CEREBRAL CORTEX
·
2023
·
IF 3.7
Wan Changjian,Song Xueqing,Zhang Zhuyu,Hu Wenxiang,Chen Yanhua,Sun Wei,Liu Zhibin,Wang Songhua,Meng Wei
Physical exercise has been shown to have an impact on memory and hippocampal function across different age groups. Nevertheless, the influence and mechanisms underlying how voluntary exercise during puberty affects memory are still inadequately comprehended. This research aims to examine the impacts of self-initiated physical activity throughout adolescence on spatial memory. Developing mice were exposed to a 4-wk voluntary wheel running exercise protocol, commencing at the age of 30 d. After engaging in voluntary wheel running exercise during development, there was an enhancement in spatial memory. Moreover, hippocampal dentate gyrus and CA3 neurons rather than CA1 neurons exhibited an increase in the miniature excitatory postsynaptic currents and miniature inhibitory postsynaptic currents. In addition, there was an increase in the expression of NR2A/NR2B subunits of N-methyl-D-aspartate receptors and α1GABAA subunit of gamma-aminobutyric acid type A receptors, as well as dendritic spine density, specifically within dentate gyrus and CA3 regions rather than CA1 region. The findings suggest that voluntary exercise during development can enhance spatial memory in mice by increasing synapse numbers and improving synaptic transmission in hippocampal dentate gyrus and CA3 regions, but not in CA1 region. This study sheds light on the neural mechanisms underlying how early-life exercise improves cognitive function.
研究领域:
神经科学
·
行为学
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DOI
PubMed
高影响因子
Journal of Functional Foods
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2020
·
IF 3.701
Zhijie Bao,Penglin Zhang,Jin Chen,Jie Gao,Songyi Lin,Na Sun
This study was conducted to investigate possible mechanisms underlying egg yolk phospholipids on improving memory using scopolamine–treated mice and PC12 cells. Oral administration of egg yolk phospholipids significantly decreased latency in passageway water maze tasks and reduced error hits in passive avoidance tests for scopolamine–treated mice ( P < 0.05). As the results presented, egg yolk phospholipids attenuated spatial memory deficits via preventing region–specific lesions in hippocampus CA1-2 and regulating the activity of cholinergic biomarkers. Egg yolk phospholipids significantly inhibited scopolamine–induced increase of acetylcholinesterase activity and decrease of choline acetyltransferase activity ( P < 0.05), thus maintaining the release of acetylcholine at a normal level. Further analysis showed that egg yolk phospholipids downregulated scopolamine–induced MAO activity and MDA level in PC12 cells ( P < 0.05). These data suggest that egg yolk phospholipids might exert neuroprotective effects via attenuating cholinergic damage and inhibiting the oxidative stress in vitro .
研究领域:
神经科学
·
药理学
·
营养科学
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产品关联
DOI
高影响因子
Environment & Health
·
2025
·
IF 6.3
Nanxi Bi,Chengqing Huang,Xiaozhen Gu,Rongrong Wang,Haoyu Liu,Ruiqing Zhou,Heyujia Zhang,Xiang-Tao Chen,Hui-Li Wang
Bisphenol A (BPA) exposure can impair learning and memory in rodents, but the underlying systematic neural mechanism remains unclear. Due to the important role of the hippocampus for learning and memory, in this study, we systematically investigated the neural circuit, neuron structure, and function of the hippocampus after BPA exposure. First, by employing a virus tracing technique, we observed a decrease in the neural projection ratio of excitatory neural neurons from the “Entorhinal Cortex-Dentate Gyrus-CA3-CA1” and “Entorhinal Cortex-CA1” circuits. Furthermore, BPA exposure led to impairments of the branching complexity and electrophysiological properties of hippocampal neurons. Additionally, fiber photometry experiments revealed that BPA exposure reduces the level of real-time activity in hippocampal excitatory neurons (CA1, CA3, and DG) during the MWM task. To verify the role of hippocampal excitatory neurons in learning and memory impairment caused by BPA, the dorsal hippocampus CA1 neurons were chemogenetically activated, and the spatial memory deficits were rescued. Collectively, our results suggest that BPA exposure impairs the hippocampal neural circuits and neuronal real-time response, leading to the dysfunction of spatial memory in mice. This study expands our understanding of the neurotoxic mechanisms of BPA at the mesoscopic neural level and provides a potential strategy for rescuing BPA-induced learning and memory impairments.
