Brain Research最新文献

Identification of potential inhibitors for MAP4K4 in glaucoma using Meta-Dynamics-Based dissociation free energy calculation. 利用基于元动力学的解离自由能计算，识别青光眼中 MAP4K4 的潜在抑制剂。

IF 2.7 4区医学

Brain Research Pub Date : 2024-11-03 DOI: 10.1016/j.brainres.2024.149300

Vanshika Rustagi, Rashmi Rameshwari, Indrakant Kumar Singh

{"title":"Identification of potential inhibitors for MAP4K4 in glaucoma using Meta-Dynamics-Based dissociation free energy calculation.","authors":"Vanshika Rustagi, Rashmi Rameshwari, Indrakant Kumar Singh","doi":"10.1016/j.brainres.2024.149300","DOIUrl":"https://doi.org/10.1016/j.brainres.2024.149300","url":null,"abstract":"<p><p>Glaucoma, a prevalent eye ailment causing irreversible vision loss, affects over 295 million individuals globally, necessitating the exploration of novel therapeutic avenues. Despite extensive research on targets like the phosphodiesterase enzyme and rho kinase, the potential of MAP4K4 in glaucoma remains untapped. This study aims to identify potent MAP4K4 inhibitors to counteract retinal cell apoptosis and oxidative stress associated with glaucoma. Using HTVS and XP docking, 911,059 compounds were screened. The MMGBSA calculation and pharmacokinetics analysis were used to shortlist the compounds. After performing 75 molecular dynamics simulations, further meta-dynamics were employed to calculate dissociation-free energy and find potential MAP4K4 inhibitors. Findings indicated that ZINC06717217 and ZINC38836256 exhibited remarkable promise, with docking scores of -9.57 and -11.12 and MMGBSA binding energies of -91.07 kcal/mol and -87.52 kcal/mol, respectively. Comparative analysis with the reference compound Q27453723 underscored their superior stability, requiring dissociation-free energies of -15.11 kcal/mol and -12.46 kcal/mol to disengage from the docked complex. This underscored their robust binding affinity. ZINC06717217 and ZINC38836256 show promising stability and strong binding to the MAP4K4 protein. Hence, these findings are promising in inhibiting MAP4K4 for glaucoma treatment, potentially leading to more effective treatment and curing blindness. KEY MESSAGES: First to incorporate the dissociation-free energy for identifying compounds for glaucoma treatment. In-silico analysis showed that ZINC06717217 and ZINC38836256 are promising compounds for targeting MAP4K4.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581610","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}

引用次数: 0

Astrocytic Gap Junctions protein Cx43/Cx30 modulate EAAT1 and glutamate to mediate cerebral ischemia-reperfusion injury. 星形胶质细胞间隙连接蛋白Cx43/Cx30调节EAAT1和谷氨酸，介导脑缺血再灌注损伤

IF 2.7 4区医学

Brain Research Pub Date : 2024-11-02 DOI: 10.1016/j.brainres.2024.149306

Min Li, Hongxia Nie, Qianqian He, Zhaoting Zhang, Shanhua Yu, Tiantian Wang, Bing Fu

