Neurochemistry international最新文献_第10页

DARPP-32/protein phosphatase 1 regulates Rasgrp2 as a novel component of dopamine D1 receptor signaling in striatum DARPP-32/蛋白磷酸酶1作为纹状体多巴胺D1受体信号传导的新组分调控Rasgrp2

IF 4.2 3区医学

Neurochemistry international Pub Date : 2023-01-01 DOI: 10.1016/j.neuint.2022.105438

Mahomi Kuroiwa , Takahide Shuto , Taku Nagai , Mutsuki Amano , Kozo Kaibuchi , Angus C. Nairn , Akinori Nishi

{"title":"DARPP-32/protein phosphatase 1 regulates Rasgrp2 as a novel component of dopamine D1 receptor signaling in striatum","authors":"Mahomi Kuroiwa , Takahide Shuto , Taku Nagai , Mutsuki Amano , Kozo Kaibuchi , Angus C. Nairn , Akinori Nishi","doi":"10.1016/j.neuint.2022.105438","DOIUrl":"10.1016/j.neuint.2022.105438","url":null,"abstract":"<div>Dopamine regulates psychomotor function by D1 receptor/PKA-dependent phosphorylation of DARPP-32. DARPP-32, phosphorylated at Thr34 by PKA, inhibits protein phosphatase 1 (PP1), and amplifies the phosphorylation of other PKA/PP1 substrates following D1 receptor activation. In addition to the D1 receptor/PKA/DARPP-32 signaling pathway, D1 receptor stimulation is known to activate Rap1/ERK signaling. Rap1 activation is mediated through the phosphorylation of Rasgrp2 (guanine nucleotide exchange factor; activation) and Rap1gap (GTPase-activating protein; inhibition) by PKA. In this study, we investigated the role of PP1 inhibition by phospho-Thr34 DARPP-32 in the D1 receptor-induced phosphorylation of Rasgrp2 and Rap1gap at PKA sites. The analyses in striatal and NAc slices from wild-type and DARPP-32 knockout mice revealed that the phosphorylation of Rasgrp2 at Ser116/Ser117 and Ser586, but not of Rasgrp2 at Ser554 or Rap1gap at Ser441 or Ser499 induced by a D1 receptor agonist, is under the control of the DARPP-32/PP1. The results were supported by pharmacological analyses using a selective PP1 inhibitor, tautomycetin. In addition, analyses using a PP1 and PP2A inhibitor, okadaic acid, revealed that all sites of Rasgrp2 and Rap1gap were regulated by PP2A. Thus, the interactive machinery of DARPP-32/PP1 may contribute to efficient D1 receptor signaling via Rasgrp2/Rap1 in the striatum.</div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"162 ","pages":"Article 105438"},"PeriodicalIF":4.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10686927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Trimethylamine N-oxide aggravated cognitive impairment from APP/PS1 mice and protective roles of voluntary exercise 三甲胺n -氧化物加重APP/PS1小鼠认知功能障碍及自主运动的保护作用

IF 4.2 3区医学

Neurochemistry international Pub Date : 2023-01-01 DOI: 10.1016/j.neuint.2022.105459

Ying Zhang , Guiping Wang , Rui Li , Ruitong Liu , Zengli Yu , Zengli Zhang , Zhongxiao Wan