研究领域:
神经科学
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毒理学
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认知科学
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环境健康
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Brain Sciences
·
2024
·Vol. 14
·期 4
·327
·
IF 2.7
Yuhan Wu,Hui Hu,Weiwei Liu,Yun Zhao,Fang Xie,Zhaowei Sun,Ling Zhang,Huafeng Dong,Xue Wang,Lingjia Qian
Lactate has emerged as a key player in regulating neural functions and cognitive processes. Beyond its function as an energy substrate and signal molecule, recent research has revealed lactate to serve as an epigenetic regulator in the brain. However, the molecular mechanisms by which lactate regulates spatial memory and its role in the prevention of cognitive disorders remain unclear. Herein, we injected L-lactate (10 μmol/kg/d for 6 d) into the mouse’s hippocampus, followed by the Morris water maze (MWM) test and molecular analyses. Improved spatial memory performances were observed in mice injected with lactate. Besides, lactate upregulated the expression of synaptic proteins post-synaptic density 95 (PSD95), synaptophysin (SYP), and growth associated protein 43 (GAP43) in hippocampal tissues and HT22 cells, suggesting a potential role in synaptic transmission and memory formation. The facilitative role of monocarboxylate transporter 2 (MCT2), a neuron-specific lactate transporter, in this process was confirmed, as MCT2 antagonists attenuated the lactate-induced upregulation of synaptic proteins. Moreover, lactate induced protein lactylation, a post-translational modification, which could be suppressed by MCT2 inhibition. RNA sequencing of lactated-injected hippocampal tissues revealed a comprehensive gene expression profile influenced by lactate, with significant changes in genes associated with transcriptional progress. These data demonstrate that hippocampal lactate injection enhances spatial memory in mice, potentially through the upregulation of synaptic proteins and induction of protein lactylation, with MCT2 playing a crucial role in these processes. Our findings shed light on the multi-faceted role of lactate in neural function and memory regulation, opening new avenues for therapeutic interventions targeting cognitive disorders.
研究领域:
神经科学
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认知科学
·
分子生物学
·
表观遗传学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2022
·
IF 7.419
Yuanyuan Zhang,Qian Li,Chunqing Wang,Lin Zhu,Furun Wang,Wencheng Jiao,Xiaomei Zhuang,Fei Xie,Lina Du,Yiguang Jin
Microwave is commonly used in the life, manufacturing and military fields, which may induce body injuries. Brain is the major target organ of microwave radiation and microwave-induced brain injury (MIBI) can lead to insomnia, dreaminess, and a decline in learning and memory. However, there is no clinical medications are available currently. Calcium channel blockers may protect the brain tissue from microwave but most of them cannot enter the brain. Here, we selected a calcium channel blocker-cinnarizine to prepare its dissolving microneedles (MNs) for the therapy of MIBI. The cinnarizine MNs was composed of polyvinyl pyrrolidone (PVP) K90 as the tip, the photopolymerized PVP as the base and the drug, which owned high mechanical strength, leading to easily piecing the skin on the neck and high drug release in vivo. The cinnarizine MNs markedly improved the recovery of spatial memory and spontaneous exploratory behavior of the rats after microwave radiation by inhibiting the expression of calcineurin and calpain-1. The dissolving MN technique is a promising method to improve drugs into the body and perform the anti-microwave radiation action.
