Brain Research最新文献

{"title":"Long-term impact of congenital Zika virus infection on the rat hippocampus: Neuroinflammatory, glial alterations and sex-specific effects","authors":"Adriana Souza dos Santos ,&nbsp;Meirylanne Gomes da Costa ,&nbsp;Wellington de Almeida ,&nbsp;Gabrielle Batista de Aguiar ,&nbsp;Anna Luísa Lothhammer Bohn ,&nbsp;Ana Paula Rodrigues Martini ,&nbsp;Andrey Vinicios Soares Carvalho ,&nbsp;Thiago Ângelo Smaniotto ,&nbsp;Alessandra Schmitt Rieder ,&nbsp;Ana Paula Muterle Varelad ,&nbsp;Thais Fumaco Teixeirad ,&nbsp;Paulo Michel Roehe ,&nbsp;Angela Terezinha de Souza Wyse ,&nbsp;Carla Dalmaz ,&nbsp;Carlos Alexandre Netto ,&nbsp;Lenir Orlandi Pereira","doi":"10.1016/j.brainres.2024.149421","DOIUrl":"10.1016/j.brainres.2024.149421","url":null,"abstract":"<div><div>Congenital Zika Syndrome (CZS) is a condition that arises when a neonate presents with abnormalities resulting from Zika virus infection during gestation. While microcephaly is a prominent feature of the syndrome, other forms of brain damage are also observed, often accompanied by significant neurological complications. It is therefore essential to investigate the long-term effects of CZS, with special attention to sex differences, particularly concerning hippocampal function, given its vulnerability to viral infections. The aim of this study was to evaluate the long-term impacts on cognitive and memory functions, as well as neuroinflammatory and glial alterations in the hippocampus, in offspring of both sexes exposed to a model of congenital Zika virus infection. Pregnant rats were subcutaneously inoculated with ZIKV-BR at a dose of 1 × 10^7 plaque-forming units (PFU mL^-1) of ZIKV isolated in Brazil (ZIKV-BR) on gestational day 18 (G18). From postnatal day 70, the animals underwent behavioral tests. On postnatal day 80, the animals were euthanized, and hippocampal samples were collected for biochemical and histological analyses. In the open field test, females displayed more exploratory behavior and less grooming, while no significant differences in locomotion were observed between the sexes. Additionally, ZIKV-exposed females showed a reduction in grooming behavior compared to ZIKV-exposed males. In the memory test, males in the ZIKV group exhibited greater memory impairment, spending more time to locate the correct quadrant, while females showed relatively better performance. Neuroinflammatory markers, such as TNF-α, were significantly elevated in the hippocampus of ZIKV-exposed animals, regardless of sex. However, microglial and astrocytic responses, indicated by higher IBA1 and GFAP density, were only observed in male ZIKV rats. In conclusion, our findings suggest that congenital ZIKV exposure leads to sex-specific behavioral and neuroinflammatory alterations. While both males and females exhibited some behavioral changes, males were more significantly impacted in memory performance. Additionally, increased neuroinflammatory markers and glial activation were observed in the hippocampus of ZIKV-exposed animals, with a pronounced response in males. These results highlight the long-term impact of ZIKV infection on neurodevelopment, emphasizing the importance of considering sex differences in studies of congenital ZIKV syndrome.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149421"},"PeriodicalIF":2.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876167","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":"Asymmetric intra and inter-hemispheric subcellular rat brain correlation of arginyl-aminopeptidase activity during development and aging","authors":"Manuel Ramírez-Sánchez ,&nbsp;Isabel Prieto ,&nbsp;Ana Belén Segarra ,&nbsp;Inmaculada Banegas ,&nbsp;Magdalena Martínez-Cañamero ,&nbsp;Germán Domínguez-Vías ,&nbsp;Raquel Durán ,&nbsp;Francisco Vives","doi":"10.1016/j.brainres.2024.149417","DOIUrl":"10.1016/j.brainres.2024.149417","url":null,"abstract":"<div><div>The functional significance of brain asymmetry is still largely unknown. Studying the level of correlation of neuropeptide-degrading activities between subcellular fractions such as synaptosomal, of the left and right hemispheres of male rats during development and aging could provide relevant data on their functional role during these periods. The present study analyzes the level of correlation of a enkephalin- or angiotensin III-degrading activity, such as membrane-bound arginyl-aminopeptidase activity (M−B ArgAP) between the left versus right homogenate and/or synaptosomal subcellular fractions obtained and processed independently from both brain hemispheres during development and aging. The tested ages were: fetuses, rats of one week, one month, five month and two year