Shichao Pan , Yuxin Wen , Zhanhong Liu , Kaina Xu , Na Zhang , Xingbo Tong , Ye Teng , Xue Song , Xu Tong
{"title":"Neuroprotective effects of bone marrow mesenchymal stem cells combined with mannitol on radiation-induced brain injury by regulating autophagy via the PI3K/AKT/mTOR signaling pathway","authors":"Shichao Pan , Yuxin Wen , Zhanhong Liu , Kaina Xu , Na Zhang , Xingbo Tong , Ye Teng , Xue Song , Xu Tong","doi":"10.1016/j.brainresbull.2025.111326","DOIUrl":"10.1016/j.brainresbull.2025.111326","url":null,"abstract":"<div><h3>Background</h3><div>Bone marrow mesenchymal stem cells (BMSCs) have demonstrated potential in the treatment of radiation-induced brain injury (RIBI); however, the presence of the blood-brain barrier (BBB) limits their therapeutic efficacy. Additionally, the precise mechanisms behind the use of BMSCs in treating RIBI are still not well understood. This study aimed to investigate the therapeutic efficacy of mannitol and BMSCs on neuronal autophagy and their efficacy in treating RIBI.</div></div><div><h3>Methods</h3><div>In the study, RIBI models were first established in male Sprague-Dawley (SD) rats. Evans blue staining was performed to examine how mannitol influences BBB permeability in RIBI. We isolated BMSCs from SD rats using the whole bone marrow adherent method and assessed their adipogenic and osteogenic differentiation potential through Oil Red O and Alizarin Red S staining; flow cytometry analysis assessed cell surface markers. Prussian blue staining was employed to verify the migration of iron-labeled BMSCs into brain tissue. The rats were then divided into specific treatment groups, and model establishment followed according to experimental conditions. The body weight of the rats was measured weekly throughout the study. Cognitive function was assessed using the Morris water maze test. H&E and Nissl staining were applied to evaluate hippocampal neuronal survival. We quantified key proteins in the PI3K/AKT/mTOR signaling pathway by Western blotting, and quantified autophagy-related proteins LC3B and beclin-1 using both Western blotting and immunofluorescence.</div></div><div><h3>Results</h3><div>Mannitol treatment significantly increased BBB permeability and promoted BMSCs migration. The combination of BMSCs and mannitol improved cognitive and memory functions, leading to better body weight recovery compared to the BMSCs group. H&E and Nissl staining also revealed a significant increase in neuronal survival within the combined treatment group. Furthermore, we observed through Western blot and immunofluorescence analyses that combination of BMSCs and mannitol enhanced the activation of PI3K, AKT, and mTOR through phosphorylation, while it reduced the expression levels of LC3B and beclin-1.</div></div><div><h3>Conclusion</h3><div>The combination of BMSCs and mannitol treatment significantly improved cognitive function and hippocampal neuronal survival in RIBI rats. This effect was achieved by increasing BBB permeability, facilitating BMSCs migration to the injured region, and regulating excessive autophagy through the PI3K/AKT/mTOR pathway. This combined treatment demonstrated a neuroprotective effect superior to that of BMSCs treatment alone.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111326"},"PeriodicalIF":3.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143746646","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}
Xiaobo Yang , Kai Yao , Mengqi Zhang , Wenbin Zhang , Hengbing Zu
{"title":"New insight into the role of altered brain cholesterol metabolism in the pathogenesis of AD: A unifying cholesterol hypothesis and new therapeutic approach for AD","authors":"Xiaobo Yang , Kai Yao , Mengqi Zhang , Wenbin Zhang , Hengbing Zu","doi":"10.1016/j.brainresbull.2025.111321","DOIUrl":"10.1016/j.brainresbull.2025.111321","url":null,"abstract":"<div><div>The dysregulation of cholesterol metabolism homeostasis has been universally suggested in the aeotiology of Alzheimer's disease (AD). Initially, studies indicate that alteration of serum cholesterol level might contribute to AD. However, because blood-brain barrier impedes entry of plasma cholesterol, brain cells are not directly influenced by plasma cholesterol. Furthermore, mounting evidences suggest a link between alteration of brain cholesterol metabolism and AD. Interestingly, Amyloid-β proteins (Aβ) can markedly inhibit cellular cholesterol biosynthesis and lower cellular cholesterol content in cultured cells. And Aβ overproduction/overload induces a significant decrease of brain cellular cholesterol content in familial AD (FAD) animals. Importantly, mutations or polymorphisms of genes related to brain cholesterol transportation, such as ApoE4, ATP binding cassette (ABC) transporters, low-density lipoprotein receptor (LDLR) family and Niemann-Pick C disease 1 or 2 (NPC1/2), obviously lead