Brain Research Bulletin最新文献

{"title":"Neural mechanisms of tinnitus: An exploration from the perspective of varying severity levels","authors":"Jiapei Xie ,&nbsp;Weidong Zhang ,&nbsp;Yan Bai ,&nbsp;Wei Wei ,&nbsp;Yu Shen ,&nbsp;Wanyue Li ,&nbsp;Xinhui Wang ,&nbsp;Chen Yu ,&nbsp;Jiayin Pan ,&nbsp;Xiaodong Jia ,&nbsp;Hongjian Liu ,&nbsp;Meiyun Wang","doi":"10.1016/j.brainresbull.2025.111250","DOIUrl":"10.1016/j.brainresbull.2025.111250","url":null,"abstract":"<div><h3>Objective</h3><div>To compare the brain functional changes in tinnitus patients of varying severities, in order to elucidate the complex relationship between tinnitus symptoms and neural mechanisms, providing a basis for personalized treatment for tinnitus patients with varying severity levels.</div></div><div><h3>Method</h3><div>62 patients with chronic tinnitus were divided into severe and mild tinnitus group. 31 healthy controls (HC) matched for age, gender and education level were included. Resting-state functional magnetic resonance imaging was performed for all subjects, and the values of regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF) and functional connectivity (FC) were calculated. One-way analysis of variance (ANOVA) was used to compare the differences among the three groups. Correlational analysis was conducted between imaging metrics and clinical information.</div></div><div><h3>Results</h3><div>Compared to the mild tinnitus, the severe tinnitus shows increased ReHo and ALFF values in the left superior temporal gyrus (STG), middle temporal gyrus (MTG), supramarginal gyrus (SMG), angular gyrus (ANG), and middle occipital gyrus (MOG), as well as increased ReHo values in the left superior frontal gyrus (SFG) and ALFF values in the right ANG. In the severe tinnitus group, the FC between the bilateral ANG and the left MTG, the right ANG and the right medial SFG, the right ANG and the right anterior cingulate gyrus (ACG), as well as between the left SFG and the left rectus gyrus, was increased compared to the mild tinnitus group. In mild tinnitus group, the ReHo of left STG is correlated with tinnitus severity by Tinnitus Handicap Inventory.</div></div><div><h3>Conclusion</h3><div>Patients with different severity of tinnitus exhibit different compensatory mechanisms in brain function, highlighting the need for stratified analysis based on severity when investigating the underlying neural mechanisms.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111250"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405791","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":"The projection from the prelimbic cortex to the ventral tegmental area negatively regulates 5-HT-induced itch-scratching and positively regulates itch-related aversion in rats","authors":"Xing-Yu Lu ,&nbsp;Jun-Fei Teng ,&nbsp;Juan Yao ,&nbsp;Xuan Li ,&nbsp;Bing Wu ,&nbsp;Xue-Qiang Hu ,&nbsp;Ping Wang ,&nbsp;Xiao-Qian Jiang ,&nbsp;Jian-Feng Sui ,&nbsp;Ke-Hui Hu ,&nbsp;Yue-Ming Xu ,&nbsp;Shu-Lei Liu","doi":"10.1016/j.brainresbull.2025.111283","DOIUrl":"10.1016/j.brainresbull.2025.111283","url":null,"abstract":"<div><div>Direct and indirect evidence suggests that the prelimbic cortex (PrL) and the ventral tegmental area (VTA) are the key brain regions involved in the regulation of itch sensation and itch-related emotions. The PrL projects widely to various cortical and subcortical brain regions, with the VTA being one of the main targets of PrL descending projections. However, the differential roles of the PrL-VTA pathway in the regulation of itch sensation and itch-related emotion remain unclear. In this study, we investigated 5-HT-induced conditioned place aversion (CPA) and itch-scratching behavior in rats after pharmacogenetic inhibition of PrL-VTA projection activity. Pharmacogenetic inhibition of a subpopulation of PrL glutamatergic neurons projecting to the VTA increased 5-HT-induced itch-scratching behavior but alleviated the conditioned place aversion behavior accompanying acute itch, indicating that the descending pathway from the PrL to the VTA negatively controls itch sensation but positively regulates itch-related negative emotion. GABAergic and DAergic neurons in the VTA are potentially responsible for mediating the opposite regulatory effects of PrL-VTA projections on itch sensation and emotion, respectively. These results are helpful for further understanding the neuroregulatory mechanisms of different components of itch.