PMID- 29859319
OWN - NLM
STAT- MEDLINE
DCOM- 20190906
LR  - 20240328
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Print)
IS  - 0969-9961 (Linking)
VI  - 117
DP  - 2018 Sep
TI  - Cocaine-mediated activation of microglia and microglial MeCP2 and BDNF 
      production.
PG  - 28-41
LID - S0969-9961(18)30155-4 [pii]
LID - 10.1016/j.nbd.2018.05.017 [doi]
AB  - 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, which frees the BDNF promoter and permits its 
      transcriptional activation. Results from these studies show for the first time 
      that cocaine self-administration increases microglial activation, and that 
      microglial MeCP2 is a sensitive target of cocaine resulting in increased release 
      of BDNF from microglia, and possibly contributing to cocaine-induced synaptic 
      plasticity.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Cotto, Bianca
AU  - Cotto B
AD  - Department of Neuroscience, Lewis Katz School of Medicine at Temple University, 
      Philadelphia, PA 19140, USA.
FAU - Li, Hongbo
AU  - Li H
AD  - Department of Pharmacology, Lewis Katz School of Medicine at Temple University, 
      Philadelphia, PA 19140, USA.
FAU - Tuma, Ronald F
AU  - Tuma RF
AD  - Department of Pharmacology, Lewis Katz School of Medicine at Temple University, 
      Philadelphia, PA 19140, USA.
FAU - Ward, Sara Jane
AU  - Ward SJ
AD  - Department of Pharmacology, Lewis Katz School of Medicine at Temple University, 
      Philadelphia, PA 19140, USA.
FAU - Langford, Dianne
AU  - Langford D
AD  - Department of Neuroscience, Lewis Katz School of Medicine at Temple University, 
      Philadelphia, PA 19140, USA. Electronic address: tdl@temple.edu.
LA  - eng
GR  - P01 DA037830/DA/NIDA NIH HHS/United States
GR  - P30 DA013429/DA/NIDA NIH HHS/United States
GR  - P30 MH092177/MH/NIMH NIH HHS/United States
GR  - R25 MH080661/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180530
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Bdnf protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Mecp2 protein, rat)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/agonists/*biosynthesis
MH  - Cells, Cultured
MH  - Cocaine/*administration & dosage
MH  - Dopamine Uptake Inhibitors/*administration & dosage
MH  - Humans
MH  - Male
MH  - Methyl-CpG-Binding Protein 2/agonists/*biosynthesis
MH  - Microglia/*drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Self Administration
PMC - PMC6051925
MID - NIHMS972855
OTO - NOTNLM
OT  - Cocaine
OT  - Microglia
OT  - Neuron
EDAT- 2018/06/03 06:00
MHDA- 2019/09/07 06:00
PMCR- 2019/09/01
CRDT- 2018/06/03 06:00
PHST- 2017/11/14 00:00 [received]
PHST- 2018/05/09 00:00 [revised]
PHST- 2018/05/29 00:00 [accepted]
PHST- 2018/06/03 06:00 [pubmed]
PHST- 2019/09/07 06:00 [medline]
PHST- 2018/06/03 06:00 [entrez]
PHST- 2019/09/01 00:00 [pmc-release]
AID - S0969-9961(18)30155-4 [pii]
AID - 10.1016/j.nbd.2018.05.017 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2018 Sep;117:28-41. doi: 10.1016/j.nbd.2018.05.017. Epub 2018 May 
      30.