to decreased brain cholesterol transport, resulting in brain cellular cholesterol loss, which could be tightly associated with AD pathological impairments. Additionally, accumulating data show that there are reduction of brain cholesterol biosynthesis and/or disorder of brain cholesterol trafficking in a variety of sporadic AD (SAD) animals and patients. Collectively, compelling evidences indicate that FAD and SAD could share one common and overlapping neurochemical mechanism: brain neuronal/cellular cholesterol deficiency. Therefore, accumulated evidences strongly support a novel hypothesis that deficiency of brain cholesterol contributes to the onset and progression of AD. This review highlights the pivotal role of brain cholesterol deficiency in the pathogenesis of AD. The hypothesis offers valuable insights for the future development of AD treatment.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111321"},"PeriodicalIF":3.5,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143746645","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":"Brain-thyroid crosstalk: 18F-FDG-PET/MRI evidence in patients with follicular thyroid adenomas","authors":"Yun-Ting Xiang , Jie Ma , Jia-Jia Wu , Xin Xue , Xin Gao , Xu-Yun Hua , Mou-Xiong Zheng , Jian-Guang Xu","doi":"10.1016/j.brainresbull.2025.111324","DOIUrl":"10.1016/j.brainresbull.2025.111324","url":null,"abstract":"<div><h3>Objective</h3><div>The hypothalamic-pituitary-thyroid axis has been well-known. However, whether follicular thyroid adenoma (FTA) could affect brain glucose metabolism is still unknown. Therefore, we explored the brain glucose metabolic characteristics of FTA with Fluorodeoxyglucose F18 positron emission tomography/magnetic resonance imaging.</div></div><div><h3>Methods</h3><div>Totally 30 FTA patients without clinical symptoms (FTA group), and 60 age- and sex-matched healthy controls (HC group) were included and randomly divided into cohort A and B in 2:1 ratio. Cohort A was analyzed with scaled sub-profile model/principal component analysis (SSM/PCA) for pattern identification. Cohort B was calculated the individual scores to validate expression of the pattern. Then we calculated the metabolic connectivity based on characteristics of the pattern to investigate the underlying mechanism. Finally, we constructed metabolic brain networks and analyzed the topological properties to further explore the brain metabolic model.</div></div><div><h3>Results</h3><div>In SSM/PCA, FTA group showed an almost global, left-right symmetrical pattern. In metabolic connectivity, FTA group showed increased metabolic connectivity in brain regions of the sensorimotor network, ventral default mode network (DMN), posterior salient network, right executive control network (ECN), visuospatial network and language network when compared to HC group, and showed decreased connectivity in dorsal DMN and left ECN. In topological properties of brain network, FTA group showed an increased betweenness centrality (BC) in left rolandic operculum, a decreased BC in superior temporal gyrus, increased BC and Degree in right precentral gyrus, increased D in right parahippocampal gyrus and left hippocampus, and decreased D and efficiency in right orbital part of middle frontal gyrus (FDR correction for multiple comparisons, <em>P</em> < 0.05).</div></div><div><h3>Conclusion</h3><div>Although FTA patients are not yet symptomatic, their brain metabolic characteristics include extensive brain alterations, disrupted internal connectivity, not only involving brain regions associated with endocrine activity, but also brain networks and regions associated with motor, emotion and cognition.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111324"},"PeriodicalIF":3.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725601","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}
Vikrant Pratap , Pratyush Kumar , Chethana Rao , Michael D. Gilchrist , Bharat B. Tripathi
{"title":"Modelling fourth-order hyperelasticity in soft solids using physics informed neural networks without labelled data","authors":"Vikrant Pratap , Pratyush Kumar , Chethana Rao , Michael D. Gilchrist , Bharat B. Tripathi","doi":"10.1016/j.brainresbull.2025.111318","DOIUrl":"10.1016/j.brainresbull.2025.111318","url":null,"abstract":"<div><div>Mild traumatic brain injury can result from shear shock wave formation in the brain in the event of a head impact like in contact sports, road traffic accidents, etc. These highly nonlinear deformations are modelled by a fourth-order Landau hyperelastic model, instead of the commonly used first or second order models like Neo-Hookean and Mooney-Rivlin models, respectively. The conventional finite element computational solvers produce robust and accurate estimates, yet they are not deployable for real-time prediction given the computational cost. The advent