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111283"},"PeriodicalIF":3.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527484","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":"The spatial and temporal pattern of GPER/GPR30 reporter expression in the developing and mature forebrain of mice","authors":"Meimei Wu ,&nbsp;Wenxin He ,&nbsp;Huashan Gong ,&nbsp;Li Dong ,&nbsp;Na Ding ,&nbsp;Guohua Zhang ,&nbsp;Jing Wang ,&nbsp;Weifang Rong","doi":"10.1016/j.brainresbull.2025.111276","DOIUrl":"10.1016/j.brainresbull.2025.111276","url":null,"abstract":"<div><div>Evidence suggest that estrogens play crucial roles in the regulation of neural development and function and the G protein-coupled estrogen receptor (GPER/GPR30) appears to be the predominant estrogen receptor in the brain. However, the distribution and functions of GPER in the developing and mature brain are not fully understood. The current study aimed to characterize the expression of GPER in the forebrain, using <em>Gper</em> gene reporter mice combined with fluorescent in situ hybridization (FISH/RNAscope) and immunohistochemistry (IHC). Two lines of <em>Gper</em> reporter mice were constructed by crossing the <em>Gper</em>-cre mice with Ai14(RCL-tdT)-D or R26-ZsGreen mice, which showed identical spatial distributions of the reporters in adult brain. In the forebrain, neurons, protoplasmic astrocytes, mural cells and ependymal cells of third ventricle, were found to express <em>Gper</em> reporters. GPER-expressing neurons were particularly enriched in the olfactory system and the salience network, including posteromedial nucleus of the cortical amygdala (PmCo), entorhinal cortex, insula cortex, prefrontal cortex and dentate gyrus of the hippocampus. RNAscope and neural tracing showed GPER-expressing cortical neurons were long-range excitatory pyramidal neurons. GPER-expressing astrocytes represented a minor population (&lt;10 %) of astrocytes and were found to be closely associated with neurovascular units. GPER-expressing mural cells were not labelled by the common pericyte marker PDGFRβ. In the critical period of neural development (P1-P10), GPER expression appeared to be intimately associated with neurogenesis, proliferation and migration in the olfactory system and the salience network. Collectively, the spatial and temporal pattern of GPER/GPR30 expression in the forebrain implied it might play important roles regulating the development and functions of the olfactory system, the salience network and the cerebral vessels.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111276"},"PeriodicalIF":3.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534092","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":"Expression pattern of Arc in the hippocampus of a rat model of epilepsy and depression comorbidity","authors":"Shiqian Yu,&nbsp;Hu Tuo,&nbsp;Baozhen Yao,&nbsp;Haiju Zhang,&nbsp;Fang Liu","doi":"10.1016/j.brainresbull.2025.111267","DOIUrl":"10.1016/j.brainresbull.2025.111267","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Two key factors associated with the comorbidity of epilepsy and depression (EAD), activity regulated cytoskeletal protein (Arc) and homer protein homolog 1 (Homer1), were previously identified by our group through bioinformatics methods (Yu et al., 2022). The expression of Arc and Homer1 were verified through animal experiments.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Six-week-old male specific pathogen-free grade Sprague Dawley rats (weighing 200 ± 20 g) received intraperitoneal injection of lithium chloride (LiCl)-pilocarpine for status epilepticus (SE) induction. SE was terminated after 30 min by intraperitoneal injection of diazepam, and spontaneous SE in rats was monitored by video for 2 weeks. The control group (Con group) was injected with an equal dose of sterile normal saline. Subsequently, EAD rats (EAD group) were selected from rat models of LiCl-pilocarpine-induced chronic epilepsy according to the immobility time of the forced swimming test on day 14 after LiCl-pilocarpine induced epilepsy. The remaining rats were included in the epilepsy group (EP group). Depression-like behaviors were evaluated using sucrose preference, open-field, and forced swimming tests. Body weight, sucrose