old. In homogenate, the results demonstrate high levels of positive correlations (left versus right homogenate) with high levels of significance, without differences among the ages analyzed. In synaptosomes the results demonstrate positive correlations with a level close to statistical significance (left versus right synaptosomes) in fetuses, significant correlations at one week, one month and five months, particularly at one week and five months, and a radical decrease in the level of left versus right correlation between synaptosomes of two-year-old animals, which could suggest a functional loss of the bilateral synaptic interaction that could be carried out at earlier ages by M−B ArgAP activity. The interaction between left or right synaptosomes versus left or right homogenates demonstrate decreasing levels of positive correlation from fetuses to five month old rats, without differences between correlations of the left synaptosomes with correlations of the right ones. However, in two year old rats the values of correlations of the left synaptosomes diverged significantly from the right ones. While left synaptosomal correlations exhibited positive values, the right correlations exhibited negative ones, showing. a clear asymmetry between both sides in aged rats suggesting a marked reduction with aging of the synaptic function in the right hemisphere.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149417"},"PeriodicalIF":2.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876119","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":"Inhibition of autophagy attenuates cognitive decline and mitochondrial dysfunction in an Alzheimer’s disease mouse model with chronic cerebral hypoperfusion","authors":"Qin Yang ,&nbsp;Tingting Chen ,&nbsp;Shaofa Li ,&nbsp;Chengmin Yang ,&nbsp;Xingwu Zheng ,&nbsp;Sanying Mao ,&nbsp;Ning Liu ,&nbsp;Shenglong Mo ,&nbsp;Dengxing Li ,&nbsp;Meiling Yang ,&nbsp;Zhicheng Lu ,&nbsp;Lina Tang ,&nbsp;Xiaorui Huang ,&nbsp;Xia Liu ,&nbsp;Chongdong Jian ,&nbsp;Yixia Yin ,&nbsp;Jingwei Shang","doi":"10.1016/j.brainres.2024.149416","DOIUrl":"10.1016/j.brainres.2024.149416","url":null,"abstract":"<div><div>This study aimed to investigate the impact of chronic cerebral hypoperfusion (CCH) on cognitive function, amyloid-β (Aβ) deposition, cellular autophagy, and mitochondrial dynamics in an Alzheimer’s disease (AD) mouse model, and to evaluate the intervention effects of autophagy modulation on these outcomes. Utilizing the APP/PS1 mouse model combined with CCH, we assessed cognitive function, Aβ deposition, and the expression levels of relevant proteins through behavioral tests and immunohistochemical analysis. Our findings revealed pronounced cognitive deficits and increased Aβ deposition in the AD + CCH group mice, along with upregulation of mitochondrial fission proteins (Drp1, Fis1) and downregulation of mitochondrial fusion proteins (Opa1, Mfn1), indicating a shift towards mitochondrial fission and promoting cell apoptosis. Additionally, alterations were observed in the expression levels of cellular autophagy-related proteins (LC3-II, P62), which were reversed by treatment with autophagic inhibitor 3-methyladenine (3-MA). Furthermore, the expression of mitochondrial autophagy-related proteins PINK1 and Parkin was affected, with 3-MA alleviating this effect. In summary, our study elucidates the complex interplay among cognitive decline, increased Aβ deposition, and mitochondrial dysfunction in the AD + CCH model, and suggests that modulating autophagy could be a potential therapeutic strategy for treating the AD + CCH model.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149416"},"PeriodicalIF":2.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876125","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":"Kynurenine pathway dysregulation as a mechanistic link between cognitive impairment and brain damage: Implications for multiple sclerosis","authors":"Marie Kupjetz ,&nbsp;Tiffany Y. Wences Chirino ,&nbsp;Niklas Joisten ,&nbsp;Philipp Zimmer","doi":"10.1016/j.brainres.2024.149415","DOIUrl":"10.1016/j.brainres.2024.149415","url":null,"abstract":"<div><div>Cognitive impairment is a core symptom of multiple sclerosis (MS), resulting from inflammation-related brain damage and brain network dysfunction. Inflammation also causes dysregulation of the kynurenine pathway, which is the primary route of tryptophan metabolism. Kynurenine pathway dysregulation is characterised by a shift in concentrations of tryptophan catabolites, also referred to as kynurenines. Some kynurenines have neurotoxic effects that partly resemble the molecular mechanisms of MS pathophysiology underpinning brain damage and