of physics-informed neural networks (PINNs) to solve partial differential equations (PDEs) has opened the possibility of real-time estimates of brain deformation. It involves developing a physics-informed neural network model that minimizes the residuals of the governing system of equations while ensuring boundary conditions are enforced. In this work, we propose a causal marching physics-informed neural network (CMPINN) model to capture the nonlinear mechanical response of higher-order hyperelastic materials. The CMPINN introduces a novel adaptive training scheme that incrementally updates the neural network weights. This approach incorporates several loss terms related to each material domain, boundary domain and internal domain that contributes to the total loss function, which is minimized during training. The proposed PINN framework is developed for a cube undergoing homogeneous isotropic incompressible canonical deformations: uniaxial tension/compression, simple shear, biaxial tension/compression, and pure shear. Three other tests for scenarios involving spatially varying material properties and inhomogeneous deformations are performed and benchmarked with analytical and numerical solutions.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111318"},"PeriodicalIF":3.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725599","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}
Xinmao Tian , Zishi Wang , Chunzhi Yi , Yuhua Shi , Chongchong Jia , Xiujuan Li , Feng Jiang , Zhenlong Wang
{"title":"Effects of basal division of posterior pallial amygdala on the motor behaviors in pigeons based on transcriptome analysis","authors":"Xinmao Tian , Zishi Wang , Chunzhi Yi , Yuhua Shi , Chongchong Jia , Xiujuan Li , Feng Jiang , Zhenlong Wang","doi":"10.1016/j.brainresbull.2025.111322","DOIUrl":"10.1016/j.brainresbull.2025.111322","url":null,"abstract":"<div><div>The basal division of posterior pallial amygdala (PoAb) was one important part of the amygdala in birds. PoAb mainly mediated turning behavior. However, the regulating neuromechanisms of PoAb in motor behavior was not clear yet. In this study, we selected septalis lateralis (SL) as the stimulated nucleus because it was closely associated with PoAb and had clear neuroregulatory functions, and we also used unrelated nuclei (entopallium) and unstimulated blank treatment (CK) as controls. We aim to study the neuroregulatory mechanisms of PoAb by investigating the differences of transcriptome level in different groups. A total of 622 differentially expressed genes (DEGs) were obtained from PoAb after comparing the SL stimulating group with the CK control group. GO functional annotation and KEGG pathway enrichment analysis showed that the upregulated 608 DEGs mainly involved energy supply and fluid balance. A total of 345 DEGs were obtained from the PoAb when comparing SL stimulation group and entopallium stimulation group. The upregulated 187 DEGs were mainly involved in cell communication and signal transductions. The study indicated that PoAb may modulate motor behaviour mainly by increasing ATP production and facilitating synaptic transmission, in which genes such as <em>SMAD3</em>, <em>TMED3</em>, <em>GRIA2</em>, <em>HTR1B</em> and <em>SNCG</em> play an important role. We revealed the mechanisms of brain regulation behaviour from gene level, and provided the theoretical foundation for understanding the avian brain.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111322"},"PeriodicalIF":3.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725600","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}
S. Ortega-Tinoco , M. Padilla-Orozco , F. Hernández-Vázquez , J. Garduño , A. Mondragón-García , E. Ramírez-Sánchez , J. Bargas , S. Hernández-López
{"title":"PACAP induces increased excitability in D1- and D2-expressing nucleus accumbens medium spiny neurons","authors":"S. Ortega-Tinoco , M. Padilla-Orozco , F. Hernández-Vázquez , J. Garduño , A. Mondragón-García , E. Ramírez-Sánchez , J. Bargas , S. Hernández-López","doi":"10.1016/j.brainresbull.2025.111323","DOIUrl":"10.1016/j.brainresbull.2025.111323","url":null,"abstract":"<div><div>One of the main eating disorders associated with overweight and obesity is binge eating disorder. Binge eating is characterized by excessive consumption of high-calorie foods over a short period of time, approximately 2 hours. The nucleus accumbens (NAc) plays a key role in modulating the hedonic value of high-calorie foods, commonly referred to as palatable foods. Specific subregions of the shell portion of the NAc (NAcSh), known as hedonic hot spots, may play an important role in the motivational aspect of food consumption. Previous work has shown that the pituitary adenylate cyclase-activating polypeptide (PACAP) injected into the NAc reduces palatable food intake, suggesting that this peptide could be a potential tool for treating binge eating. However, the mechanisms of action of PACAP on the NAc are poorly understood. Here, we used whole-cell recording and calcium imaging techniques in NAcSh brain slices from D1-Cre and A2A-Cre mice to investigate PACAP modulation of medium spiny neuron (MSN) activity. We found that PACAP administration increased the firing rate of D1- and D2-expressing MSNs. In addition, in a binge-eating mouse model, nasal PACAP reduced binge-eating behavior.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111323"},"PeriodicalIF":3.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728565","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}
