Differential correlation of serum BDNF and microRNA content in rats with rapid or late onset of heavy alcohol use
| Autor: | David Darevesky, Ellanor L. Whiteley, Sophie Laguesse, Dorit Ron, Anthony L. Berger, Yann Ehinger, Marie Lordkipanidzé, Khanhky Phamluong, Samuel A. Sakhai, Jeffrey J. Moffat, Mélanie Welman, Mehdi Farokhnia, Lorenzo Leggio |
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| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Prefrontal Cortex Medicine (miscellaneous) Alcohol abuse Late onset Alcohol Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Neurotrophic factors Internal medicine medicine Animals Rats Long-Evans Platelet Prefrontal cortex Pharmacology business.industry Brain-Derived Neurotrophic Factor Patient Acuity medicine.disease Rats 030227 psychiatry Alcoholism MicroRNAs Psychiatry and Mental health Circulating MicroRNA Endocrinology chemistry business 030217 neurology & neurosurgery |
| Zdroj: | Addict Biol |
| ISSN: | 1369-1600 1355-6215 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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