brain network dysfunction. The kynurenine pathway may therefore qualify as a mechanistic link between systemic inflammation, brain damage, and cognitive impairment in MS. This perspective article (1) provides an overview of inflammation-related kynurenine pathway dysregulation and MS-relevant neuroimmune properties of kynurenines and (2) summarises the current evidence on associations between systemic kynurenines, imaging metrics of brain structure or related markers, and cognitive performance in populations that present with kynurenine pathway dysregulation and are prone to cognitive impairment. These findings are used to (3) set a research agenda for future studies aimed at clarifying the role of the kynurenine pathway in brain damage and cognitive impairment in MS.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1853 ","pages":"Article 149415"},"PeriodicalIF":2.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876162","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}

{"title":"Cannabidiol induces autophagy via CB1 receptor and reduces α-synuclein cytosolic levels","authors":"Adolfo G. Erustes ,&nbsp;Vanessa C. Abílio ,&nbsp;Claudia Bincoletto ,&nbsp;Mauro Piacentini ,&nbsp;Gustavo J.S. Pereira ,&nbsp;Soraya S. Smaili","doi":"10.1016/j.brainres.2024.149414","DOIUrl":"10.1016/j.brainres.2024.149414","url":null,"abstract":"<div><div>Numerous studies have explored the role of cannabinoids in neurological conditions, chronic pain and neurodegenerative diseases. Restoring autophagy has been proposed as a potential target for the treatment of neurodegenerative diseases. In our study, we used a neuroblastoma cell line that overexpresses wild-type α-synuclein to investigate the effects of cannabidiol on autophagy modulation and reduction in the level of cytosolic α-synuclein. Our results demonstrated that cannabidiol enhances the accumulation of LC3-II- and GFP-LC3-positive vesicles, which indicates an increase in autophagic flux. In addition, cannabidiol-treated cells showed a reduction in cytosolic α-synuclein levels. These effects were inhibited when the cells were treated with a CB₁ receptor-selective antagonist, which indicates that the biological effects of cannabidiol are mediated via its interaction with CB₁ receptor. Additionally, we also observed that cannabinoid compounds induce autophagy and α-synuclein degradation after they interact with the CB₁ receptor. In summary, our data suggest that cannabidiol induces autophagy and reduces cytosolic α-synuclein levels. These biological effects are mediated preferentially through the interaction of cannabidiol with CB₁ receptors, and therefore, cannabinoid compounds that act selectively on this receptor could represent a new approach for autophagy modulation and degradation of protein aggregates.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149414"},"PeriodicalIF":2.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876121","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}

{"title":"The mechanism of different orexin/hypocretin neuronal projections in wakefulness and sleep","authors":"Nanxi Li ,&nbsp;Lishan Huang ,&nbsp;Bin Zhang ,&nbsp;Wenwen Zhu ,&nbsp;Wenbin Dai ,&nbsp;Sen Li ,&nbsp;Houping Xu","doi":"10.1016/j.brainres.2024.149408","DOIUrl":"10.1016/j.brainres.2024.149408","url":null,"abstract":"<div><div>Since the discovery of orexin/hypocretin, numerous studies have accumulated evidence demonstrating its key role in various aspects of neuromodulation, including addiction, motivation, and arousal. This paper focuses on the projection of orexin neurons to specific target brain regions through distinct neural pathways to regulate sleep and arousal. We provide a detailed discussion of the projection mechanisms of orexin neurons to downstream neurons, particularly emphasizing their activation of monoaminergic and cholinergic neurons associated with arousal. Additionally, we briefly explore the immune response and inflammatory factors linked to the loss of orexin neurons. Our findings underscore the significance of understanding specific neural projections in the generation and maintenance of arousal, which could guide advancements in neuroscience and lead to new therapeutic opportunities for treating insomnia or narcolepsy.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149408"},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871080","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}

