CELL BIOCHEMISTRY AND BIOPHYSICS
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2014
·Vol. 71
·期 1
·345-351
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IF 2.38
Feng Tianda,Liu Yunhui,Li Chao,Li Zhen
The goal of this study was to assess the expression of poly ADP-ribose polymerase (PARP) and apoptosis-inducing factor (AIF) in the hippocampal CA1 region, and to find out whether nigranoic acid treatment exhibits protective effects on brain through PARP/AIF signaling pathway in cerebral ischemia–reperfusion animal model. Rats were randomly divided into three groups: Sham-surgery, ischemia–reperfusion, and nigranoic acid-treated. Rat models of middle cerebral artery occlusion were prepared using a way of thread occlusion. Rats in the nigranoic acid group were administered with 1 mg/kg intragastric nigranoic acid 6 and 2 h before brain ischemia, respectively. Following reperfusion, samples were collected at different time-points (6, 24, and 72 h) and each group was further divided into three subgroups. Apoptosis was measured using the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling method. The protein expression levels of AIF and PARP were detected using Western blot and AIF mRNA quantity was evaluated using the reverse transcription-polymerase chain reaction. Apoptosis, levels of AIF and PARP protein expression, and levels of AIF mRNA expression were significantly increased in the ischemia–reperfusion group compared with the sham-surgery group. However, apoptosis and the expression levels of AIF protein, PARP protein, and AIF mRNA at different time-points were significantly decreased in the nigranoic acid-treated group compared with the model group. We can judge that nigranoic acid has a strong protective effect on rat cerebral ischemia–reperfusion injury, and acts by downregulating nerve cell apoptosis by preventing the overactivation of PARP and AIF nuclear translocation.
研究领域:
神经科学
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药理学
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分子生物学
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PubMed
高影响因子
Advanced Science
·
2024
·Vol. 11
·期 29
·2401670
·
IF 14.3
Shiya Lv,Fan Mo,Zhaojie Xu,Yu Wang,Gucheng Yang,Meiqi Han,Luyi Jing,Wei Xu,Yiming Duan,Yaoyao Liu,Ming Li,Juntao Liu,Jinping Luo,Mixia Wang,Yilin Song,Yirong Wu,Xinxia Cai
Hippocampal CA1 neurons show intense firing at specific spatial locations, modulated by isolated landmarks. However, the impact of real-world scene transitions on neuronal activity remains unclear. Moreover, long-term neural recording during movement challenges device stability. Conventional rigid-based electrodes cause inflammatory responses, restricting recording durations. Inspired by the jellyfish tentacles, the multi-conductive layer ultra-flexible microelectrode arrays (MEAs) are developed. The tentacle MEAs ensure stable recordings during movement, thereby enabling the discovery of soft boundary neurons. The soft boundary neurons demonstrate high-frequency firing that aligns with the boundaries of scene transitions. Furthermore, the localization ability of soft boundary neurons improves with more scene transition boundaries, and their activity decreases when these boundaries are removed. The innovation of ultra-flexible, high-biocompatible tentacle MEAs improves the understanding of neural encoding in spatial cognition. They offer the potential for long-term in vivo recording of neural information, facilitating breakthroughs in the understanding and application of brain spatial navigation mehanisms.
研究领域:
神经科学
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生物医学工程
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PubMed
高影响因子
Aging-US
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2019
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IF 5.515
Jin-Lan Huang,Chao Yu,Min Su,Si-Man Yang,Fan Zhang,Yuan-Yuan Chen,Jin-Yuan Liu,Yi-Fan Jiang,Zhen-Guo Zhong,Deng-Pan Wu
Oxidative stress plays a vital role in the initiation and progression of age-related neurodegenerative diseases. Ameliorating oxidative damage is therefore considered as a beneficial strategy for the treatment of age-related neurodegenerative disorders. Probucol (Prob), a lipid-lowering prototype agent, was reported to treat cardiovascular diseases, chronic kidney disease and diabetes mellitus. However, whether Prob has an effect on age-related neurodegenerative diseases remains unknown. In the study, it was found that Prob ameliorated D-galactose (D-gal) induced cognitive deficits and neuronal loss in the hippocampal CA1 region. Moreover, Prob alleviated ROS and MDA levels by elevating SOD, GSH-PX and HO-1 mRNA and protein expressions, and improving plasmic and cerebral SOD and GSH-PX activities in D-gal treated mice. Furthermore, Prob promoted the dissociation of Keap1/Nrf2 complex leading to the accumulation of Nrf2 in nucleus, implying that the improved anti-oxidant property of Prob is mediated by Keap1/Nrf2 pathway. The study firstly demonstrates the favorable effects of Prob against cognitive impairments in a senescent mouse model, rendering this compound a promising agent for the treatment or prevention of age-related neurodegenerative disease.
