PMID- 18501512 OWN - NLM STAT- MEDLINE DCOM- 20080924 LR - 20141120 IS - 0304-3940 (Print) IS - 0304-3940 (Linking) VI - 439 IP - 1 DP - 2008 Jul 4 TI - Stimulatory effects of a melatonin receptor agonist, ramelteon, on BDNF in mouse cerebellar granule cells. PG - 34-6 LID - 10.1016/j.neulet.2008.04.099 [doi] AB - Melatonin receptor activation has been linked to the regulation of neurotrophic factors, including the brain-derived neurotrophic factor (BDNF). To further characterize the effects of melatonin receptor stimulation on neuronal BDNF, we used a clinically available novel agonist for MT1 and MT2 melatonin receptors, ramelteon. Primary cultures of cerebellar granule cells (CGC) have been established as an in vitro model for studying neuronal BDNF. We took advantage of the availability of MT1- and MT2-deficient (knockout; KO) mice to employ primary CGC prepared from wild type (WT), MT1 KO, and MT2 KO mice. We investigated the effects of ramelteon on BDNF protein and mRNA content. Administered in a low nanomolar range, ramelteon increased BDNF protein content in all three types of mouse CGC. This ramelteon-triggered BDNF protein elevation was not preceded by a BDNF mRNA increase. However, it was prevented by treatment of cultures with a protein synthesis inhibitor cycloheximide. These results demonstrated that the MT1/MT2 melatonin receptor agonist ramelteon is capable of increasing BDNF protein in neurons expressing either of the two melatonin receptor types and that this action of ramelteon involves translational mechanisms. Further research is needed to explore the putative influence of ramelteon on BDNF-associated neuroplasticity. FAU - Imbesi, Marta AU - Imbesi M AD - The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 1601 West Taylor Street, MC912 Chicago, IL 60612, USA. FAU - Uz, Tolga AU - Uz T FAU - Dzitoyeva, Svetlana AU - Dzitoyeva S FAU - Manev, Hari AU - Manev H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080502 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Indenes) RN - 0 (Protein Synthesis Inhibitors) RN - 0 (RNA, Messenger) RN - 0 (Receptor, Melatonin, MT1) RN - 0 (Receptor, Melatonin, MT2) RN - 901AS54I69 (ramelteon) RN - 98600C0908 (Cycloheximide) SB - IM MH - Animals MH - Animals, Newborn MH - Brain-Derived Neurotrophic Factor/classification/genetics/*metabolism MH - Cells, Cultured MH - Cerebellum/*cytology MH - Cycloheximide/pharmacology MH - Drug Interactions MH - Gene Expression Regulation/*drug effects/genetics MH - Indenes/*pharmacology MH - Mice MH - Mice, Knockout MH - Neurons/*drug effects MH - Protein Synthesis Inhibitors/pharmacology MH - RNA, Messenger/metabolism MH - Receptor, Melatonin, MT1/deficiency MH - Receptor, Melatonin, MT2/deficiency MH - Time Factors EDAT- 2008/05/27 09:00 MHDA- 2008/09/25 09:00 CRDT- 2008/05/27 09:00 PHST- 2008/03/24 00:00 [received] PHST- 2008/04/29 00:00 [revised] PHST- 2008/04/30 00:00 [accepted] PHST- 2008/05/27 09:00 [pubmed] PHST- 2008/09/25 09:00 [medline] PHST- 2008/05/27 09:00 [entrez] AID - S0304-3940(08)00605-8 [pii] AID - 10.1016/j.neulet.2008.04.099 [doi] PST - ppublish SO - Neurosci Lett. 2008 Jul 4;439(1):34-6. doi: 10.1016/j.neulet.2008.04.099. Epub 2008 May 2.