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胚胎期酒精暴露会改变成年斑马鱼的胆碱能神经递质传递和记忆。

Embryonic alcohol exposure alters cholinergic neurotransmission and memory in adult zebrafish.

机构信息

Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil; Department of Physiology and Behavior, Federal University of Rio Grande do Norte, Natal, RN 59072-970, Brazil; Graduate Program in Psychobiology, Biosciences Center, Federal University of Rio Grande do Norte, Natal, RN 59072-970, Brazil; Laboratory of Experimental Neuropsychobiology, Department of Biochemistry and Molecular Biology, Natural and Exact Sciences Center, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil; Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil.

Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.

出版信息

Behav Brain Res. 2024 Oct 2;474:115176. doi: 10.1016/j.bbr.2024.115176. Epub 2024 Aug 2.

DOI:10.1016/j.bbr.2024.115176
PMID:39098400
Abstract

Alcohol is the most consumed addictive substance worldwide that elicits multiple health problems. Consumption of alcoholic beverages by pregnant women is of great concern because pre-natal exposure can trigger fetal alcohol spectrum disorder (FASD). This disorder can significantly change the embryo's normal development, mainly by affecting the central nervous system (CNS), leading to neurobehavioral consequences that persist until adulthood. Among the harmful effects of FASD, the most reported consequences are cognitive and behavioral impairments. Alcohol interferes with multiple pathways in the brain, affecting memory by impairing neurotransmitter systems, increasing the rate of oxidative stress, or even activating neuroinflammation. Here, we aimed to evaluate the deleterious effects of alcohol on the cholinergic signaling and memory in a FASD zebrafish model, using inhibitory avoidance and novel object recognition tests. Four months after the embryonic exposure to ethanol, the behavioral tests indicated that ethanol impairs memory. While both ethanol concentrations tested (0.5 % and 1 %) disrupted memory acquisition in the inhibitory avoidance test, 1 % ethanol impaired memory in the object recognition test. Regarding the cholinergic system, 0.5 % ethanol decreased ChAT and AChE activities, but the relative gene expression did not change. Overall, we demonstrated that FASD model in zebrafish impairs memory in adult individuals, corroborating the memory impairment associated with embryonic exposure to ethanol. In addition, the cholinergic system was also affected, possibly showing a relation with the cognitive impairment observed.

摘要

酒精是全球范围内最常被滥用的物质,会引发多种健康问题。孕妇饮酒是一个非常值得关注的问题,因为产前暴露会引发胎儿酒精谱系障碍(FASD)。这种疾病会极大地改变胚胎的正常发育,主要通过影响中枢神经系统(CNS),导致持续到成年的神经行为后果。在 FASD 的有害影响中,报道最多的后果是认知和行为障碍。酒精会干扰大脑中的多个途径,通过损害神经递质系统、增加氧化应激速率,甚至激活神经炎症来影响记忆。在这里,我们旨在使用抑制性回避和新物体识别测试,评估酒精对 FASD 斑马鱼模型中的胆碱能信号和记忆的有害影响。胚胎暴露于乙醇 4 个月后,行为测试表明乙醇会损害记忆。虽然测试的两种乙醇浓度(0.5%和 1%)都破坏了抑制性回避测试中的记忆获得,但 1%乙醇破坏了物体识别测试中的记忆。关于胆碱能系统,0.5%乙醇降低了 ChAT 和 AChE 的活性,但相对基因表达没有改变。总的来说,我们证明了斑马鱼的 FASD 模型会损害成年个体的记忆,这与胚胎暴露于乙醇导致的记忆损伤相一致。此外,胆碱能系统也受到了影响,这可能与观察到的认知障碍有关。

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