FMRP regulates an ethanol-dependent shift in GABABR function and expression with rapid antidepressant properties
| Autor: | Farr Niere, Luisa P. Cacheaux, Chelcie F. Heaney, Michael R. Drew, Sarah A. Wolfe, Sean P. Farris, Kimberly F. Raab-Graham, Emily R. Workman, R. Adron Harris, Sanjeev Namjoshi, Boris V. Zemelman |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.drug_class Science Regulator General Physics and Astronomy chemistry.chemical_element Alcohol Pharmacology GABAB receptor Calcium Anxiolytic General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Receptor Multidisciplinary Ethanol General Chemistry 030104 developmental biology Endocrinology chemistry Antidepressant 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications, Vol 7, Iss 1, Pp 1-13 (2016) |
| ISSN: | 2041-1723 |
| Popis: | Alcohol promotes lasting neuroadaptive changes that may provide relief from depressive symptoms, often referred to as the self-medication hypothesis. However, the molecular/synaptic pathways that are shared by alcohol and antidepressants are unknown. In the current study, acute exposure to ethanol produced lasting antidepressant and anxiolytic behaviours. To understand the functional basis of these behaviours, we examined a molecular pathway that is activated by rapid antidepressants. Ethanol, like rapid antidepressants, alters γ-aminobutyric acid type B receptor (GABABR) expression and signalling, to increase dendritic calcium. Furthermore, new GABABRs are synthesized in response to ethanol treatment, requiring fragile-X mental retardation protein (FMRP). Ethanol-dependent changes in GABABR expression, dendritic signalling, and antidepressant efficacy are absent in Fmr1-knockout (KO) mice. These findings indicate that FMRP is an important regulator of protein synthesis following alcohol exposure, providing a molecular basis for the antidepressant efficacy of acute ethanol exposure. |
| Databáze: | OpenAIRE |
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