Brain Research最新文献

{"title":"Annexin A5 derived from lung alleviates brain damage after ischemic stroke.","authors":"Jiaxin Hu, Jiaqi Guo, Chuanjie Wu, Xiaoduo He, Jian Jing, Meimei Tao","doi":"10.1016/j.brainres.2024.149303","DOIUrl":"10.1016/j.brainres.2024.149303","url":null,"abstract":"<p><p>Ischemic stroke is a leading cause of disability and death worldwide. It is now accepted that brain interacts bidirectionally with other organs after brain diseases. However, factors that might mediate crosstalk between brain and other organs are still less reported. Here we reported that plasma level of Annexin A5, not Annexin A1 or A2, was upregulated in stroke patients when compared to controls. In normal mice, the highest level of Annexin A5 were detected in lung tissues compared with other major organs and lowest level in brain. Moreover, Annexin A5 was increased in brain and decreased in lung after stroke in mice when compared to sham group. Fluorescence in situ hybridization (FISH) assay indicated that Annexin A5 could penetrate the blood-brain barrier (BBB). Treatment with Annexin A5 recombinant protein reduced the infarct volumes and improved neurological function after stroke in mice, while administration of anti-Annexin A5 increased the infarct sizes and aggravated neurological function. In a proof-of-concept analysis, patients with both ischemic stroke and lung diseases had a lower plasma Annexin A5 level than those with only ischemic stroke. Furthermore, Annexin A5 level in bronchoalveolar lavage fluid (BALF) was lower in patients with severe chronic obstructive pulmonary disease (COPD) when compared with those at a less severe grade of COPD, and level of Annexin A5 was positively correlated with forced expiratory volume in 1 s/prediction (FEV1pred) and PaO2. Our results suggest that Annexin A5 could alleviate infarct area and improve general neurological performance post cerebral ischemia. Increased Annexin A5 may derive from lung tissue and permeate across BBB to provide a neuroprotective function. Therefore, Annexin A5 may potentially serve as a therapeutic candidate for defending against IS-induced brain injury.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149303"},"PeriodicalIF":2.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557109","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":"Synergistic interaction between clonidine and ACPA on the modulation of anxiety-like behaviors in non-acute restraint stress and acute restraint stress conditions","authors":"Amir Chitsaz ,&nbsp;Mohaddeseh Ebrahimi-Ghiri ,&nbsp;Mohammad-Reza Zarrindast ,&nbsp;Fatemeh Khakpai","doi":"10.1016/j.brainres.2024.149304","DOIUrl":"10.1016/j.brainres.2024.149304","url":null,"abstract":"<div><div>The present research examined the possible role of α-2 adrenergic receptor drugs (clonidine, selective α-2 adrenergic receptor agonist, and yohimbine, competitive α-2 adrenoreceptor antagonist,) on the effect of arachidonylcyclopropylamide (ACPA), a cannabinoid CB1 receptor agonist, in non-acute restraint stress (NARS) and acute restraint stress (ARS) mice. The animals were unilaterally implanted with a cannula in the left lateral ventricle. ARS was carried out by movement restraint at a period of 4 h. An elevated plus-maze (EPM) apparatus was used to evaluate anxiety-like behaviors. The results indicated that induction of ARS for 4 h induced anxiogenic-like behavior due to the reduction of %OAT (the percentage of time spent in the open arms) in male mice. Additionally, ARS caused neuronal degeneration in the prefrontal cortex. On the other hand, alone intracerebroventricularly (i.c.v.) infusions of ACPA (0.5 µg/mouse) and clonidine (0.5 µg/mouse) increased %OAT, indicating an anxiolytic-like response in the NARS and ARS mice. In contrast, alone i.c.v. infusions of yohimbine (0.5 µg/mouse) decreased %OAT and %OAE (the percentage of entries to the open arms), proposing an anxiogenic-like effect in the NARS and ARS mice. When the subthreshold dose of ACPA and different doses of clonidine were co-injected, ACPA potentiated the anxiolytic-like behavior produced by clonidine in the ARS mice. On the other hand, when the ineffective dosage of ACPA and different dosages of yohimbine were co-infused, ACPA reversed the anxiogenic-like effect induced by yohimbine in the NARS and ARS mice. Moreover, the results revealed a synergistic effect between ACPA and clonidine upon induction of anxiolytic-like behaviors. It can be concluded that the interaction between clonidine and ACPA modulates the anxiety-like behaviors induced by stress in male mice.