Juan Li , Na Zhang , Wenjing Ren , Lan Li , Yi Sun , Yanyan Hou , Shuling Song , Lei Pan , Yunliang Sun , Kai Zhang , Dongze Li , Rongrong Guo , Changjun Lv , Fang Han , Yan Yu
{"title":"Effect of chronic intermittent hypoxia on hippocampal lipid metabolism in mice: A targeted lipidomics study","authors":"Juan Li , Na Zhang , Wenjing Ren , Lan Li , Yi Sun , Yanyan Hou , Shuling Song , Lei Pan , Yunliang Sun , Kai Zhang , Dongze Li , Rongrong Guo , Changjun Lv , Fang Han , Yan Yu","doi":"10.1016/j.brainresbull.2025.111319","DOIUrl":"10.1016/j.brainresbull.2025.111319","url":null,"abstract":"<div><div>Evidence suggests that cognitive impairments due to obstructive sleep apnea (OSA) are related to abnormal lipid metabolism. Abnormal lipid metabolism in the brain might be a potential cause of neurodegeneration. Nonetheless, there is limited clarity regarding the comprehensive lipid metabolism changes in the hippocampus induced by chronic intermittent hypoxia (CIH). Targeted lipidomic analysis of mouse hippocampus and HT22 cells was essential to exploring changes in lipid metabolism after CIH exposure. The approach was used to quantify 575 lipid species in mouse hippocampus and 1285 lipid species in HT22 cells, belonging to 6 different classes. Among those lipid classes, glycerophospholipids (GP), fatty acyls (FA), sphingolipids (SP), glycerolipid (GL), and prenol lipids (PR) were not significantly changed in mouse hippocampus under CIH conditions, but steroid (ST) levels were significantly reduced. Based on <em>in vitro</em> results, CIH exposure significantly raises the levels of several lipids, including GP, PR, SP, and ST. However, GL and FA did not change significantly. Notably, <em>in vivo</em> as well as <em>in vitro</em> experiments showed down-regulation of LPI (16:0), LPI (18:0), PC (18:1/20:4), PE (O-18:0/16:0), PE (O-16:0/22:6), PI (18:0/18:0), and up-regulation of PI (18:0/19:2). Additionally, in CIH conditions, lipid droplets (LDs) typically accumulate as a result of metabolism disorders. Disorders of lipid metabolism and the abnormal accumulation of LDs in neurons cause neuronal damage and behavioral disorders. The altered levels of LPI, PC, PE, and PI in OSA patients might provide new insights into understanding lipid metabolism disorders in the nervous system.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111319"},"PeriodicalIF":3.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728554","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":"Association of neurodegeneration, cognitive impairment, and short stature in Down syndrome; Could proinflammatory cytokines be the common factor?","authors":"Ghazaleh Sadeghi , Mohammad Hadi Farjoo","doi":"10.1016/j.brainresbull.2025.111317","DOIUrl":"10.1016/j.brainresbull.2025.111317","url":null,"abstract":"<div><div>Down syndrome (DS), caused by an extra copy of chromosome 21, is the most prevalent chromosomal disorder. It leads to various complications including, cardiac and endocrine dysfunctions, impairment of the immune system, growth retardation, and certain neurological conditions. Stunted growth in this population might be linked to an increased risk of a variety of co-occurring conditions, particularly neurological disorders. Studies indicate that the levels of neurodegeneration and neuroinflammation markers are higher in shorter children with DS. The disruption of insulin-like growth factor 1 (IGF1) signalling pathway due to the overexpression of proinflammatory cytokine genes could help establish a connection between short stature and neurodegeneration in DS. These cytokines disrupt the production of IGF1 in the liver, thereby inhibiting IGF1 from promoting bone and brain growth. Additionally, elevated cytokines levels impair the production of sex hormones by affecting the gonadal axis, further exacerbating the aforementioned conditions. The group of GnRH neurons responsible for cognitive functions is also impaired in DS, and treatment with GnRH agonists has demonstrated improvements in cognition. Although GnRH agonists can delay the fusion of growth plates by inhibiting pulsatile GnRH secretion, they may also lead to cognitive impairments. Hypothyroidism, the most prevalent endocrine complication of DS, can also contribute to both cognitive impairment and short stature. In conclusion, the increase of proinflammatory cytokines, through various mechanisms, can play a significant role in the development of both cognitive impairments and short stature in DS.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111317"},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727975","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}