研究领域:
神经科学
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药理学
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衰老研究
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
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2024
·
IF 6.8
Chang Di,Tong Wu,Kai Gao,Na Li,Huifang Song,Lili Wang,Haojie Sun,Jingyun Yi,Xinran Zhang,Jiexin Chen,Mala Shah,Yuwu Jiang,Zhuo Huang
Background and Purpose KCNT1 encodes a sodium-activated potassium channel (Slack channel), and its mutation can cause several forms of epilepsy. Traditional antiepileptic medications have limited efficacy in treating patients with KCNT1 mutations. Here, we describe one heterozygous KCNT1 mutation, M267T, in a patient with EIMFS. The pathological channel properties of this mutation and its effect on neuronal excitability were investigated. Additionally, this study aimed to develop a medication for effective prevention of KCNT1 mutation-induced seizures. Experimental Approach Wild-type or mutant KCNT1 plasmids were expressed heterologously in Xenopus laevis oocytes, and channel property assessment and drug screening were performed based on two-electrode voltage-clamp recordings. The single-channel properties were investigated using the excised inside-out patches from HEK293T cells. Through in utero electroporation, WT and M267T Slack channels were expressed in the hippocampal CA1 pyramidal neurons in male mice, followed by the examination of the electrical properties using the whole-cell current-clamp technique. The kainic acid-induced epilepsy model in male mice was used to evalute the antiseizure effects of carvedilol. Key Results The KCNT1 M267T mutation enhanced Slack channel function by increasing single-channel open probability. Through screening 16 FDA-approved ion channel blockers, we found that carvedilol effectively reversed the mutation-induced gain-of-function channel properties. Notably, the KCNT1 M267T mutation in the mouse hippocampal CA1 pyramidal neurons affected afterhyperpolarization properties and induced neuronal hyperexcitability, which was inhibited by carvedilol. Additionally, carvedilol exhibited antiseizure effects in the kainic acid-induced epilepsy model. Conclusion and Implication Our findings suggest carvedilol as a new potential candidate for treatment of epilepsies. Graphical
研究领域:
神经科学
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药理学
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分子生物学
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医学遗传学
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DOI
PubMed
高影响因子
BEHAVIOURAL BRAIN RESEARCH
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2020
·
IF 2.977
Yuan-Jian Song,Yue Shi,Miao-Miao Cui,Man Li,Xiang-Ru Wen,Xiao-Yan Zhou,He-Qing Lou,Yu-Lan Wang,Da-Shi Qi,Man Tang,Xun-Bao Zhang
Cerebral ischemia/reperfusion (I/R) injury is a leading cause of learning and memory dysfunction. Hydrogen sulfide (H 2 S) has been shown to confer neuroprotection in various neurodegenerative diseases, including cerebral I/R-induced hippocampal CA1 injury. However, the underlying mechanisms have not been completely understood. In the present study, rats were pretreated with SAM/NaHS (SAM, an H 2 S agonist, and NaHS, an H 2 S donor) only or SAM/NaHS combined with CaM (an activator of CaMKII) prior to cerebral ischemia. The Morris water maze test demonstrated that SAM/NaHS could alleviate learning and memory impairment induced by cerebral I/R injury. Cresyl violet staining was used to show the survival of hippocampal CA1 pyramidal neurons. SAM/NaHS significantly increased the number of surviving cells, whereas CaM weakened the protection induced by SAM/NaHS. The immunohistochemistry results indicated that the number of Iba1-positive microglia significantly increased after cerebral I/R. Compared with the I/R group, the number of Iba1-positive microglia in the SAM/NaHS groups significantly decreased. Co-Immunoprecipitation and immunoblotting were conducted to demonstrate that SAM/NaHS suppressed the assembly of CaMKII with the ASK1-MKK3-p38 signal module after cerebral I/R, which decreased the phosphorylation of p38. In contrast, CaM significantly inhibited the effects of SAM/NaHS. Taken together, the results suggested that SAM/NaHS could suppress cerebral I/R injury by downregulating p38 phosphorylation via decreasing the assembly of CaMKII with the ASK1-MKK3-p38 signal module.
