Oliveira Ana Ca, Pereira Maria Cs, Santana Luana N da Silva, Fernandes Rafael M, Teixeira Francisco B, Oliveira Gedeão B, Fernandes Luanna Mp, Fontes-Júnior Enéas A, Prediger Rui D, Crespo-López Maria E, Gomes-Leal Walace, Lima Rafael R, Maia Cristiane do Socorro Ferraz
Laboratory of Functional and Structural Biology, Federal University of Pará, Belém-Pará, Brazil Laboratory of Experimental Neuroprotection and Neuroregeneration, Federal University of Pará, Belém-Pará, Brazil.
Laboratory of Pharmacology of Inflammation and Behavior, Federal University of Pará, Belém-Pará, Brazil.
J Psychopharmacol. 2015 Jun;29(6):712-24. doi: 10.1177/0269881115581960. Epub 2015 Apr 28.
There is increasing evidence that heavy ethanol exposure in early life may produce long-lasting neurobehavioral consequences, since brain structural maturation continues until adolescence. It is well established that females are more susceptible to alcohol-induced neurotoxicity and that ethanol consumption is increasing among women, especially during adolescence. In the present study, we investigated whether chronic ethanol exposure during adolescence through early adulthood in female rats may induce hippocampal histological damage and neurobehavioral impairments. Female rats were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) by gavage from the 35(th)-90(th) day of life. Ethanol-exposed animals displayed reduced exploration of the central area and increased number of fecal boluses in the open field test indicative of anxiogenic responses. Moreover, chronic high ethanol exposure during adolescence induced marked impairments on short-term memory of female rats addressed on social recognition and step-down inhibitory avoidance tasks. These neurobehavioral deficits induced by ethanol exposure during adolescence through early adulthood were accompanied by the reduction of hippocampal formation volume as well as the loss of neurons, astrocytes and microglia cells in the hippocampus. These results indicate that chronic high ethanol exposure during adolescence through early adulthood in female rats induces long-lasting emotional and memory deficits associated with morphological and molecular alterations in the hippocampus.
越来越多的证据表明,由于大脑结构成熟会持续到青春期,早年大量接触乙醇可能会产生长期的神经行为后果。众所周知,女性更容易受到酒精诱导的神经毒性影响,而且女性的乙醇消费量正在增加,尤其是在青春期。在本研究中,我们调查了雌性大鼠从青春期到成年早期长期接触乙醇是否会导致海马组织学损伤和神经行为障碍。从出生第35天到第90天,通过灌胃法给雌性大鼠喂食蒸馏水或乙醇(6.5克/千克/天,22.5%重量/体积)。在旷场试验中,接触乙醇的动物对中央区域的探索减少,粪便团块数量增加,这表明有焦虑反应。此外,青春期长期高剂量接触乙醇会导致雌性大鼠在社会识别和阶梯式抑制回避任务中的短期记忆出现明显障碍。青春期到成年早期接触乙醇所诱发的这些神经行为缺陷伴随着海马结构体积的减小以及海马中神经元、星形胶质细胞和小胶质细胞的丢失。这些结果表明,雌性大鼠从青春期到成年早期长期高剂量接触乙醇会导致与海马形态和分子改变相关的长期情绪和记忆缺陷。