Department of Neurology, University of California, San Francisco, San Francisco, California.
Research Center, Montreal Heart Institute, Montreal, Quebec, Canada.
Addict Biol. 2021 Mar;26(2):e12890. doi: 10.1111/adb.12890. Epub 2020 Mar 5.
Heavy alcohol use reduces the levels of the brain-derived neurotrophic factor (BDNF) in the prefrontal cortex of rodents through the upregulation of microRNAs (miRs) targeting BDNF mRNA. In humans, an inverse correlation exists between circulating blood levels of BDNF and the severity of psychiatric disorders including alcohol abuse. Here, we set out to determine whether a history of heavy alcohol use produces comparable alterations in the blood of rats. We used an intermittent access to 20% alcohol using the two-bottle choice paradigm (IA20%2BC) and measured circulating levels of BDNF protein and miRs targeting BDNF in the serum of Long-Evans rats before and after 8 weeks of excessive alcohol intake. We observed that the drinking profile of heavy alcohol users is not unified, whereas 70% of the rats gradually escalate their alcohol intake (late onset), and 30% of alcohol users exhibit a very rapid onset of drinking (rapid onset). We found that serum BDNF levels are negatively correlated with alcohol intake in both rapid onset and late onset rats. In contrast, increased expression of the miRs targeting BDNF, miR30a-5p, miR-195-5p, miR191-5p and miR206-3p, was detected only in the rapid onset rats. Finally, we report that the alcohol-dependent molecular changes are not due to alterations in platelet number. Together, these data suggest that rats exhibit both late and rapid onset of alcohol intake. We further show that heavy alcohol use produces comparable changes in BDNF protein levels in both groups. However, circulating microRNAs are responsive to alcohol only in the rapid onset rats.
大量饮酒通过上调针对 BDNF mRNA 的 microRNAs（miRs），降低啮齿动物前额皮质中的脑源性神经营养因子（BDNF）水平。在人类中，BDNF 的循环血液水平与包括酒精滥用在内的精神疾病的严重程度呈负相关。在这里，我们着手确定大量饮酒是否会在大鼠的血液中产生类似的改变。我们使用间歇接触 20%酒精的双瓶选择范式（IA20%2BC），并在 Long-Evans 大鼠摄入过量酒精 8 周前后测量血清中 BDNF 蛋白和针对 BDNF 的 miRs 的循环水平。我们观察到，大量饮酒者的饮酒模式并不统一，而 70%的大鼠逐渐增加饮酒量（晚期开始），而 30%的饮酒者则表现出非常快速的饮酒开始（快速开始）。我们发现，血清 BDNF 水平与快速开始和晚期开始大鼠的酒精摄入量呈负相关。相比之下，只有快速开始的大鼠中检测到针对 BDNF 的 miRs 的表达增加，即 miR30a-5p、miR-195-5p、miR191-5p 和 miR206-3p。最后，我们报告说，酒精依赖的分子变化不是由于血小板数量的改变引起的。总之，这些数据表明大鼠表现出晚期和快速开始的饮酒。我们进一步表明，大量饮酒在两组大鼠中均产生了类似的 BDNF 蛋白水平变化。然而，只有在快速开始的大鼠中，循环 microRNAs 才对酒精有反应。