研究领域:
药理学
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神经科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2023
·
IF 7.4
Yuan Hu,Miao Zhang,Bihan Liu,Yingying Tang,Zhuo Wang,Tao Wang,Jiaxin Zheng,Junjian Zhang
Alzheimer's Dementia (AD) and Vascular Dementia (VaD) are two main types of dementias for which no specific treatment is available. Chronic Cerebral Hypoperfusion (CCH) is a pathogenesis underlying AD and VaD that promotes neuroinflammatory responses and oxidative stress . Honokiol (HNK) is a natural compound isolated from magnolia leaves that can easily cross blood brain barrier and has anti-inflammatory and antioxidant effects. In the present study, the effects of HNK on astrocyte polarization and neurological damage in in vivo and in vitro models of chronic cerebral hypoperfusion were explored. We found that HNK was able to inhibit the phosphorylation and nuclear translocation of STAT3 , A1 polarization, and reduce conditioned medium's neuronal toxicity of astrocyte under chronic hypoxia induced by cobalt chloride ; STAT3 phosphorylation inhibitor C188-9 was able to mimic the above effects of HNK, suggesting that HNK may inhibit chronic hypoxia-induced A1 polarization in astrocytes via STAT3. SIRT3 inhibitor 3-TYP reversed, while Sirt3 overexpression mimicked the inhibitory effects of HNK on oxidative stress, STAT3 phosphorylation and nuclear translocation, A1 polarization and neuronal toxicity of astrocyte under chronic hypoxic conditions. For in vivo research, continuous intraperitoneal injection of HNK (1 mg/kg) for 21 days ameliorated the decrease in SIRT3 activity and oxidative stress, inhibited astrocytic STAT3 nuclear translocation and A1 polarization, and prevented neuron and synaptic loss in the hippocampal of CCH rats. Besides, HNK application improved the spatial memory impairment of CCH rats, as assessed with Morris Water Maze . In conclusion, these results suggest that the phytochemical HNK can inhibit astrocyte A1 polarization via regulating SIRT3-STAT3 axis, thus improving CCH-induced neurological damage. These results highlight HNK as novel treatment for dementia with underlying vascular mechanisms.
研究领域:
神经科学
·
药理学
·
神经退行性疾病
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分子生物学
·
植物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2019
·
IF 6.054
Xiaodong Dou,Huixia Huang,Yibo Li,Lan Jiang,Yanxing Wang,Hongwei Jin,Ning Jiao,Lihe Zhang,Liangren Zhang,Zhenming Liu
Alzheimer’s disease (AD) is one of the most challenging diseases around the world with no effective clinical treatment. Previous studies have suggested c-Jun N-terminal kinase 3 (JNK3) as an attractive therapeutic target for AD. Herein, we report 3-substituted indolin-2-one derivatives as the first isoform-selective JNK3 inhibitors by multistage screening. In this study, comparative structure-based virtual screening was performed, and J30-8 was identified with a half-maximal inhibitory concentration of 40 nM, which exhibited over 2500-fold isoform selectivity and marked kinome-wide selectivity. Further study indicated that 1 μM J30-8 exhibited neuroprotective activity in vitro so as to alleviate the spatial memory impairment in vivo through reducing plaque burden and inhibiting the phosphorylation of JNKs, Aβ precursor protein, and Tau protein. All of these indicated J30-8 as proved isoform-selective JNK3 inhibitors that might serve as a useful tool for further JNK3 studies with AD as well as for the development of JNK3 inhibitors for the potential treatment of neurodegenerative diseases.
研究领域:
神经科学
·
药理学
·
药物发现
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Wenqin Yang,Yulong Shi,Yiwei Zhang,Yating Yang,Yufan Du,Zixiao Yang,Xiaorong Wang,Ting Lei,Yanyan Xu,Yongke Chen,Fan Tong,Yazhen Wang,Qianqian Huang,Chuan Hu,Huile Gao
The unsatisfactory treatment outcome of Alzheimer’s disease (AD) can be attributed to two primary factors, the intricate pathogenic mechanisms leading to restricted treatment effectiveness against single targets and the hindered drug accumulation in brain due to blood–brain barrier obstruction. Therefore, we developed a carrier-free nanomodulator (NanoDS) through the self-assembly of donepezil and simvastatin for direct nose-to-brain delivery. This approach facilitated a rapid and efficient traversal through the nasal epithelial barrier, enabling subsequent drug release and achieving multiple therapeutic effects. Among them, donepezil effectively ameliorated the symptoms of AD and restored synaptic plasticity. Simvastatin exerted a neurotrophic effect and facilitated the clearance of amyloid-β aggregation. At the same time, NanoDS demonstrated effective anti-inflammatory and antioxidative stress effects. This therapy for AD is approached from both symptomatic and etiological perspectives. In the treatment of FAD4T transgenic mice, it highly improved spatial memory impairment and cognitive deficits while restoring the homeostasis of brain microenvironment. Collectively, our study presented a paradigm for both achieving efficient brain delivery and offering pleiotropic therapies for AD.
研究领域:
神经科学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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