Differential correlation of serum BDNF and microRNA content in rats with rapid or late onset of heavy alcohol use. (5th March 2020)

• Record Type: Journal Article
• Authors: Ehinger, Yann; Phamluong, Khanhky; Darevesky, David; Welman, Melanie; Moffat, Jeffrey J.; Sakhai, Samuel A.; Whiteley, Ellanor L.; Berger, Anthony L.; Laguesse, Sophie; Farokhnia, Mehdi; Leggio, Lorenzo; Lordkipanidzé, Marie; Ron, Dorit
• Is Part Of: Addiction biology. Volume 26:Number 2(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-03-05
• Subjects: alcohol -- BDNF -- microRNA; Substance abuse -- Periodicals; Substance abuse -- Physiological aspects -- Periodicals; Substance-Related Disorders -- periodicals; 616.86
• DOI: 10.1111/adb.12890
• Languages: English
• ISSNs: 1355-6215

Abstract

Abstract: 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. Abstract : Ehinger et al reports that Long‐Evans rats that excessively drink alcohol can be divided into rats exhibiting a rapid onset of alcohol drinking profile and rats that gradually escalate their intake. Serum BDNF is reduced in both groups of animals. In contrast, microRNAs targeting BDNF are elevated only in the serum of the rapid onset of drinking subjects.