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1847 ","pages":"Article 149304"},"PeriodicalIF":2.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557110","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":"Frontal alpha and parietal theta asymmetries associated with color-induced emotions","authors":"Pablo Valdés-Alemán ,&nbsp;Bernarda Téllez-Alanís ,&nbsp;Diana Platas-Neri ,&nbsp;Bruma Palacios-Hernández","doi":"10.1016/j.brainres.2024.149297","DOIUrl":"10.1016/j.brainres.2024.149297","url":null,"abstract":"<div><div>This study investigates the relationship between color perception—hue, brightness, and saturation—and its emotional response—valence, arousal, and pleasure—, through subjective evaluations, as well as their association with frontal and parietal asymmetric activity patterns through electroencephalographic (EEG) recording. Using the 37 colors from the Berkeley Color Project, along with positive and negative control images, we examined the perceptual and emotional dimensions of color in 32 Mexican participants (19 women; <em>M</em> = 21.4 years, <em>SD</em> = 3.3). Subjective evaluations revealed a strong positive correlation between valence and brightness, and between arousal and saturation. Brighter, arousing, and pleasant colors were associated with greater cortical activation (decreased alpha power) in the left dorsolateral prefrontal region—i.e., F3 electrode—, indicating positive emotional processing according to the frontal alpha asymmetry model. Additionally, increased theta power in the right lateral parietal region—i.e., P4 electrode—correlated with higher positive emotional and pleasurable responses. Our findings are in line with studies suggesting universal consistencies in how perceptual color dimensions relate to emotional responses. Moreover, significant correlations between subjective emotional responses and asymmetrical EEG activity models are highlighted, providing insights into the neural mechanisms of color-induced emotion perception, as no other study has done before to our knowledge. Further research should explore these associations using higher spatial resolution imaging techniques and larger electrode arrays to define precise cortical and subcortical regions involved. These results contribute to understanding color perception’s impact on emotions, with potential applications in mental health treatments, such as chromotherapy for mood disorders.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149297"},"PeriodicalIF":2.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566868","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":"Intermittent hypoxia-hyperoxia training ameliorates cognitive impairment and neuroinflammation in a rat model of Alzheimer’s disease","authors":"Zoya Serebrovska ,&nbsp;Lei Xi ,&nbsp;Mykhailo Fedoriuk ,&nbsp;Victor Dosenko ,&nbsp;Angela Shysh ,&nbsp;Michael Khetsuriani ,&nbsp;Denys Porkhalo ,&nbsp;Anton Savchenko ,&nbsp;Serhii Goncharov ,&nbsp;Natalie Utko ,&nbsp;Sergii Virko ,&nbsp;Victor Kholin ,&nbsp;Egor Egorov ,&nbsp;Roman Koval ,&nbsp;Oksana Maksymchuk","doi":"10.1016/j.brainres.2024.149301","DOIUrl":"10.1016/j.brainres.2024.149301","url":null,"abstract":"<div><div>Alzheimer’s disease (AD), characterized by severe and progressive cognitive decline, stands as one of the most prevalent and devastating forms of dementia. Based on our recent findings showing intermittent hypoxic conditioning improved neuronal function in patients with mild cognitive impairment, the present study aimed at investigating whether the neuroprotective effects of intermittent hypoxia can be replicated in a rat model of AD, which allows us to explore the underlying cellular mechanisms involving neuroinflammation, hypoxia inducible factor 1α (HIF1α), and cytochrome P450 family 2 subfamily E member 1 (CYP2E1). Forty-one adult male Wistar rats were randomly assigned to three groups: 1) <em>Control</em> group: received intracerebroventricular (ICV) injection of saline; 2) <em>STZ</em> group: received ICV injection of streptozotocin (STZ) to induce AD-like pathology; and 3) <em>STZ + IHHT</em> group received ICV injection of STZ as well as 15 daily sessions of intermittent hypoxia-hyperoxia training (IHHT). We observed that ICV injection of STZ inhibited spatial learning and memory in the rats assessed with Morris Water Maze test. The cognitive function declines were accompanied by increased expression of amyloid β peptide (Aβ), HIF1α, CYP2E1, and TNFα in hippocampus. Interestingly, IHHT significantly restored the STZ-induced cognitive dysfunction, while reduced expression of Aβ, CYP2E1, HIF1α and TNFα. We conclude that IHHT with mild hypoxia-hyperoxia can enhance spatial learning and memory and reduce the AD-like pathologic changes in rats. The neuroprotective outcome of IHHT may be related to anti-inflammatory effects in hippocampus.