Cocaine-mediated activation of microglia and microglial MeCP2 and BDNF production.

Cocaine-mediated activation of microglia and microglial MeCP2 and BDNF production.
Neurobiol Dis. 2018 May 30;:
Authors: Cotto B, Li H, Tuma RF, Ward SJ, Langford D
Abstract
The molecular substrates underlying cocaine reinforcement and addiction have been studied for decades, with a primary focus on signaling molecules involved in modulation of neuronal communication. Brain-derived neurotrophic factor (BDNF) is an important signaling molecule involved in neuronal dendrite and spine modulation. Methyl CpG binding protein 2 (MeCP2) binds to the promoter region of BDNF to negatively regulate its expression and cocaine can recruit MeCP2 to alter the expression of genes such as BDNF that are involved in synaptic plasticity. For several decades, BDNF has been implicated in mediating synaptic plasticity associated with cocaine abuse, and most studies report that neurons are the primary source for BDNF production in the brain. The current study assessed the effects of intravenous cocaine self-administration on microglial activation, and MeCP2 and BDNF expression in reward regions of the brain in vivo, as well as determined specific effects of cocaine exposure on MeCP2 and BDNF expression in human primary neurons and microglia. The results from this study highlight a distinct molecular pathway in microglia through which cocaine increases BDNF, including the phosphorylation of MeCP2 its subsequent translocation from the nucleus to the cytosol,...

Source: Neurobiology of Disease - May 30, 2018 Category: Neurology Authors: Cotto B, Li H, Tuma RF, Ward SJ, Langford D Tags: Neurobiol Dis Source Type: research