preference percentage, the total distance of the open-field test, the average speed, the number of upright times, and the immobility time of the forced swimming test were assessed 14 and 28 days after LiCl-pilocarpine induced epilepsy. Rats in the EAD and EP groups were monitored by video for 2 weeks, and the frequency, grade, and duration of chronic spontaneous epileptic seizures were recorded. Epileptic seizures were compared between the EAD and EP groups. The expression of activity-regulated cytoskeletal protein (Arc) and Homer protein homolog 1 (Homer1) in the hippocampus of each group was detected by real-time quantitative PCR and western blot analysis. The fluorescence intensity of Arc in the hippocampus of each group was detected by immunofluorescence (IF) assay.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Compared with the Con and EP groups, rats in the EAD group exhibited a decreased body weight on day 28, a significant decrease in sucrose preference percentage on days 14 and 28, significantly extended immobility time, and significantly reduced total travel, average speed, the number of upright times. No significant differences in the number, grade, and duration of seizures were observed between the EAD and EP groups. Meanwhile, the expression level of Arc in the hippocampus was significantly decreased in the EAD group compared with the Con and EP groups; however, the expression level of Homer1 showed no significant change. IF results showed that Arc was mainly expressed in the cytoplasm, and the fluorescence intensity of Arc in hippocampal CA1, DG, and CA3 was lower in the EAD group than in the Con and EP groups.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;The expression of Arc in the hippocampal tissue of EAD rats is significantly","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111267"},"PeriodicalIF":3.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534093","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":"A systematic review of Phonological Components Analysis therapy studies for aphasia","authors":"Gregoire Python ,&nbsp;Edith Durand ,&nbsp;Michèle Masson-Trottier","doi":"10.1016/j.brainresbull.2025.111269","DOIUrl":"10.1016/j.brainresbull.2025.111269","url":null,"abstract":"<div><div>Among the wide range of anomia treatments for persons with aphasia (PWA), Phonological Components Analysis (PCA) is a well-known alternative. A systematic review of PCA efficacy studies for PWA was conducted to extract treatment-related and participant-related characteristics, to synthesise immediate and long-term outcomes and to assess the methodological quality of PCA studies (PROSPERO pre-registration CRD42024552047). Experimental studies on adults with post-stroke aphasia focusing on the efficacy of PCA published in English were included. Studies combining PCA with other treatment approaches, involving people with neurodegenerative disorders, without efficacy measures, or in dissertations, theses, and conference papers were excluded. The EBSCOhost platform and citations of the original PCA paper were last searched in November 2024. In total, thirteen studies were selected involving 89 PWA. Participants were at least 6 months post-stroke, and 75 % of them presented with Broca’s or anomic aphasia. The quality of PCA efficacy studies was relatively high according to the Single Case Experimental Design scale (mean 8.6 ± 1.0, range 7–10). Picture naming improved to reach at least a small effect size in 74 % of PWA (58/85) for trained items immediately after PCA and in 55 % of PWA (38/71) in the maintenance phase. Generalisation to untrained items occurred in 37 % of participants (22/59). Overall, PCA led to positive outcomes in the majority of PWA, which were often item-specific. As experimental designs were highly heterogeneous, further research is needed to better understand the optimal target population for PCA, the ideal dosage distribution, the key ingredients driving the improvement, and their neural correlates.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111269"},"PeriodicalIF":3.