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1847 ","pages":"Article 149301"},"PeriodicalIF":2.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543562","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":"Lindera aggregata improves intestinal function and alleviates depressive behaviors through the BDNF/TrkB/CREB signaling pathway induced by CUMS in mice","authors":"Xinliu Wang ,&nbsp;Xin Zhang ,&nbsp;Wei Xie ,&nbsp;Yuanyuan Wang ,&nbsp;Shuxian Zang ,&nbsp;Ziyun Ban ,&nbsp;Depei Li ,&nbsp;Yugai Jia ,&nbsp;Yonggang Gao","doi":"10.1016/j.brainres.2024.149295","DOIUrl":"10.1016/j.brainres.2024.149295","url":null,"abstract":"<div><div>Depression is a common mental illness, which is highly related to intestinal motor dysfunction and causes a global burden of disease. Lindera aggregata (LA), a traditional medicinal herb, has been used to treat gastrointestinal disorders; however, the effect of LA on depression remains unclear. Here, we assessed the impact of LA on chronic unpredictable mild stress (CUMS)-induced depression in mice and explored the related mechanisms. The results showed that LA ameliorated depressive behaviors in mice exposed to CUMS, as evidenced by improved performance in the sucrose preference test, force swimming test, and open field test, as well as increased serum levels of adrenocorticotropic hormone and 5-hydroxytryptamine. In addition, LA increased the serum levels of D-xylose and ghrelin, indicating that LA can promote gastrointestinal motility. Additional studies revealed that LA relieved CUMS-induced hippocampal tissue damage, as shown by hematoxylin and eosin and Nissl staining. LA increased the expression levels of brain-derived neurotrophic factor (BDNF) and promoted the activation of tropomyosin receptor kinase B (TrkB) and cAMP response element-binding (CREB) in the hippocampus of CUMS-exposed mice or in corticosterone-injured HT22 cells. In conclusion, LA can improve CUMS-induced depressive behavior in mice, potentially through hippocampal neuroprotection mediated by the BDNF/TrkB/CREB signaling pathway, which also contributes to improved intestinal function.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149295"},"PeriodicalIF":2.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553873","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":"Electroacupuncture extends the time window of thrombolytic therapy in rats by reducing disruptions of blood–brain barrier and inhibiting GSDMD-mediated pyroptosis","authors":"Huanhuan Liu ,&nbsp;Yiting Shen ,&nbsp;Zheng Huang ,&nbsp;Tao Jiang ,&nbsp;Peiyan Huang ,&nbsp;Mengning Yang ,&nbsp;Xinchang Zhang ,&nbsp;Wentao Xu ,&nbsp;Guangxia Ni","doi":"10.1016/j.brainres.2024.149296","DOIUrl":"10.1016/j.brainres.2024.149296","url":null,"abstract":"<div><h3>Objective</h3><div>Thrombolytic therapy is the primary treatment for acute ischemic stroke. Extending the therapeutic time window can effectively reduce the harmful side effects associated with thrombolytic therapy. Although electroacupuncture (EA) has been shown to extend this time window, the specific mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>We developed an embolic stroke model in rats and administered EA during thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) either 4.5 or 6 h after stroke onset. Neurological deficits were evaluated at 2 and 24 h post-stroke. Brain tissue was collected for analysis using 2,3,5-triphenyl tetrazolium chloride (TTC) staining, water content measurement, blood–brain barrier (BBB) permeability assessment, electron microscopy, and TUNEL assay. Immunofluorescence staining, western blotting, and enzyme-linked immunosorbent assays were employed to quantify the expression of proteins related to BBB integrity and pyroptosis.</div></div><div><h3>Results</h3><div>Neuronal damage and BBB disruption along with increased expression of pyroptosis-related proteins were observed following thrombolytic therapy at the 6-hour mark. EA treatment improved neurological outcomes, reduced infarct volume, and alleviated BBB disruption. EA also inhibited the expression of matrix metalloproteinase 9 (MMP9) and enhanced the expression of tissue inhibitor of metalloproteinases 1 (TIMP1), helping to maintain BBB integrity. Furthermore, EA reduced the expression of pyroptosis-related proteins, including gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18). EA also reduced the co-expression of GSDMD and MMP9 in brain tissues.