Boschen K E, Criss K J, Palamarchouk V, Roth T L, Klintsova A Y
Department of Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, United States.
Department of Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, United States.
Int J Dev Neurosci. 2015 Jun;43:16-24. doi: 10.1016/j.ijdevneu.2015.03.008. Epub 2015 Mar 21.
Third trimester-equivalent alcohol exposure causes significant deficits in hippocampal and cortical neuroplasticity, resulting in alterations to dendritic arborization, hippocampal adult neurogenesis, and performance on learning tasks. The current study investigated the impact of neonatal alcohol exposure (postnatal days 4-9, 5.25 g/kg/day) on expression of brain-derived neurotrophic factor (BDNF) and the tropomyosin-related kinase B (TrkB) receptor in the hippocampal and frontal cortex of infant Long-Evans rats. Levels of BDNF protein were increased in the hippocampus, but not frontal cortex, of alcohol-exposed rats 24h after the last dose, when compared with undisturbed (but not sham-intubated) control animals. BDNF protein levels showed a trend toward increase in hippocampus of sham-intubated animals as well, suggesting an effect of the intubation procedure. TrkB protein was increased in the hippocampus of alcohol-exposed animals compared to sham-intubated pups, indicating an alcohol-specific effect on receptor expression. In addition, expression of bdnf total mRNA in alcohol-exposed and sham-intubated pups was enhanced in the hippocampus; however, there was a differential effect of alcohol and intubation stress on exon I- and IV-specific mRNA transcripts. Further, plasma corticosterone was found to be increased in both alcohol-exposed and sham-intubated pups compared to undisturbed animals. Upregulation of BDNF could potentially represent a neuroprotective mechanism activated following alcohol exposure or stress. The results suggest that alcohol exposure and stress have both overlapping and unique effects on BDNF, and highlight the need for the stress of intubation to be taken into consideration in studies that implement this route of drug delivery.
相当于孕晚期的酒精暴露会导致海马体和皮质神经可塑性出现显著缺陷，从而引起树突分支、海马体成年神经发生以及学习任务表现的改变。本研究调查了新生期酒精暴露（出生后第4 - 9天，5.25克/千克/天）对幼龄Long-Evans大鼠海马体和额叶皮质中脑源性神经营养因子（BDNF）及原肌球蛋白相关激酶B（TrkB）受体表达的影响。与未受干扰（但非假插管）的对照动物相比，末次给药后24小时，酒精暴露大鼠海马体中的BDNF蛋白水平升高，但额叶皮质中未升高。假插管动物的海马体中BDNF蛋白水平也有升高趋势，提示插管操作有一定影响。与假插管幼崽相比，酒精暴露动物海马体中的TrkB蛋白增加，表明酒精对受体表达有特异性影响。此外，酒精暴露和假插管幼崽海马体中bdnf总mRNA的表达均增强；然而，酒精和插管应激对外显子I和IV特异性mRNA转录本有不同影响。此外，与未受干扰的动物相比，发现酒精暴露和假插管幼崽的血浆皮质酮均升高。BDNF的上调可能代表酒精暴露或应激后激活的一种神经保护机制。结果表明，酒精暴露和应激对BDNF既有重叠又有独特的影响，并强调在采用这种给药途径的研究中需要考虑插管应激。