{"title":"Astrocytic Gap Junctions protein Cx43/Cx30 modulate EAAT1 and glutamate to mediate cerebral ischemia-reperfusion injury.","authors":"Min Li, Hongxia Nie, Qianqian He, Zhaoting Zhang, Shanhua Yu, Tiantian Wang, Bing Fu","doi":"10.1016/j.brainres.2024.149306","DOIUrl":"https://doi.org/10.1016/j.brainres.2024.149306","url":null,"abstract":"<p><p>The gap connexins of astrocytes play a crucial role in facilitating neuronal coordination and maintaining the homeostasis of the central nervous system. Cx30/Cx43 are the main proteins constituting these gap junctions, and the glutamate transporter EAAT1 associates with nerve injury. However, the role and mechanism underlying the changes of astrocytic connexins and EAAT1 during cerebral ischemia-reperfusion injury remain unclear. In this study, we investigated the expressions of Cx30, Cx43, and EAAT1 in OGD/R-treated astrocytes and in a MCAO/R animal model using gap junction inhibitors and siRNAs targeting Cx43 and Cx30. The differences of cell viability, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reactive oxygen species (ROS) and glutamate in cells and tissues were detected. Our results indicate that OGD/R exposure leads to the decline of astrocyte activity, which, in turn, adversely affects neuronal health. Ischemia-reperfusion induced increasing Cx43 and EAAT1 expression and decreasing Cx30 expression in astrocytes and animal brain tissue. Moreover, ischemia-reperfusion resulted in heightened MDA and ROS levels and reduced CAT and SOD activities in both astrocytes and the surrounding brain tissue. The release of glutamate from astrocytes and its concentration in animal brain tissue significantly increased following ischemia-reperfusion. Inhibition Cx43 expression through Gap26 or siRNA effectively mitigated the increase in EAAT1 and glutamate levels, as well as the oxidative stress changes induced by ischemia-reperfusion. Therefore, Brain astrocytes may mediate the effects of cerebral ischemia-reperfusion injury by influencing glutamate transporters and glutamate dynamics in response to oxidative stress through Cx30/Cx43.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566828","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}

引用次数: 0

Altered callosal morphology in post stroke cognitive impairment. 中风后认知障碍中的胼胝体形态改变。

IF 2.7 4区医学

Brain Research Pub Date : 2024-11-02 DOI: 10.1016/j.brainres.2024.149307

Xiaoli Zhou, Huan Li, Tao Li, Zhao Ruan, Xiaohui Chen, Xitong Liu, Lei Gao, Haibo Xu

{"title":"Altered callosal morphology in post stroke cognitive impairment.","authors":"Xiaoli Zhou, Huan Li, Tao Li, Zhao Ruan, Xiaohui Chen, Xitong Liu, Lei Gao, Haibo Xu","doi":"10.1016/j.brainres.2024.149307","DOIUrl":"https://doi.org/10.1016/j.brainres.2024.149307","url":null,"abstract":"<p><p>Stroke is the second leading cause of death and cognitive impairment. Post-stroke cognitive impairment (PSCI) is one of the most common sequelae among stroke survivors, yet its underlying neural mechanisms remain largely unclear. The corpus callosum (CC) plays a crucial role in interhemispheric integration and hemispheric segregation, with changes in CC morphology potentially overlapping with the spectrum of PSCI. This study aimed to investigate the morphological changes in the CC and their diagnostic value in PSCI patients. Structural MRI, neurobehavioral, and clinical data were collected from 104 PSCI patients and 54 demographically matched healthy controls. Significant reductions in CC area, circularity, and genu thickness were observed in PSCI patients, with these changes strongly correlating with global cognitive function. Subgroup analysis revealed that CC circularity significantly decreased when lesions were located in the posterior circulation, while both CC area and circularity markedly decreased with anterior circulation lesions. Receiver Operating Characteristic analyses identified the midbody areas of the CC as having high diagnostic value, with area under the curve values of 0.748 and 0.746, respectively. Further validation analyses suggest that the transcallosal fibers in these CC subregions are connected to the premotor, dorsal attention, and frontoparietal system. These findings show that areal CC atrophy in PSCI patients, particularly in regions with transcallosal connections to the premotor cortex and frontoparietal network, parallels global cognitive impairment. This suggests that CC morphology may serve as a potential imaging marker for the diagnosis and prognosis of PSCI.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566819","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}

引用次数: 0

Pathophysiology of cerebral ischemia-reperfusion injury: An overview of oxidative stress and plant-based therapeutic approaches. 脑缺血再灌注损伤的病理生理学：氧化应激和植物治疗方法概述。

IF 2.7 4区医学

Brain Research Pub Date : 2024-11-02 DOI: 10.1016/j.brainres.2024.149308

Wasim Akhtar, Mohd Muazzam Khan, Sanjay Kumar, Usama Ahmad, Ali Husen, Shiirevnyamba Avirmed