</div></div><div><h3>Conclusions</h3><div>EA may be a promising therapeutic approach for extending the thrombolytic therapy window by protecting the BBB and inhibiting GSDMD-mediated pyroptosis.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1845 ","pages":"Article 149296"},"PeriodicalIF":2.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560695","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":"Cortical calretinin-positive neurons: Functional and ontogenetic characteristics and their relationship to brain pathologies","authors":"Lina Vanessa Becerra-Hernández ,&nbsp;Manuel F. Casanova ,&nbsp;Efraín Buriticá","doi":"10.1016/j.brainres.2024.149285","DOIUrl":"10.1016/j.brainres.2024.149285","url":null,"abstract":"<div><div>Cortical GABAergic interneurons can be classified according to electrophysiological, biochemical, and/or morphological criteria. In humans, the use of calcium-binding proteins allows us to differentiate three subpopulations of GABAergic interneurons with minimal overlap. Cortical calretinin-positive neurons mainly include bipolar and double-bouquet morphologies, with a largely non-rapid and adaptive firing pattern, originating from the ganglionic eminence and the ventricular and subventricular regions of the developing brain. These cells are distributed from layer I to VI of the neocortex, with predominance in layers II and III. Given their morphology, distribution of processes, and elucidated synaptic contacts, these neurons are considered important in the control of intraminicolumnar processing through vertical inhibition. They have been extensively studied in the context of pathologies characterized by excitation/inhibition imbalance, such as Alzheimer’s disease, epilepsy, traumatic brain injury, and autism. In light of the current evidence, this review considers these aspects in depth and discusses the pathophysiological role and selective vulnerability (pathoclisis) vs. the resistance that these interneurons can present against different types of injury.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1846 ","pages":"Article 149285"},"PeriodicalIF":2.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553872","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":"Quantitative synthetic MRI for evaluation of hippocampus in patients with multiple sclerosis","authors":"Jing Huang ,&nbsp;Yan Liang ,&nbsp;Jiyuan Wang ,&nbsp;Yi Shan ,&nbsp;Cheng Zhao ,&nbsp;Qiongge Li ,&nbsp;Huiqing Dong ,&nbsp;Jie Lu","doi":"10.1016/j.brainres.2024.149298","DOIUrl":"10.1016/j.brainres.2024.149298","url":null,"abstract":"<div><h3>Objective</h3><div>To identify early changes in hippocampal quantitative parameters in multiple sclerosis (MS) patients using synthetic MRI, and to correlate these changes with clinical variables.</div></div><div><h3>Methods</h3><div>45 MS patients and 26 healthy controls (HCs) underwent synthetic MRI and 3D-T1 MRI. The hippocampus volumes were assessed by using voxel-based morphometry. Synthetic MRI parameters (T1, T2, and proton density (PD)) from hippocampus and its subfield were measured and compared, and their associations with the Expanded Disability Status Scale (EDSS), Symbol Digit Modalities Test (SDMT) scores were further investigated.</div></div><div><h3>Results</h3><div>There was no significant difference in hippocampal volume between MS patients and HCs. Compared with HCs, the T1, T2 and PD values of hippocampus and its subfield increased in MS patients. T2 values showed positive correlation with EDSS and negative correlation with SDMT.</div></div><div><h3>Conclusions</h3><div>Synthetic MRI can detect subtle quantitative changes of the hippocampus in MS patients with normal hippocampal volume. Specifically, Synthetic MRI parameters may apply as potentially effective imaging biomarker for hippocampus evaluation.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1847 ","pages":"Article 149298"},"PeriodicalIF":2.