Wei Liu , Xiao Chen , Chen Yang , Zequn Lin , Xinfeng Huang , Zhen Zhang , Jianjun Liu
{"title":"Preventive effects of xanthohumol in APP/PS1 mice based on multi-omics atlas","authors":"Wei Liu , Xiao Chen , Chen Yang , Zequn Lin , Xinfeng Huang , Zhen Zhang , Jianjun Liu","doi":"10.1016/j.brainresbull.2025.111316","DOIUrl":"10.1016/j.brainresbull.2025.111316","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a complex disease with unknown etiology and pathogenesis. We described a combined analysis of murine proteomics and microbiomics to find potential therapeutic targets of different doses of xanthohumol (Xn), with the goal of providing a biological basis for the treatment of early AD. Xn improved the spatial learning and memory ability of APP/PS1 mice; this was associated with an increased number of newborn neurons in the subgranular zone (SGZ) and dentate gyrus (DG) and a decreased inflammatory response. 108 proteins were significantly changed after 0.5 mg/kg Xn treatment while only 72 proteins changed by 5 mg/kg Xn. Eight significant microbiota were modulated by different doses of Xn at line discriminant analysis (LDA) score 3.0, but only three of which were regulated by 0.5 mg/kg Xn at LDA score 4.0. In addition, Xn treatment could significantly regulate the pathways of neurodegeneration- multiple diseases in the hippocampus and the penicillin and cephalosporin biosynthesis and atrazine degradation pathways in the gut. Interestingly, Nefl protein validated by correlation analysis was found in the common signaling pathway. 0.5 mg/kg Xn was able to reverse the correlation between hippocampal proteins and gut microbiota. Xn treatment significantly improved cognitive function in AD transgenic mice. Different doses of Xn caused significant differences in protein expression and flora composition and abundance, suggesting that the doses of Xn should be selected with caution, and low dose may be better in the prevention of AD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111316"},"PeriodicalIF":3.5,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705818","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}
Jessica L.S. Lima , Amanda R. Amaral , Ana Mayra de O. Cavalcante , Ana Kaline O. Chagas , Denise Nunes Oliveira , Juliana C. Melo , Gerlânia de O. Leite , Barry J. Sessle , Adriana R. Campos
{"title":"Anxiety- and nociception-like behaviours in mature adult mice induced by audiovisual overstimulation during infancy","authors":"Jessica L.S. Lima , Amanda R. Amaral , Ana Mayra de O. Cavalcante , Ana Kaline O. Chagas , Denise Nunes Oliveira , Juliana C. Melo , Gerlânia de O. Leite , Barry J. Sessle , Adriana R. Campos","doi":"10.1016/j.brainresbull.2025.111314","DOIUrl":"10.1016/j.brainresbull.2025.111314","url":null,"abstract":"<div><h3>Objectives</h3><div>To evaluate the behavioural effects in adult mice previously subjected to audiovisual overstimulation during infancy and adolescence.</div></div><div><h3>Methods</h3><div>Mice aged 21, 26 and 36 days (p21, p26 and p36) underwent auditory (70 db) and visual (flashing lights) stimulation for 2 or 6 h per day until p64; naive animals were used as controls. At p200, tests assessed respectively motor activity (open field test), depression (forced swimming and splash tests), anxiety (hole board, plus maze and marble burying tests, aggression (resident-intruder test), and nociception (von Frey and hot plate tests).</div></div><div><h3>Results</h3><div>There were no significant (ANOVA, p > 0.05) behavioural changes in forced swimming, splash, hole board, or marble burying tests between overstimulated and naive groups. However, the p21 group showed significantly (ANOVA, p < 0.05) increased anxiety-like behaviour (2 h) in the elevated plus maze test and altered nociceptive behaviour in the von Frey test (2 and 6 h). The p26 group (2 h) displayed significantly reduced rearing behaviours, fewer entries in the plus maze test, and faster reaction times to noxious thermal stimulation (2 h).</div></div><div><h3>Conclusion</h3><div>Audiovisual overstimulation during early development can promote anxiety-like behaviour and affect nociceptive behaviour in adult mice.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111314"},"PeriodicalIF":3.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696763","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}