associated with its incidence are poorly documented, particularly in the Middle East. Thus, this study aims to investigate post-stroke seizure frequency and stroke-associated factors among ischemic stroke patients in Saudi Arabia, addressing demographic, clinical, and comorbid aspects to improve prognosis, diagnosis, prevention, and management. A multicenter, cohort observational study included eligible ischemic stroke patients who were categorized into those who developed seizures after injury and those who did not. Additionally, the study assessed the association between post-stroke seizure and 12-month mortality, 12-month stroke recurrence, and the occurrence of hemorrhagic transformation (HT) within 30 days. The study involved 1235 ischemic stroke patients, in which 13.5% developed post-stroke seizures. Patients with post-stroke seizures had more extended hospital stays, higher intensive care unit (ICU) admission rates, and a higher prevalence of comorbidities. Factors independently associated with post-stroke seizures included previous stroke history (OR = 1.93; 1.35-2.75), ICU admission (OR = 1.7; 1.15-2.5), and depression (OR = 2.1; 1.38-3.30). Logistic regression revealed associations between post-stroke seizures and HT (OR = 2.61; 1.70-4.00), stroke recurrence (OR = 2.30; 1.58-3.36), and mortality (OR = 1.89; 1.33-2.68). However, after adjusting for covariates, post-stroke seizures were significantly associated with stroke recurrence only (aOR = 1.7; 1.11-2.63). Our study identifies notable associations and risk factors for post-stroke seizures in ischemic stroke patients. This underscores the importance of adopting a comprehensive approach to stroke care to enhance the prediction, prevention, and management of post-stroke seizures. Further research is warranted to validate these findings, enhance the understanding of post-stroke seizure mechanisms, and guide management strategies.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"72"},"PeriodicalIF":3.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854366","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":"Pyridoxine supplementation before puberty ameliorates MAM-induced cognitive and sensorimotor gating impairments.","authors":"Cheng Xue, Xiao-Hui Li, Hong-Qun Ding, Xin Qian, Meng-Yu Zhang, Kai Chen, Zi-Wei Wei, Ying Li, Jun-Hai Jia, Wei-Ning Zhang","doi":"10.1007/s11011-024-01505-6","DOIUrl":"10.1007/s11011-024-01505-6","url":null,"abstract":"<p><p>Schizophrenia is a kind of neurodevelopmental mental disorder in which patients begin to experience changes early in their development, typically manifesting around or after puberty and has a fluctuating course. Environmental disturbances during adolescence may be a risk factor for schizophrenia-like deficits. As a better treatment option, preventive intervention prior to schizophrenia may be more beneficial than direct treatment. More effective stress-relieving interventions during the critical puberty period may prevent schizophrenia-like neuronal changes and the transition to schizophrenia in adulthood. Pyridoxine deficiency alters the function of NMDA (n-methyl-D-aspartic acid) receptors and plays a key role in learning and memory. In this study, we prepared a progeny model of schizophrenia by exposing pregnant rats to methoxymethanol acetate (MAM) on gestational day 17. The offspring rats were injected intraperitoneally with pyridoxine daily from birth to prepuberty PND12-PND21), and behavioral changes in the offspring rats were observed in adulthood. Cannabinoid receptor interacting protein 1 (CNRIP1) and cannabinoid receptor-1 (CB1R), which regulate memory, cognitive and motor activity, were detected in the prefrontal cortex (PFC) and hippocampus of the offspring rats, and the cell proliferation in the hippocampal dentate gyrus (DG) was also observed. The results showed that the MAM rats spent less time the open arm in the elevated plus maze test, decreased discrimination coefficient in novel object recognition test, and decreased prepulse inhibition, while the MAM rats supplemented with pyridoxine in prepuberty did not show any of the above abnormal behavioral changes in adulthood. By examining related proteins in the PFC and hippocampus, we found that only CB1R protein expression was downregulated in the PFC, whereas CNRIP1 expression was not only elevated in the hippocampus, but also significantly increased in pyridoxine- supplemented MAM rats. Meanwhile, pyridoxine supplementation alleviated the reduction of doublecortin (DCX)-positive cells and Ki67-positive cells in MAM rats. These results indicate that prepuberty pyridoxine supplementation has a positive effect on the prevention of cognitive deficits and sensorimotor gating impairment in MAM-induced schizophrenia-like rats, accompanied by changes in the CB1R and CNRIP1 expression in PFC and hippocampus, as well as the regeneration of neurons in the DG region.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"71"},"PeriodicalIF":3.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854563","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}