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567008","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":"A coloaded liposome in situ gel as a novel therapeutic strategy to treat cerebral ischemia reperfusion injury","authors":"Qiang Tian ,&nbsp;Jin Li ,&nbsp;Rongbin Lv ,&nbsp;Guangan Zhou ,&nbsp;Xinyun Liu ,&nbsp;Yanfen Wang ,&nbsp;Baoliang Sun ,&nbsp;Zhangyong Xia","doi":"10.1016/j.brainres.2024.149292","DOIUrl":"10.1016/j.brainres.2024.149292","url":null,"abstract":"<div><h3>Background</h3><div>Ischemic stroke has become one of the leading causes of death and disability worldwide in individuals aged 60 and above. However, currently available drugs show limited efficacy. Therefore, research to find more effective and safer therapeutic strategies is an urgent requirement for the treatment of cerebral ischemia reperfusion injury (CIRI).</div></div><div><h3>Methods</h3><div>First, the free radical scavenger Edaravone and a Ginseng active ingredient were coloaded into liposomes (aER@Lip), followed by optimization and characterization. Pluronic F127 and F68 at different concentrations were mixed and stored at 4 °C for more than 24 h to obtain gel solutions. Then, aER@Lip was added to the gel solutions to prepare the drug-loaded <em>in situ</em> gel, termed aER@Lip-TSG.</div></div><div><h3>Results</h3><div><em>In vitro</em> experiments showed that aER@Lip-TSG was taken up by cells and had a good protective effect on oxygen-glucose deprivation/reoxygenation in pheochromocytoma 12 cells. In a rat CIRI model, aER@Lip-TSG delivered by intranasal administration not only decreased the apoptosis in brain tissue induced by CIRI, but also decreased the resultant inflammatory response. Moreover, the results suggested that aER@Lip-TSG had good biosafety.</div></div><div><h3>Conclusion</h3><div>This delivery system provides a promising multi-factor combination, synergistic effects, sustained-release capabilities, and is a non-invasive treatment strategy for CIRI. It thus meets the urgent need for effective treatments of central nervous system diseases.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1847 ","pages":"Article 149292"},"PeriodicalIF":2.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494949","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":"3,5-Dihydroxy-4-methoxybenzyl alcohol, a novel antioxidant isolated from oyster meat, inhibits the hypothalamus–pituitary–adrenal axis to regulate the stress response","authors":"Mitsugu Watanabe ,&nbsp;Kenji Yoshiike ,&nbsp;Emiko Miki ,&nbsp;Katsuya Kuroki","doi":"10.1016/j.brainres.2024.149290","DOIUrl":"10.1016/j.brainres.2024.149290","url":null,"abstract":"<div><h3>Background</h3><div>Antioxidants that can scavenge reactive oxygen in the brain and inhibit hyperactivity of the HPA axis are desirable.</div></div><div><h3>Aims</h3><div>We investigated the cerebral translocation of the antioxidant 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) and the effects of DHMBA administration on the hypothalamus–pituitary–adrenal (HPA) axis in stress-loaded rats.</div></div><div><h3>Methods</h3><div>Experiment 1: Plasma and brain DHMBA concentrations were measured over time after oral DHMBA administration to male B6 mice. Experiment 2: Female Wistar Imamichi rats were used. The normal group was not subjected to stress. The stress, DHMBA, and vitamin E groups were subjected to individual and overcrowding stress. Brain and hippocampal 8-hydroxy-2′-deoxyguanosine levels, hippocampal glucocorticoid receptor-α levels, plasma corticosterone levels and RNA levels of glutathione peroxidase 4, catalase, and glutathione reductase in the hippocampus were measured.</div></div><div><h3>Results</h3><div>In Experiment 1, DHMBA was not detected in the plasma or brain before DHMBA administration but was detected in both after administration. In Experiment 2, brain and hippocampal 8-hydroxy-2′-deoxyguanosine levels and plasma corticosterone levels were significantly lower in the DHMBA than in the stress group. Glucocorticoid receptor-α levels were higher in the DHMBA than in the stress group. DHMBA increased RNA levels of antioxidant enzymes in the hippocampus. <em>Conclusion</em>: DHMBA was translocated to the brain after administration. DHMBA administration decreased 8-hydroxy-2′-deoxyguanosine levels in the brain and hippocampus, increased hippocampal glucocorticoid receptor-α levels, and decreased the plasma corticosterone concentration, suggesting that DHMBA inhibits hyperactivity of the HPA axis. Nrf2 pathway activity induced by DHMBA resulted in increased antioxidant enzyme levels in the hippocampus.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1845 ","pages":"Article 149290"},"PeriodicalIF":2.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494948","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}