{"title":"Pathophysiology of cerebral ischemia-reperfusion injury: An overview of oxidative stress and plant-based therapeutic approaches.","authors":"Wasim Akhtar, Mohd Muazzam Khan, Sanjay Kumar, Usama Ahmad, Ali Husen, Shiirevnyamba Avirmed","doi":"10.1016/j.brainres.2024.149308","DOIUrl":"https://doi.org/10.1016/j.brainres.2024.149308","url":null,"abstract":"<p><p>Stroke is a debilitating neurological disorder that causes substantial morbidity and mortality on a global scale. Ischemic stroke, the most common type, occurs when the brain's blood supply is interrupted. Oxidative stress is a key factor in stroke pathology, contributing to inflammation and neuronal cell death. As a result, there is increasing interest in the potential of plant extracts, which have been used in traditional medicine for centuries and are generally considered safe, to serve as alternative or complementary treatments for stroke. The plant extracts can target multiple pathological processes, including oxidative stress, offering neuroprotective effects. The development of highly efficient, low-toxicity, and cost-effective natural products is crucial for enhancing stroke treatment options. In this review, we examine 60 plant extracts that have been focused on the studies published from year 2000 to 2024 along with the studies' experimental models, dosages, and results. The plant extracts hold promise in modulating cerebral ischemia-reperfusion injury through counteraction of relevant pathophysiologic processes such as oxidative stress.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566897","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}

引用次数: 0

Intact ultrafast memory consolidation in adults with autism and neurotypicals with autism traits. 成人自闭症患者和具有自闭症特征的神经类型患者的完整超快速记忆巩固。

IF 2.7 4区医学

Brain Research Pub Date : 2024-10-30 DOI: 10.1016/j.brainres.2024.149299

Cintia Anna Nagy, Flóra Hann, Bianka Brezóczki, Kinga Farkas, Teodóra Vékony, Orsolya Pesthy, Dezső Németh

{"title":"Intact ultrafast memory consolidation in adults with autism and neurotypicals with autism traits.","authors":"Cintia Anna Nagy, Flóra Hann, Bianka Brezóczki, Kinga Farkas, Teodóra Vékony, Orsolya Pesthy, Dezső Németh","doi":"10.1016/j.brainres.2024.149299","DOIUrl":"https://doi.org/10.1016/j.brainres.2024.149299","url":null,"abstract":"<p><p>The processes of learning and memory consolidation are closely interlinked. Therefore, to uncover statistical learning in autism spectrum disorder (ASD), an in-depth examination of memory consolidation is essential. Studies of the last five years have revealed that learning can take place not only during practice but also during micro (<1 min) rests between practice blocks, termed micro offline gains. The concept of micro offline gains refers to performance improvements during short rest periods interspersed with practice, rather than during practice itself. This phenomenon is crucial for the acquisition and consolidation of motor skills and has been observed across various learning contexts. Numerous studies on learning in autism have identified intact learning but there has been no investigation into this fundamental aspect of memory consolidation in autistic individuals to date. We conducted two studies with two different samples: 1) neurotypical adults with distinct levels of autistic traits (N = 166) and 2) ASD-diagnosed adults (n<sub>ASD</sub> = 22, n<sub>NTP</sub> = 20). Participants performed a well-established probabilistic learning task, allowing us to measure two learning processes separately in the same experimental design: statistical learning (i.e., learning probability-based regularities) and visuomotor performance (i.e., speed-up regardless of probabilities). Here we show considerable individual differences in offline (between blocks) changes during statistical learning and between-blocks improvement during visuomotor performance. However, cumulative evidence from individual studies suggests that the degree of autistic traits and ASD status are not associated with micro offline gains, suggesting that, like statistical learning, rapid memory consolidation is intact.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563485","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}

引用次数: 0

Annexin A5 derived from lung alleviates brain damage after ischemic stroke. 源自肺部的附录蛋白 A5 可减轻缺血性中风后的脑损伤。