{"title":"Trimethylamine N-oxide aggravated cognitive impairment from APP/PS1 mice and protective roles of voluntary exercise","authors":"Ying Zhang , Guiping Wang , Rui Li , Ruitong Liu , Zengli Yu , Zengli Zhang , Zhongxiao Wan","doi":"10.1016/j.neuint.2022.105459","DOIUrl":"10.1016/j.neuint.2022.105459","url":null,"abstract":"<div>To determine whether trimethylamine N-oxide (TMAO) would aggravate cognitive dysfunction from APP/PS1 mice and the potential protective effects of voluntary wheel running (VWR). TMAO impaired learning and memory abilities, and exercise reversed TMAO induced cognitive impairment. Serum TMAO, choline, betaine and TMA were significantly elevated from TMAO group, while exercise group had decreased TMAO, betaine and TMA level. TMAO group has significantly upregulated BACE1 from both hippocampus and cortex, also increased cathepsin B, p-Tau at Ser396&Ser404, GFAP, p-NF-κB p65 in cortex, while reduced BDNF, synaptophysin and PSD95 in hippocampus, also reduced occludin and ZO-1 from cortex, and reduced occludin from colon. In contrast, BACE1 from both hippocampus and cortex, also cathepsin B and p-Tauser396 from cortex were reduced, BDNF, snaptophysin, and PSD95 from hippocampus, ZO-1 from cortex, and occludin from colon were elevated post exercise compared to TMAO group. Exercise elevated α diversity index of cecal content, and TMAO and exercise affected gut microbiota profiles differentially. In conclusion, TMAO led to gut microbiota dysbiosis, impaired gut-brain integrity, elevated neuroinflammation, Aβ pathology and tau phosphorylation, disordered synaptic function; and exercise could reverse TMAO induced cognitive dysfunction via improving the above markers. The potential deleterious effects of TMAO on cognitive function need to be validated in humans, also dosages of exercise for exerting neuroprotective effects against TMAO induced cognitive impairment.</div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"162 ","pages":"Article 105459"},"PeriodicalIF":4.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10695401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 1

Efficacy of novel SPAK inhibitor ZT-1a derivatives (1c, 1d, 1g & 1h) on improving post-stroke neurological outcome and brain lesion in mice 新型SPAK抑制剂ZT-1a衍生物(1c, 1d, 1g和1h)对小鼠脑卒中后神经预后和脑损伤的改善作用

IF 4.2 3区医学

Neurochemistry international Pub Date : 2023-01-01 DOI: 10.1016/j.neuint.2022.105441

Mohammad Iqbal H. Bhuiyan , Sydney Fischer , Shivani M. Patel , Helena Oft , Ting Zhang , Lesley M. Foley , Jinwei Zhang , T. Kevin Hitchens , Bradley J. Molyneaux , Xianming Deng , Dandan Sun

{"title":"Efficacy of novel SPAK inhibitor ZT-1a derivatives (1c, 1d, 1g & 1h) on improving post-stroke neurological outcome and brain lesion in mice","authors":"Mohammad Iqbal H. Bhuiyan , Sydney Fischer , Shivani M. Patel , Helena Oft , Ting Zhang , Lesley M. Foley , Jinwei Zhang , T. Kevin Hitchens , Bradley J. Molyneaux , Xianming Deng , Dandan Sun","doi":"10.1016/j.neuint.2022.105441","DOIUrl":"10.1016/j.neuint.2022.105441","url":null,"abstract":"<div>SPAK inhibitor ZT-1a was previously shown to be neuroprotective in murine ischemic stroke models. In this study, we further examined the efficacy of four ZT-1a derivatives (ZT-1c, -1d, -1g and -1h) on reducing stroke-induced sensorimotor function impairment and brain lesions. Vehicle control (Veh) or ZT-1 derivatives were administered via osmotic pump to adult C57BL/6J mice during 3–21 h post-stroke. Neurological behavior of these mice was assessed at days 1, 3, 5, and 7 post-stroke and MRI T2WI and DTI analysis was subsequently conducted in ex vivo brains. Veh-treated stroke mice displayed sensorimotor function deficits compared to Sham mice. In contrast, mice receiving ZT-1a derivatives displayed significantly lower neurological deficits at days 3–7 post-stroke (p < 0.05), with ZT-1a, ZT-1c and ZT-1d showing greater impact than ZT-1h and ZT-1g. ZT-1a treatment was the most effective in reducing brain lesion volume on T2WI and in preserving NeuN + neurons (p < 0.01), followed by ZT-1d > -1c > -1g > -1h. The Veh-treated stroke mice displayed white matter tissue injury, reflected by reduced fractional anisotropy (FA) or axial diffusivity (AD) values in external capsule, internal capsule and hippocampus. In contrast, only ZT-1a-as well as ZT-1c-treated stroke mice exhibited significantly higher FA and AD values. These findings demonstrate that post-stroke administration of SPAK inhibitor ZT-1a and its derivatives (ZT-1c and ZT-1d) is effective in protecting gray and white matter tissues in ischemic brains, showing a potential for ischemic stroke therapy development.</div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"162 ","pages":"Article 105441"},"PeriodicalIF":4.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9258016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 1

