Differential Correlation of Serum BDNF and microRNA Content in Rats with Rapid or Late Onset of Heavy Alcohol Use
Differential Correlation of Serum BDNF and microRNA Content in Rats with Rapid or Late Onset of Heavy Alcohol Use
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 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 2-bottle choice paradigm (IA20%2BC), and measured circulating levels of BDNF protein and microRNAs 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), 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 microRNAs (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. Our 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.
Leggio Lorenzo、Ehinger Yann、Welman Melanie、Farokhnia Mehdi、Sakhai Samuel A.、Ron Dorit、Laguesse Sophie、Moffat Jeffrey J.、Berger Anthony L.、Whiteley Ellanor L.、Lordkipanidz¨| Marie、Phamluong Khanhky、Darevesky David
Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research and National Institutes of Health||Medication Development Program, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health||Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown UniversityDepartment of Neurology, University of CaliforniaResearch center, Montreal Heart InstituteClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research and National Institutes of Health||Medication Development Program, National Institute on Drug Abuse Intramural Research Program, National Institutes of HealthDepartment of Neurology, University of CaliforniaDepartment of Neurology, University of CaliforniaDepartment of Neurology, University of CaliforniaDepartment of Neurology, University of CaliforniaDepartment of Neurology, University of CaliforniaDepartment of Neurology, University of CaliforniaResearch center, Montreal Heart Institute||Faculty of pharmacy, University of MontrealDepartment of Neurology, University of CaliforniaDepartment of Neurology, University of California
基础医学神经病学、精神病学分子生物学
Leggio Lorenzo,Ehinger Yann,Welman Melanie,Farokhnia Mehdi,Sakhai Samuel A.,Ron Dorit,Laguesse Sophie,Moffat Jeffrey J.,Berger Anthony L.,Whiteley Ellanor L.,Lordkipanidz¨| Marie,Phamluong Khanhky,Darevesky David.Differential Correlation of Serum BDNF and microRNA Content in Rats with Rapid or Late Onset of Heavy Alcohol Use[EB/OL].(2025-03-28)[2025-05-04].https://www.biorxiv.org/content/10.1101/2019.12.18.881680.点此复制
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