青少年间歇性接触乙醇期间和之后前额叶皮层和磁细胞基底核神经营养素表达的失调

IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Brian T. Kipp, Polliana T. Nunes, Lisa M. Savage
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引用次数: 0

摘要

青少年间歇性乙醇暴露(AIE)是人类青少年暴饮暴食的临床前模型,它再现了青少年大量暴饮暴食的消费模式,并确定基底前脑胆碱能神经元的缺失是该模型的病理特征。支配前额叶皮层(PFC)的基底大细胞核(NbM)胆碱能神经元特别容易受到酒精相关神经变性的影响。目标神经营养素(神经生长因子 [NGF] 和脑源性神经营养因子 [BDNF])可调节胆碱能表型的表达和存活。来自其他疾病模型的证据表明,未成熟神经营养素(或称前神经营养素)在神经营养受体上的活性在促进胆碱能变性方面起着重要作用;但这一作用在青少年暴饮暴食中尚未得到探讨。我们试图在 AIE 模型中描述前神经营养素和成熟神经营养素的表达,以及它们的同源受体和胆碱能标记物。雄性和雌性 Sprague Dawley 大鼠从出生后第 25-57 天开始,以两天为周期,每公斤灌胃 5 克 20% EtOH 或水。大鼠在最后一次灌胃后 2 小时、24 小时或 3 周后被处死,并收集组织进行蛋白质测定。Western印迹分析表明,乙醇中毒降低了PFC中BDNF和囊泡乙酰胆碱转运体(vAChT)的表达,而AIE处理的动物NbM中NGF的表达较低。在急性酒精戒断期间,PFC中的proNGF增加而proBDNF减少,NbM中的proBDNF增加而NGF减少。在AIE戒断期间,PFC中神经营养素、其受体和vAChT的表达与对照组没有差异。相反,在NbM中,AIE后NGF和胆碱乙酰转移酶(ChAT)的表达长期减少。总之,这些研究结果表明,在中毒和戒断期间,AIE会改变前神经营养素和神经营养素的表达,通过增加前NGF和前BDNF的表达,同时减少NGF和BDNF的表达,从而有利于促进退行性机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dysregulation of neurotrophin expression in prefrontal cortex and nucleus basalis magnocellularis during and after adolescent intermittent ethanol exposure

A preclinical model of human adolescent binge drinking, adolescent intermittent ethanol exposure (AIE) recreates the heavy binge withdrawal consummatory patterns of adolescents and has identified the loss of basal forebrain cholinergic neurons as a pathological hallmark of this model. Cholinergic neurons of the nucleus basalis magnocellularis (NbM) that innervate the prefrontal cortex (PFC) are particularly vulnerable to alcohol related neurodegeneration. Target derived neurotrophins (nerve growth factor [NGF] and brain-derived neurotrophic factor [BDNF]) regulate cholinergic phenotype expression and survival. Evidence from other disease models implicates the role of immature neurotrophin, or proneurotrophins, activity at neurotrophic receptors in promoting cholinergic degeneration; however, it has yet to be explored in adolescent binge drinking. We sought to characterize the pro- and mature neurotrophin expression, alongside their cognate receptors and cholinergic markers in an AIE model. Male and female Sprague Dawley rats underwent 5 g/kg 20% EtOH or water gavage on two-day-on, two-day-off cycles from post-natal day 25–57. Rats were sacrificed 2 h, 24 h, or 3 weeks following the last gavage, and tissue were collected for protein measurement. Western blot analyses revealed that ethanol intoxication reduced the expression of BDNF and vesicular acetylcholine transporter (vAChT) in the PFC, while NGF was lower in the NbM of AIE treated animals. During acute alcohol withdrawal, proNGF in the PFC was increased while proBDNF decreased, and in the NbM proBDNF increased while NGF decreased. During AIE abstinence, the expression of neurotrophins, their receptors, and vAChT did not differ from controls in the PFC. In contrast, in the NbM the expression of both NGF and choline acetyltransferase (ChAT) were reduced long-term following AIE. Taken together these findings suggest that AIE alters the expression of proneurotrophins and neurotrophins during intoxication and withdrawal that favor prodegenerative mechanisms by increasing the expression of proNGF and proBDNF, while also reducing NGF and BDNF.

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来源期刊
Alcohol
Alcohol 医学-毒理学
CiteScore
4.60
自引率
4.30%
发文量
74
审稿时长
15.6 weeks
期刊介绍: Alcohol is an international, peer-reviewed journal that is devoted to publishing multi-disciplinary biomedical research on all aspects of the actions or effects of alcohol on the nervous system or on other organ systems. Emphasis is given to studies into the causes and consequences of alcohol abuse and alcoholism, and biomedical aspects of diagnosis, etiology, treatment or prevention of alcohol-related health effects. Intended for both research scientists and practicing clinicians, the journal publishes original research on the neurobiological, neurobehavioral, and pathophysiological processes associated with alcohol drinking, alcohol abuse, alcohol-seeking behavior, tolerance, dependence, withdrawal, protracted abstinence, and relapse. In addition, the journal reports studies on the effects alcohol on brain mechanisms of neuroplasticity over the life span, biological factors associated with adolescent alcohol abuse, pharmacotherapeutic strategies in the treatment of alcoholism, biological and biochemical markers of alcohol abuse and alcoholism, pathological effects of uncontrolled drinking, biomedical and molecular factors in the effects on liver, immune system, and other organ systems, and biomedical aspects of fetal alcohol spectrum disorder including mechanisms of damage, diagnosis and early detection, treatment, and prevention. Articles are published from all levels of biomedical inquiry, including the following: molecular and cellular studies of alcohol''s actions in vitro and in vivo; animal model studies of genetic, pharmacological, behavioral, developmental or pathophysiological aspects of alcohol; human studies of genetic, behavioral, cognitive, neuroimaging, or pathological aspects of alcohol drinking; clinical studies of diagnosis (including dual diagnosis), treatment, prevention, and epidemiology. The journal will publish 9 issues per year; the accepted abbreviation for Alcohol for bibliographic citation is Alcohol.
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