The time dimension to stroke: Circadian effects on stroke outcomes and mechanisms 中风的时间维度:昼夜节律对中风结果和机制的影响

IF 4.2 3区医学

Neurochemistry international Pub Date : 2023-01-01 DOI: 10.1016/j.neuint.2022.105457

Pradip K. Kamat , Mohammad Badruzzaman Khan , Cameron Smith , Shahneela Siddiqui , Babak Baban , Krishnan Dhandapani , David C. Hess

{"title":"The time dimension to stroke: Circadian effects on stroke outcomes and mechanisms","authors":"Pradip K. Kamat , Mohammad Badruzzaman Khan , Cameron Smith , Shahneela Siddiqui , Babak Baban , Krishnan Dhandapani , David C. Hess","doi":"10.1016/j.neuint.2022.105457","DOIUrl":"10.1016/j.neuint.2022.105457","url":null,"abstract":"<div>The circadian system is widely involved in the various pathological outcomes affected by time dimension changes. In the brain, the master circadian clock, also known as the “pacemaker,” is present in the hypothalamus's suprachiasmatic nucleus (SCN). The SCN consists of molecular circadian clocks that operate in each neuron and other brain cells. These circadian mechanisms are controlled by the transcription and translation of specific genes such as the clock circadian regulator (Clock) and brain and muscle ARNT-Like 1 (Bmal1). Period (Per1–3) and cryptochrome (Cry1 and 2) negatively feedback and regulate the clock genes. Variations in the circadian cycle and these clock genes can affect stroke outcomes. Studies suggest that the peak stroke occurs in the morning after patients awaken from sleep, while stroke severity and poor outcomes worsen at midnight. The main risk factor associated with stroke is high blood pressure (hypertension). Blood pressure usually dips by 15–20% during sleep, but many hypertensives do not display this normal dipping pattern and are non-dippers. A sleep blood pressure is the primary determinant of stroke risk. This article discusses the possible mechanism associated with circadian rhythm and stroke outcomes.</div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"162 ","pages":"Article 105457"},"PeriodicalIF":4.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9613448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 1

Juvenile social isolation affects the structure of the tanycyte–vascular interface in the hypophyseal portal system of the adult mice 幼年期的社会孤立影响成年小鼠垂体门静脉系统中伸长细胞-血管界面的结构

IF 4.2 3区医学

Neurochemistry international Pub Date : 2023-01-01 DOI: 10.1016/j.neuint.2022.105439

Shoko Takemura , Ayami Isonishi , Noriko Horii-Hayashi , Tatsuhide Tanaka , Kouko Tatsumi , Takashi Komori , Kazuhiko Yamamuro , Mariko Yamano , Mayumi Nishi , Manabu Makinodan , Akio Wanaka