研究领域:
神经科学
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药理学
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神经保护
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信号转导
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DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
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2024
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IF 14.7
Ruizhe Nie,Xinting Zhou,Jiaru Fu,Shanshan Hu,Qilu Zhang,Weikai Jiang,Yizi Yan,Xian Cao,Danhua Yuan,Yan Long,Hao Hong,Susu Tang
Anxiety disorders are one of the most epidemic and chronic psychiatric disorders. An incomplete understanding of anxiety pathophysiology has limited the development of highly effective drugs against these disorders. GPR17 has been shown to be involved in multiple sclerosis and some acute brain injury disorders. However, no study has investigated the role of GPR17 in psychiatric disorders. In a well-established chronic restraint stress (CRS) mouse model, using a combination of pharmacological and molecular biology techniques, viral tracing, in vitro electrophysiology recordings, in vivo fiber photometry, chemogenetic manipulations and behavioral tests, we demonstrated that CRS induced anxiety-like behaviors and increased the expression of GPR17 in basolateral amygdala (BLA) glutamatergic neurons. Inhibition of GPR17 by cangrelor or knockdown of GPR17 by adeno-associated virus in BLA glutamatergic neurons effectively improved anxiety-like behaviors. Overexpression of GPR17 in BLA glutamatergic neurons increased the susceptibility to anxiety-like behaviors. What's more, BLA glutamatergic neuronal activity was required for anxiolytic-like effects of GPR17 antagonist and GPR17 modulated anxiety-like behaviors via BLA to ventral hippocampal CA1 glutamatergic projection. Our study finds for the first and highlights the new role of GPR17 in regulating anxiety-like behaviors and it might be a novel potential target for therapy of anxiety disorders.
研究领域:
神经科学
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药理学
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分子生物学
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行为科学
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PubMed
高影响因子
CELL
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2022
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IF 66.85
Shu-Hsien Sheu,Srigokul Upadhyayula,Vincent Dupuy,Song Pang,Fei Deng,Jinxia Wan,Deepika Walpita,H. Amalia Pasolli,Justin Houser,Silvia Sanchez-Martinez,Sebastian E. Brauchi,Sambashiva Banala,Melanie Freeman,C. Shan Xu,Tom Kirchhausen,Harald F. Hess,Luke Lavis,Yulong Li,Séverine Chaumont-Dubel,David E. Clapham
Summary Chemical synapses between axons and dendrites mediate neuronal intercellular communication. Here, we describe a synapse between axons and primary cilia: the axo-ciliary synapse. Using enhanced focused ion beam-scanning electron microscopy on samples with optimally preserved ultrastructure, we discovered synapses between brainstem serotonergic axons and the primary cilia of hippocampal CA1 pyramidal neurons. Functionally, these cilia are enriched in a ciliary-restricted serotonin receptor, the 5-hydroxytryptamine receptor 6 (5-HTR6). Using a cilia-targeted serotonin sensor, we show that opto- and chemogenetic stimulation of serotonergic axons releases serotonin onto cilia. Ciliary 5-HTR6 stimulation activates a non-canonical G αq/11 -RhoA pathway, which modulates nuclear actin and increases histone acetylation and chromatin accessibility. Ablation of this pathway reduces chromatin accessibility in CA1 pyramidal neurons. As a signaling apparatus with proximity to the nucleus, axo-ciliary synapses short circuit neurotransmission to alter the postsynaptic neuron’s epigenetic state.
研究领域:
神经科学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2021
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IF 11.614
Lulu Pang,Siqing Zhu,Jinqiu Ma,Lin Zhu,Yijing Liu,Ge Ou,Ruiteng Li,Yaxin Wang,Yi Liang,Xu Jin,Lina Du,Yiguang Jin
Post-traumatic stress disorder (PTSD) is a psychiatric disease that seriously affects brain function. Currently, selective serotonin reuptake inhibitors (SSRIs) are used to treat PTSD clinically but have decreased efficiency and increased side effects. In this study, nasal cannabidiol inclusion complex temperature-sensitive hydrogels (CBD TSGs) were prepared and evaluated to treat PTSD. Mice model of PTSD was established with conditional fear box. CBD TSGs could significantly improve the spontaneous behavior, exploratory spirit and alleviate tension in open field box, relieve anxiety and tension in elevated plus maze, and reduce the freezing time. Hematoxylin and eosin and c-FOS immunohistochemistry slides showed that the main injured brain areas in PTSD were the prefrontal cortex, amygdala, and hippocampus CA1. CBD TSGs could reduce the level of tumor necrosis factor- α caused by PTSD. Western blot analysis showed that CBD TSGs increased the expression of the 5-HT1A receptor. Intranasal administration of CBD TSGs was more efficient and had more obvious brain targeting effects than oral administration, as evidenced by the pharmacokinetics and brain tissue distribution of CBD TSGs. Overall, nasal CBD TSGs are safe and effective and have controlled release. There are a novel promising option for the clinical treatment of PTSD.
研究领域:
药学
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神经科学
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精神病学
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药物递送系统
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DOI
PubMed
高影响因子
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