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522718","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":"Investigating mechanisms underlying the development of paralysis symptom in a model of MS","authors":"Shruti Gupta ,&nbsp;Sreejita Arnab ,&nbsp;Noah Silver-Beck ,&nbsp;Kayla L. Nguyen ,&nbsp;John R. Bethea","doi":"10.1016/j.brainresbull.2025.111275","DOIUrl":"10.1016/j.brainresbull.2025.111275","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder with approximately 80 % of patients suffering from pain and 50 % from paralysis. Using a rodent model for MS, experimental autoimmune encephalomyelitis (EAE), researchers have predominately investigated paralysis/motor disease as the clinical symptom of EAE with fewer studying MS/EAE pain. However, in EAE, all mice exhibit a pain like phenotype and only a subset progresses to paralysis. Despite extensive research characterizing the disease pathology, the etiology that contributes to the range of pain and motor symptom occurrence in MS remains understudied. This is the first study to dissect MS symptom pathophysiology, using the non-PTX EAE model, in mice that experience mechanical hypersensitivity (pain-like phenotype) with and without paralysis. We found that mechanical hypersensitivity experienced by mice with or without paralysis is comparable between the two groups, irrespective of sex. In addition, there is a significant increase in the activation and infiltration of immune cells, demyelination, and heightened protein expression of B cell chemoattractant CXCL13 within the spinal cord of mice exhibiting mechanical hypersensitivity and paralysis, compared to mice only experiencing mechanical hypersensitivity.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111275"},"PeriodicalIF":3.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511044","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":"FMRI insights into the neural alterations and clinical correlates in multiple sclerosis: A comprehensive overview of systematic reviews and meta-analyses","authors":"Sama Rahnemayan ,&nbsp;Arezoo Fathalizadeh ,&nbsp;Mehdi Behroozi ,&nbsp;Mahnaz Talebi ,&nbsp;Amirreza Naseri ,&nbsp;Elham Mehdizadehfar","doi":"10.1016/j.brainresbull.2025.111278","DOIUrl":"10.1016/j.brainresbull.2025.111278","url":null,"abstract":"<div><h3>Introduction</h3><div>Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammatory demyelination in the central nervous system. Functional Magnetic Resonance Imaging (fMRI) has emerged as an effective method for studying MS pathology. This review provides a comprehensive overview of fMRI applications, clarifying alterations in brain activity and identifying relevant biomarkers.</div></div><div><h3>Methods</h3><div>A systematic search of electronic databases and manual reference list checks at March 2024 yielded 470 articles. After duplicate removal, 456 articles underwent screening, 44 were assessed in full, and 12 systematic reviews and meta-analyses met inclusion criteria. Quality assessment was conducted.</div></div><div><h3>Results</h3><div>Included studies reported high methodological quality. fMRI revealed decreased functional connectivity within the default mode network, correlating with impaired information processing speed, and increased connectivity in compensatory networks during working memory tasks. Graph theory metrics identified disrupted global efficiency and clustering in functional networks, linked to gray matter atrophy. Neuroplasticity studies demonstrated cortical reorganization after cognitive rehabilitation, particularly in the prefrontal cortex. MS-related fatigue was associated with altered anterior cingulate cortex and thalamic activity, while depression correlated with reduced amygdala-prefrontal connectivity.</div></div><div><h3>Discussion</h3><div>fMRI has enhanced understanding of MS, revealing specific neural correlates of cognitive decline, neuroplasticity, fatigue, and depression. However, variability in MS subtypes and non-standardized protocols hinder consistency, while motion artifacts and cerebral blood flow changes complicate interpretation. Standardizing imaging protocols and integrating novel techniques could improve reliability and enable clinical applications to optimize patient monitoring and interventions.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111278"},"PeriodicalIF":3.