{"title":"Juvenile social isolation affects the structure of the tanycyte–vascular interface in the hypophyseal portal system of the adult mice","authors":"Shoko Takemura , Ayami Isonishi , Noriko Horii-Hayashi , Tatsuhide Tanaka , Kouko Tatsumi , Takashi Komori , Kazuhiko Yamamuro , Mariko Yamano , Mayumi Nishi , Manabu Makinodan , Akio Wanaka","doi":"10.1016/j.neuint.2022.105439","DOIUrl":"10.1016/j.neuint.2022.105439","url":null,"abstract":"<div>Accumulating evidence indicates that social stress in the juvenile period affects hypothalamic–pituitary–adrenal (HPA) axis activity in adulthood. The biological mechanisms underlying this phenomenon remain unclear. We aimed to elucidate them by comparing adult mice that had experienced social isolation from postnatal day 21–35 (juvenile social isolation (JSI) group) with those reared normally (control group). JSI group mice showed an attenuated HPA response to acute swim stress, while the control group had a normal response to this stress. Activity levels of the paraventricular nucleus in both groups were comparable, as shown by c-Fos immunoreactivities and mRNA expression of c-Fos, Corticotropin-releasing factor (CRF), Glucocorticoid receptor, and Mineralocorticoid receptor. We found greater vascular coverage by tanycytic endfeet in the median eminence of the JSI group mice than in that of the control group mice under basal condition and after acute swim stress. Moreover, CRF content after acute swim stress was greater in the median eminence of the JSI group mice than in that of the control group mice. The attenuated HPA response to acute swim stress was specific to JSI group mice, but not to control group mice. Although a direct link awaits further experiments, tanycyte morphological changes in the median eminence could be related to the HPA response.</div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"162 ","pages":"Article 105439"},"PeriodicalIF":4.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10686930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 1

Non-coding RNAs in stroke pathology, diagnostics, and therapeutics 非编码rna在脑卒中病理、诊断和治疗中的应用

IF 4.2 3区医学

Neurochemistry international Pub Date : 2023-01-01 DOI: 10.1016/j.neuint.2022.105467

Nikita Potemkin, Andrew N. Clarkson

{"title":"Non-coding RNAs in stroke pathology, diagnostics, and therapeutics","authors":"Nikita Potemkin, Andrew N. Clarkson","doi":"10.1016/j.neuint.2022.105467","DOIUrl":"10.1016/j.neuint.2022.105467","url":null,"abstract":"<div>Ischemic stroke is a leading cause of death and disability worldwide. Methods to alleviate functional deficits after ischemic stroke focus on restoration of cerebral blood flow to the affected area. However, pharmacological or surgical methods such as thrombolysis and thrombectomy have a narrow effective window. Harnessing and manipulating neurochemical processes of recovery may provide an alternative to these methods. Recently, non-coding RNA (ncRNA) have been increasingly investigated for their contributions to the pathology of diseases and potential for diagnostic and therapeutic applications. Here we will review several ncRNA – H19, MALAT1, ANRIL, NEAT1, pseudogenes, small nucleolar RNA, piwi-interacting RNA and circular RNA – and their involvement in stroke pathology. We also examine these ncRNA as potential diagnostic biomarkers, particularly in circulating blood, and as targets for therapeutic interventions. An important aspect of this is a discussion of potential methods of treatment delivery to allow for targeting of interventions past the blood-brain barrier, including lipid nanoparticles, polymer nanoparticles, and viral and non-viral vectors. Overall, several long non-coding RNA (lncRNA) discussed here have strong implications for the development of pathology and functional recovery after ischemic stroke. LncRNAs H19 and ANRIL show potential as diagnostic biomarkers, while H19 and MALAT1 may prove to be effective therapeutics for both minimising damage as well as promoting recovery. Other ncRNA have also been implicated in ischemic stroke but are currently too poorly understood to make inferences for diagnosis or treatment. Whilst the field of ncRNAs is relatively new, significant work has already highlighted that ncRNAs represent a promising novel investigative tool for understanding stroke pathology, could be used as diagnostic biomarkers, and as targets for therapeutic interventions.</div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"162 ","pages":"Article 105467"},"PeriodicalIF":4.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10686961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Estrogen receptor beta activity contributes to both tumor necrosis factor alpha expression in the hypothalamic paraventricular nucleus and the resistance to hypertension following angiotensin II in female mice 雌激素受体β活性有助于雌性小鼠下丘脑室旁核中肿瘤坏死因子α的表达和血管紧张素II对高血压的抵抗。