IF 2.7 4区医学

Brain Research Pub Date : 2024-10-29 DOI: 10.1016/j.brainres.2024.149303

Jiaxin Hu, Jiaqi Guo, Chuanjie Wu, Xiaoduo He, Jian Jing, Meimei Tao

{"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":"https://doi.org/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 levels 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 (FEV1) 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":null,"pages":null},"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}

引用次数: 0

Synergistic interaction between clonidine and ACPA on the modulation of anxiety-like behaviors in non-acute restraint stress and acute restraint stress conditions. 在非急性束缚应激和急性束缚应激条件下，氯尼丁和ACPA对焦虑样行为的调节具有协同作用。

IF 2.7 4区医学

Brain Research Pub Date : 2024-10-29 DOI: 10.1016/j.brainres.2024.149304

Amir Chitsaz, Mohaddeseh Ebrahimi-Ghiri, Mohammad-Reza Zarrindast, Fatemeh Khakpai

{"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, Mohaddeseh Ebrahimi-Ghiri, Mohammad-Reza Zarrindast, Fatemeh Khakpai","doi":"10.1016/j.brainres.2024.149304","DOIUrl":"https://doi.org/10.1016/j.brainres.2024.149304","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":null,"pages":null},"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}

引用次数: 0

Frontal alpha and parietal theta asymmetries associated with color-induced emotions 与颜色诱发情绪相关的额叶α和顶叶θ不对称。

IF 2.7 4区医学

Brain Research Pub Date : 2024-10-28 DOI: 10.1016/j.brainres.2024.149297

{"title":"Frontal alpha and parietal theta asymmetries associated with color-induced emotions","authors":"","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":null,"pages":null},"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}

引用次数: 0

Intermittent hypoxia-hyperoxia training ameliorates cognitive impairment and neuroinflammation in a rat model of Alzheimer's disease. 间歇性缺氧-过氧训练可改善阿尔茨海默病大鼠模型的认知障碍和神经炎症。

IF 2.7 4区医学

Brain Research Pub Date : 2024-10-28 DOI: 10.1016/j.brainres.2024.149301

Zoya Serebrovska, Lei Xi, Mykhailo Fedoriuk, Victor Dosenko, Angela Shysh, Michael Khetsuriani, Denys Porkhalo, Anton Savchenko, Serhii Goncharov, Natalie Utko, Sergii Virko, Victor Kholin, Egor Egorov, Roman Koval, Oksana Maksymchuk

{"title":"Intermittent hypoxia-hyperoxia training ameliorates cognitive impairment and neuroinflammation in a rat model of Alzheimer's disease.","authors":"Zoya Serebrovska, Lei Xi, Mykhailo Fedoriuk, Victor Dosenko, Angela Shysh, Michael Khetsuriani, Denys Porkhalo, Anton Savchenko, Serhii Goncharov, Natalie Utko, Sergii Virko, Victor Kholin, Egor Egorov, Roman Koval, Oksana Maksymchuk","doi":"10.1016/j.brainres.2024.149301","DOIUrl":"https://doi.org/10.1016/j.brainres.2024.149301","url":null,"abstract":"<p><p>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) Control group: received intracerebroventricular (ICV) injection of saline; 2) STZ group: received ICV injection of streptozotocin (STZ) to induce AD-like pathology; and 3) STZ + IHHT 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.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":null,"pages":null},"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}

引用次数: 0

Lindera aggregata improves intestinal function and alleviates depressive behaviors through the BDNF/TrkB/CREB signaling pathway induced by CUMS in mice Lindera aggregata 可通过 CUMS 诱导的 BDNF/TrkB/CREB 信号通路改善小鼠肠道功能并缓解抑郁行为

IF 2.7 4区医学

Brain Research Pub Date : 2024-10-28 DOI: 10.1016/j.brainres.2024.149295

{"title":"Lindera aggregata improves intestinal function and alleviates depressive behaviors through the BDNF/TrkB/CREB signaling pathway induced by CUMS in mice","authors":"","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":null,"pages":null},"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}

引用次数: 0