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522721","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":"Unveiling causal relationships between tobacco use phenotypes and neuroimaging: Insights from bidirectional Mendelian randomization and bibliometric analysis","authors":"ZhaoTao Zhang ,&nbsp;LongTao Yang ,&nbsp;HuaFang Guan ,&nbsp;JiMan Shao ,&nbsp;ZhiJian Chen ,&nbsp;XinLan Xiao ,&nbsp;XiaoYong Wu","doi":"10.1016/j.brainresbull.2025.111277","DOIUrl":"10.1016/j.brainresbull.2025.111277","url":null,"abstract":"<div><div>Smoking is considered the most common addictive behavior worldwid. However, it is not systematically investigated whether there are bidirectional causal associations between tobacco use and neuroimaging, which might provide potential neural biomarkers or therapeutic neuro-targets for tobacco abuse or rehabilitation. In this study, using Mendelian randomization (MR), we explored both forward and reverse causal relationships between 4 tobacco use phenotypes (including Cigarettes per day, Smoking initiation, Age of initiation and Smoking cessation) and 209 neuroimaging features involving brain function and structure. Besides, we conducted a bibliometric analysis to find corresponding global trends of knowledge and specialized research areas. After Bonferroni correction, positive causal associations between cerebral global functional connectivity (FC) and smoking cessation, as well as between age of initiation and default mode network (DMN) structural connectivity (SC) were revealed; there were negative causal associations between mean diffusivity of left medial lemniscus and cigarette per day. Up to now, we also reveal that functional neuroimaging especially FC dominated smoking research field. Therefore, the discovery of causal relationships between smoking-related phenotypes and multi-modal cerebral alterations will promote a comprehensive understanding of tobacco addiction from cerebral function and structure perspective, facilitating the progression of personal treatment and risk prediction.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111277"},"PeriodicalIF":3.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522727","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":"Treadmill exercise ameliorates hippocampal synaptic injury and recognition memory deficits by TREM2 in AD rat model","authors":"Linlin Zhang ,&nbsp;Yanzhong Liu ,&nbsp;Xin Wang ,&nbsp;Hao Wu ,&nbsp;Jiahui Xie ,&nbsp;Yiping Liu","doi":"10.1016/j.brainresbull.2025.111280","DOIUrl":"10.1016/j.brainresbull.2025.111280","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;The impairment of cognitive function has been associated with Alzheimer’s disease (AD). Exercise exerts a positive modulatory effect on cognition by reducing synapse injury. However, limited in vivo evidence is available to validate the neuroprotective effect of TREM2 on synaptic function in this phenomenon. Here, we aim to explore whether physical exercise pretreatment alters Aβ-induced recognition memory impairment in structural synaptic plasticity within the hippocampus in AD rats.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods：&lt;/h3&gt;&lt;div&gt;In study 1, fifty-two Sprague-Dawley (SD) rats were randomly divided into following four groups: control group (C group, n = 13), Alzheimer’s disease group (AD group, n = 13), 4 weeks of physical exercise and Alzheimer’s disease group (Exe+AD group, n = 13), 4 weeks of physical exercise and blank group (Exercise group, n = 13). Four weeks of treadmill exercise intervention was performed, and AD model were established by intra-cerebroventricular injection (ICV) injection of Aβ&lt;sub&gt;1–42&lt;/sub&gt; protein. After 3 weeks, we also conducted a novel object test to evaluate recognition memory in the behavior assessment. Golgi staining and transmission electron microscopy were used to evaluate the morphology and synaptic ultrastructure of neurons. Western blotting was used to measure the expression of hippocampal synaptic proteins. Extracellular neurotransmitters in the hippocampus were detected by microdialysis coupled with high-performance liquid chromatography. In study 2, 33 SD rats were randomly divided into three groups: 4 weeks of physical exercise and Alzheimer’s disease group (Exe+AD group, n = 11), AAV-Control and physical exercise and Alzheimer’s disease group (AAV-Control+Exe+AD group, n = 11), AAV-TREM2 and physical exercise and Alzheimer’s disease group (AAV-TREM2 +Exe+AD group, n = 11). Stereotactic intracerebral injection in the bilateral hippocampus was performed to achieve microglial TREM2 down-expression by using adeno-associated virus (AAV) with CD68 promoter. After 4 weeks treadmill exercise and 3 weeks Aβ injection, all rats received behavior test and molecular experiment, which the same with experiment 2.