IF 4.2 3区医学

Neurochemistry international Pub Date : 2022-12-01 DOI: 10.1016/j.neuint.2022.105420

Clara Woods , Natalina H. Contoreggi , Megan A. Johnson , Teresa A. Milner , Gang Wang , Michael J. Glass

{"title":"Estrogen receptor beta activity contributes to both tumor necrosis factor alpha expression in the hypothalamic paraventricular nucleus and the resistance to hypertension following angiotensin II in female mice","authors":"Clara Woods , Natalina H. Contoreggi , Megan A. Johnson , Teresa A. Milner , Gang Wang , Michael J. Glass","doi":"10.1016/j.neuint.2022.105420","DOIUrl":"10.1016/j.neuint.2022.105420","url":null,"abstract":"<div>Sex differences in the sensitivity to hypertension and inflammatory processes are well characterized but insufficiently understood. In male mice, tumor necrosis factor alpha (TNFα) in the hypothalamic paraventricular nucleus (PVN) contributes to hypertension following slow-pressor angiotensin II (AngII) infusion. However, the role of PVN TNFα in the response to AngII in female mice is unknown. Using a combination of in situ hybridization, high-resolution electron microscopic immunohistochemistry, spatial-temporal gene silencing, and dihydroethidium microfluorography we investigated the influence of AngII on both blood pressure and PVN TNFα signaling in female mice. We found that chronic (14-day) infusion of AngII in female mice did not impact blood pressure, TNFα levels, the expression of the TNFα type 1 receptor (TNFR1), or the subcellular distribution of TNFR1 in the PVN. However, it was shown that blockade of estrogen receptor β (ERβ), a major hypothalamic estrogen receptor, was accompanied by both elevated PVN TNFα and hypertension following AngII. Further, AngII hypertension following ERβ blockade was attenuated by inhibiting PVN TNFα signaling by local TNFR1 silencing. It was also shown that ERβ blockade in isolated PVN-spinal cord projection neurons (i.e. sympathoexcitatory) heightened TNFα-induced production of NADPH oxidase (NOX2)-mediated reactive oxygen species, molecules that may play a key role in mediating the effect of TNFα in hypertension. These results indicate that ERβ contributes to the reduced sensitivity of female mice to hypothalamic inflammatory cytokine signaling and hypertension in response to AngII.</div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"161 ","pages":"Article 105420"},"PeriodicalIF":4.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10415146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

An HPLC-based assay for improved measurement of glutamate decarboxylase inhibition/activation 谷氨酸脱羧酶抑制/激活的高效液相色谱检测方法

IF 4.2 3区医学

Neurochemistry international Pub Date : 2022-12-01 DOI: 10.1016/j.neuint.2022.105433

Marija S. Genčić , Nikola M. Stojanović , Marko Z. Mladenović , Niko S. Radulović

{"title":"An HPLC-based assay for improved measurement of glutamate decarboxylase inhibition/activation","authors":"Marija S. Genčić , Nikola M. Stojanović , Marko Z. Mladenović , Niko S. Radulović","doi":"10.1016/j.neuint.2022.105433","DOIUrl":"10.1016/j.neuint.2022.105433","url":null,"abstract":"<div>L-Glutamic acid decarboxylase (GAD) is an enzyme that ensures the balance between the levels of two neurotransmitters, γ-aminobutyric acid (GABA) and L-glutamic acid (L-Glu), necessary for proper brain functioning. A reduction in the concentrations of GABA and/or GAD activity has been implicated in the symptoms associated with epilepsy, which could be plausibly alleviated by the application of GAD activators. As any unnecessary interference in GAD catalytic activity could be detrimental, it is important to study whether CNS (or other) drug candidates act on GAD or not. The ability to identify and reduce this risk early could significantly improve the process of drug development. Although many methods for measuring GAD activity in various biological samples have been described, only few (such as manometric and radiometric) were adopted as in vitro assays for the screening of potential GAD inhibitors/activators. However, these methods require specialized equipment and/or an expensive radiolabeled substrate, and may have sensitivity and/or reliability issues. Therefore, this study aimed to develop an HPLC-DAD-based assay that would allow a simple and more accurate measurement of GAD inhibition or activation using unpurified mice or rat brain homogenates. This assay is based on the quantification of GABA, formed during the enzymatic reaction, after its derivatization with dansyl chloride. Various parameters were evaluated to optimize the assay procedure (e.g. homogenate volume, incubation time, DMSO content, GAD, GABA, and dansyl-GABA stabilities). This assay was validated for pharmacological screenings using 3-mercaptopropionic acid and gallic acid and GAD obtained from different experimental animals.</div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"161 ","pages":"Article 105433"},"PeriodicalIF":4.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10424596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 2

