PMID- 28722769
OWN - NLM
STAT- MEDLINE
DCOM- 20171009
LR  - 20190126
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 143
IP  - 1
DP  - 2017 Oct
TI  - Promoter IV-BDNF deficiency disturbs cholinergic gene expression of CHRNA5, 
      CHRM2, and CHRM5: effects of drug and environmental treatments.
PG  - 49-64
LID - 10.1111/jnc.14129 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) promotes maturation of cholinergic 
      neurons. However, how activity-dependent BDNF expression affects specific 
      cholinergic gene expression remains unclear. This study addressed this question 
      by determining mRNA levels of 22 acetylcholine receptor subunits, the choline 
      transporter (CHT), and the choline acetyltransferase (ChAT) in mice deficient in 
      activity-dependent BDNF via promoter IV (KIV) and control wild-type mice. 
      Quantitative RT-PCR revealed significant reductions in nicotinic acetylcholine 
      receptor alpha 5 (CHRNA5) in the frontal cortex and hippocampus and M5 muscarinic 
      acetylcholine receptor (CHRM5) in the hippocampus, but significant increases in 
      M2 muscarinic acetylcholine receptor (CHRM2) in the frontal cortex of KIV mice 
      compared to wild-type mice. Three-week treatments with fluoxetine, phenelzine, 
      duloxetine, imipramine, or an enriched environment treatment (EET) did not affect 
      the altered expression of these genes except that EET increased CHRNA5 levels 
      only in KIV frontal cortex. EET also increased levels of CHRNA7, CHT, and ChAT, 
      again only in the KIV frontal cortex. The imipramine treatment was most prominent 
      among the four antidepressants; it up-regulated hippocampal CHRM2 and frontal 
      cortex CHRM5 in both genotypes, and frontal cortex CHRNA7 only in KIV mice. To 
      the best of our knowledge, this is the first evidence that BDNF deficiency 
      disturbs expression of CHRNA5, CHRM2, and CHRM5. Our results suggest that 
      promoter IV-BDNF deficiency - which occurs under chronic stress - causes 
      cholinergic dysfunctions via these receptors. EET is effective on CHRNA5, while 
      its compensatory induction of other cholinergic genes or drugs targeting CHRNA5, 
      CHRM2, and CHRM5 may become an alternative strategy to reverse these BDNF-linked 
      cholinergic dysfunctions.
CI  - (c) 2017 International Society for Neurochemistry.
FAU - Sakata, Kazuko
AU  - Sakata K
AUID- ORCID: 0000-0001-6509-216X
AD  - Department of Pharmacology, University of Tennessee Health Science Center, 
      Memphis, TN, USA.
FAU - Overacre, Abigail E
AU  - Overacre AE
AD  - Department of Pharmacology, University of Tennessee Health Science Center, 
      Memphis, TN, USA.
LA  - eng
GR  - R03 MH102445/MH/NIMH NIH HHS/United States
GR  - R21 MH105567/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20170816
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (CHRM2 protein, human)
RN  - 0 (CHRNA5 protein, mouse)
RN  - 0 (Receptor, Muscarinic M2)
RN  - 0 (Receptor, Muscarinic M5)
RN  - 0 (Receptors, Nicotinic)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*pharmacology
MH  - Brain-Derived Neurotrophic Factor/*deficiency/genetics
MH  - *Environment
MH  - Female
MH  - Frontal Lobe/drug effects/metabolism
MH  - Gene Expression
MH  - Hippocampus/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Mice, 129 Strain
MH  - Mice, Inbred C57BL
MH  - Promoter Regions, Genetic/drug effects/physiology
MH  - Receptor, Muscarinic M2/*biosynthesis/genetics
MH  - Receptor, Muscarinic M5/*biosynthesis/genetics
MH  - Receptors, Nicotinic/*biosynthesis/genetics
PMC - PMC5672805
MID - NIHMS912252
OTO - NOTNLM
OT  - BDNF
OT  - acetylcholine
OT  - antidepressants
OT  - enriched environment treatment
OT  - gene expression
OT  - promoter IV
COIS- Conflict of interest The authors declare no conflict of interest.
EDAT- 2017/07/20 06:00
MHDA- 2017/10/11 06:00
PMCR- 2017/11/06
CRDT- 2017/07/20 06:00
PHST- 2017/05/31 00:00 [received]
PHST- 2017/07/05 00:00 [revised]
PHST- 2017/07/13 00:00 [accepted]
PHST- 2017/07/20 06:00 [pubmed]
PHST- 2017/10/11 06:00 [medline]
PHST- 2017/07/20 06:00 [entrez]
PHST- 2017/11/06 00:00 [pmc-release]
AID - 10.1111/jnc.14129 [doi]
PST - ppublish
SO  - J Neurochem. 2017 Oct;143(1):49-64. doi: 10.1111/jnc.14129. Epub 2017 Aug 16.