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Novel recognition index in novel object recognition test significantly decreased, and western blot demonstrate that hippocampal TREM2 protein is significantly decreased (P &lt; 0.001). But physical exercise reversed this phenomenon(P &lt; 0.001). In addition, compared with Con group, the neuron from Exe+AD group exhibited a more complex branching pattern (P &lt; 0.05). And impaired synaptic ultrastructure was observed in AD group. Hippocampal synaptic-related protein (SYX, SYP, GAP43, PSD95) and neurotransmitter (DA, Glu, GABA) was also significantly decreased (P &lt; 0.01) in AD group. But the neuroprotection effect can be found in Exe+AD group, which are associated with the inhibition of synaptic injury by activate hippocampal TREM2 (P &lt; 0.05). How","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111280"},"PeriodicalIF":3.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522724","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":"A ketogenic diet decreases sevoflurane-induced burst suppression in rats","authors":"Morgan J. Siegmann ,&nbsp;Samuel Parry ,&nbsp;Arianna R.S. Lark ,&nbsp;Fayaz A. Mir ,&nbsp;Jinyoung Choi ,&nbsp;Abigail Hardy Carpenter ,&nbsp;Eliza A. Crowley ,&nbsp;Christian G. White ,&nbsp;Jiseung Kang ,&nbsp;Patrick L. Purdon ,&nbsp;Christa J. Nehs","doi":"10.1016/j.brainresbull.2025.111274","DOIUrl":"10.1016/j.brainresbull.2025.111274","url":null,"abstract":"<div><h3>Background</h3><div>The brain requires a continuous fuel supply to support cognition and can get energy from glucose and ketones. Dysregulated brain metabolism is thought to contribute to perioperative neurocognitive disorders and anesthesia-induced burst suppression. Therefore, we investigated the relationship between brain metabolites and neurophysiology during the behavioral states of sleep and anesthesia under a standard diet (SD) or a ketogenic diet (KD).</div></div><div><h3>Methods</h3><div>We measured prefrontal cortex glucose, lactate, and electroencephalogram in Fischer344 rats during spontaneous sleep/wake followed by 3 % sevoflurane anesthesia. Nine rats were fed a KD and 8 rats a SD. To assess the role of adenosine receptor-mediated ketone activity on burst suppression, 5 additional rats on the KD received an intraperitoneal injection of vehicle or the adenosine A1 receptor antagonist, DPCPX, before 3 % sevoflurane.</div></div><div><h3>Results</h3><div>Sevoflurane induced larger fluctuations in glucose (p &lt; 0.001) and lactate (p = 0.015) concentrations compared to sleep as measured by the standard deviation (glucose 0.085 mM and lactate 0.16 mM in sleep/wake and 0.25 mM and 0.41 mM during sevoflurane respectively). Changes in glucose and lactate were closely tied to electrophysiological oscillations. Animals on the KD had reduced burst suppression ratio (mean 10 % in KD vs 30 % in SD) (p = 0.007) as well as increased time to loss of movement (mean 14 min in KD vs 8 min in SD) (p = 0.003) compared to SD. DPCPX in KD rats showed a trend to increased burst suppression, reduced the time to start of burst suppression (45 min in KD+vehicle to 37 min KD+DPCPX) (p = 0.007), and increased duration of burst suppression (49 min in KD+vehicle to 90 min in KD+DPCPX) (p = 0.046) compared to KD+vehicle.</div></div><div><h3>Conclusions</h3><div>It is thought that anesthesia-induced burst suppression reflects an underlying deficiency in brain energy. Accordingly, we found that upregulating ketones, which increase available brain ATP levels, delayed anesthetic induction and decreased burst suppression consistent with the idea that the underlying metabolic state of the brain influences an anesthetic’s effect on the brain. These findings suggest that metabolic interventions could be useful therapeutic targets to modulate brain activity during sleep and anesthesia. Future studies will examine whether ketones can reduce the cognitive symptoms associated with postoperative delirium.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111274"},"PeriodicalIF":3.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514799","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}