Social isolation induces succinate dehydrogenase dysfunction in anxious mice 社会隔离诱导焦虑小鼠琥珀酸脱氢酶功能障碍

IF 4.2 3区医学

Neurochemistry international Pub Date : 2022-12-01 DOI: 10.1016/j.neuint.2022.105434

Saki Watanabe , Alzahra J. Al Omran , Amy S. Shao , Zeyu Zhang , Chen Xue , Jifeng Zhang , Junji Watanabe , Jing Liang

引用次数: 0

Verapamil inhibits TXNIP-NLRP3 inflammasome activation and preserves functional recovery after intracerebral hemorrhage in mice 维拉帕米抑制小鼠脑出血后TXNIP-NLRP3炎性小体激活并维持功能恢复

IF 4.2 3区医学

Neurochemistry international Pub Date : 2022-12-01 DOI: 10.1016/j.neuint.2022.105423

Saifudeen Ismael , Devlin Patrick , Mohd. Salman , Arshi Parveen , Ansley Grimes Stanfill , Tauheed Ishrat

{"title":"Verapamil inhibits TXNIP-NLRP3 inflammasome activation and preserves functional recovery after intracerebral hemorrhage in mice","authors":"Saifudeen Ismael , Devlin Patrick , Mohd. Salman , Arshi Parveen , Ansley Grimes Stanfill , Tauheed Ishrat","doi":"10.1016/j.neuint.2022.105423","DOIUrl":"10.1016/j.neuint.2022.105423","url":null,"abstract":"<div>Intracerebral hemorrhage (ICH) is the second most common type of stroke with no satisfactory treatment. Recent studies from our group and others indicated a potential positive effect of verapamil, a commonly prescribed calcium channel blocker, with thioredoxin-interacting protein (TXNIP) inhibitor properties, in ischemic stroke and cognitive disorders. It is unclear whether there would be a beneficial effect of verapamil administration in ICH. Therefore, this study was designed to determine the neuroprotective effects of verapamil in a murine ICH model. ICH was induced by stereotactic injection of collagenase type VII (0.075 U) into the right striatum of adult male C57BL/6 mice. Verapamil (0.15 mg/kg) or saline was administered intravenously at 1 h post-ICH followed by oral (1 mg/kg/d) administration in drinking water for 28 days. Motor and cognitive function were assessed using established tests for motor coordination, spatial learning, short- and long-term memory. A subset of animals was sacrificed at 72 h after ICH for molecular analysis. Verapamil treatment reduced expression of TXNIP and NOD-like receptor pyrin domain-containing-3 inflammasome activation in the perihematomal area. These protective effects of verapamil were associated with decreased proinflammatory mediators, microglial activation, and blood-brain barrier permeability markers and paralleled less phosphorylated nuclear factor kappa B level. Our findings also demonstrate that long-term low-dose verapamil effectively attenuated motor and cognitive impairments. Taken together, these data indicate that verapamil has therapeutic potential in improving acute motor function after ICH. Further investigations are needed to confirm whether verapamil treatment could be a promising candidate for clinical trials.</div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"161 ","pages":"Article 105423"},"PeriodicalIF":4.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10772896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 6