{"title":"Theta-Gamma Decoupling – A neurophysiological marker of impaired reward processing in Parkinson’s disease","authors":"Rashi Sharma,&nbsp;Nivethida Thirugnanasambandam","doi":"10.1016/j.brainres.2024.149406","DOIUrl":"10.1016/j.brainres.2024.149406","url":null,"abstract":"<div><div>Individuals with Parkinson’s disease (PD) exhibit altered reward processing, reflected by a decreased amplitude of an event-related potential (ERP) marker called reward positivity (RewP). Most studies have used RewP to investigate reward behavior due to the high temporal resolution of EEG and its high sensitivity. However, traditional single-electrode ERP analyses often overlook the intricate dynamics of non-phase-locked oscillatory activity and the complex interactions within these neural oscillatory patterns. Studying oscillatory activity is crucial as it provides mechanistic insights into the functional, spatial, and temporal aspects of neuronal processing. To address this gap, we employed a data-driven approach to identify EEG-based markers associated with PD reward processing deficits. Using an openly available 64-channel EEG dataset of 28 age- and sex-matched PD and control participants during a reinforcement learning task, we conducted a comprehensive secondary analysis. First, we employed a cluster-based permutation method to extract ERP markers, finding a consistent decrease in reward positivity in PD, regardless of medication status. Additionally, through region of interest (ROI) analysis on time–frequency data, we identified specific oscillatory patterns during reward processing. PD patients exhibited attenuated theta power and increased gamma power compared to healthy controls (HC). Notably, within the PD group, those off medication showed anterior localization of high gamma power, while those on medication displayed higher posterior gamma power. Building upon these findings, we explored phase-amplitude coupling between theta phase and gamma amplitude measured by the modulation index. We observed a trend of decreased theta-gamma coupling in PD patients, with statistically significant differences between on and off medication conditions. These results highlight the potential role of theta-gamma coupling as a neuromodulatory target for improving goal-oriented behavior in PD. Our correlation analyses suggest that high gamma power is linked to longer disease duration, while reduced reward positivity and low theta-gamma coupling may serve as markers of the dopaminergic impact on reward processing. Thus, our study unveils the intricate time–frequency dynamics underlying reward processing deficits in PD, emphasizing the utility of a data-driven approach to elucidate neural mechanisms and to identify potential therapeutic targets.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149406"},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871254","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":"Effect of a single session of transcranial pulse stimulation (TPS) on resting tremor in patients with Parkinson’s disease","authors":"Paolo Manganotti ,&nbsp;Marco Liccari ,&nbsp;Tiziana Maria Isabella Lombardo ,&nbsp;Jacopo Della Toffola ,&nbsp;Valentina Cenacchi ,&nbsp;Mauro Catalan ,&nbsp;Pierpaolo Busan","doi":"10.1016/j.brainres.2024.149405","DOIUrl":"10.1016/j.brainres.2024.149405","url":null,"abstract":"<div><h3>Introduction</h3><div>Tremor is a common symptom in movement disorders and is evident at rest in Parkinson’s Disease (PD). In PD, tremor may be responsive to brain stimulation, ranging from Deep Brain Stimulation to Transcranial Magnetic Stimulation. Transcranial Pulse Stimulation (TPS) is a novel/painless/non-invasive technique which appears to induce biomolecular changes through shock waves. Here, as one of the first studies in the field of PD, we exploratively investigate the possibility to observe changes in tremor, induced by single-session TPS delivered on the motor cortex of PD patients.</div></div><div><h3>Methods</h3><div>TPS was delivered in 16 patients. Of these, 9 were admitted to sham (placebo). Resting tremor was measured at baseline (T0), after TPS (T1), and after 24 ​h from intervention (T2).</div></div><div><h3>Results</h3><div>At baseline, tremor was always present. After TPS, tremor reduction was noted at T1 and T2 (compared to T0 and placebo). We noted a decrease in the amplitude of resting tremor (not its frequency).</div></div><div><h3>Discussion</h3><div>TPS is a non-invasive technique that may be a novel solution for reducing tremor in PD, lasting at least 24 ​h after single-sessions. No side effects were reported. We discuss evidence suggesting potential physiological changes in mechanisms of neural circuits that are affected in PD.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149405"},"PeriodicalIF":2.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143131406","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}

{"title":"Effect of electroacupuncture on metabolic alterations in the hippocampus and dorsal raphe nucleus of Wistar Kyoto rats","authors":"Xiaoling Zeng ,&nbsp;Xuan Yin ,&nbsp;Kaiyu Cui ,&nbsp;Wenqing Xu ,&nbsp;Xiang Li ,&nbsp;Wei Zhang ,&nbsp;Wei Li ,&nbsp;Shifen Xu","doi":"10.1016/j.brainres.2024.149409","DOIUrl":"10.1016/j.brainres.2024.149409","url":null,"abstract":"<div><div>Depression is underpinned by a complex pathogenesis that involves the hippocampus and dorsal raphe nucleus (DRN) of the central nervous system. Although electroacupuncture (EA) is proven to be safe and effective for alleviating depression symptoms and causes minimal side effects, its underlying therapeutic mechanism remains unclear. In this study, we performed targeted metabolomics to identify metabolite alterations in the hippocampus and DRN of Wistar Kyoto (WKY) rats and elucidate the role and potential mechanism of action of EA. Our results indicated that 3 weeks of consecutive EA significantly ameliorated depression-like behaviors in WKY rats. Targeted metabolomics revealed 42 differentially expressed metabolites (DEMs) in the hippocampus and 97 DEMs in the DRN between Wistar and WKY rats. In addition, we observed 19 hippocampal DEMs and 41 DRN DEMs between WKY and EA-treated rats. Subsequent pathway analyses indicated that these DEMs were primarily enriched in amino acid-related metabolic pathways. Moreover, six DEMs were found to be significantly associated with at least one depression-like behavior, indicating their involvement in the pathogenesis of depression. EA intervention modulated the levels of 1-methylhistidine, 3-methylhistidine, carnosine, and riboflavin in depressed rats. Collectively, these findings demonstrate that disturbances in cerebral metabolites, especially amino acids, may be one of the causes underlying depression in WKY rats, and the therapeutic effect of EA is potentially mediated through the modulation of the levels of these metabolites.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149409"},"PeriodicalIF":2.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870823","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":"Lactobacillus casei Zhang prevents hippocampal atrophy and cognitive impairment in rats with type 2 diabetes by regulating blood glucose levels","authors":"Yue Cai ,&nbsp;Xuxia Wang ,&nbsp;Xi Chen ,&nbsp;Sijie Liu ,&nbsp;Linlin Cheng ,&nbsp;Yan Kang ,&nbsp;Fuchun Lin","doi":"10.1016/j.brainres.2024.149407","DOIUrl":"10.1016/j.brainres.2024.149407","url":null,"abstract":"<div><h3>Purpose</h3><div><em>Lactobacillus casei</em> Zhang (LCZ) has health benefits, such as the ability to improve blood glucose levels in individuals with type 2 diabetes mellitus (T2DM). However, little is known about the effects of LCZ on brain structural plasticity and cognitive function in T2DM. The aims of this study were to determine whether LCZ can prevent and alleviate brain damage and memory impairment in T2DM, and to understand the mechanisms underlying the effects of LCZ in T2DM.</div></div><div><h3>Methods</h3><div>Forty-one male Sprague-Dawley rats were divided into the saline control (CON, n = 14), T2DM (n = 14) and T2DM + LCZ (n = 13) groups. Magnetic resonance imaging (MRI) was used to evaluate alterations in brain structure among these three groups. The novel object recognition and Y-maze tests were conducted<!--> <!-->to assess cognitive function. Histological and immunohistochemical analysis, including Nissl staining, Golgi-Cox staining and glial fibrillary acidic protein immunostaining, were performed to explore the pathophysiological mechanisms underlying brain structural changes.</div></div><div><h3>Results</h3><div>T2DM rats presented hyperglycemia, cognitive decline, hippocampal atrophy, and damage to hippocampal neurons and astrocytes. Compared with those in the T2DM groups, rats in the T2DM + LCZ group presented lower blood glucose levels, better cognitive function, a larger hippocampal volume, and more normal hippocampal neurons and astrocytes. There was no significant difference in these metrics between rats in the T2DM + LCZ and CON groups.</div></div><div><h3>Conclusion</h3><div>Hyperglycemia-induced damage to hippocampal neurons and astrocytes may lead to hippocampal atrophy and cognitive dysfunction in T2DM. LCZ can effectively prevent this damage by regulating blood glucose levels, preventing brain atrophy and cognitive impairment in T2DM rats. These findings provide a scientific basis for the clinical application of LCZ.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149407"},"PeriodicalIF":2.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871079","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}