PMID- 14604759
OWN - NLM
STAT- MEDLINE
DCOM- 20040219
LR  - 20190901
IS  - 0165-3806 (Print)
IS  - 0165-3806 (Linking)
VI  - 145
IP  - 2
DP  - 2003 Nov 12
TI  - Control of neuronal nitric oxide synthase and brain-derived neurotrophic factor 
      levels by GABA-A receptors in the developing rat cortex.
PG  - 185-95
AB  - Gamma-aminobutyric acid (GABA) plays an important morphogenetic role, acting 
      through GABA-A receptors, which are depolarizing in the developing rat brain. 
      Other molecules with major morphogenetic roles are the nitric oxide free radical 
      (NO(.)) and brain-derived neurotrophic factor (BDNF), both of which are involved 
      in the control of synaptic plasticity and apoptosis. In the present work, we 
      investigated the effect of GABA-A receptor activation on neuronal NO(.) synthase 
      (nNOS) and BDNF immunoreactivity in the developing cortex of 5-day-old rats. We 
      also determined the effect of GABA-A receptor activation on phosphorylated 
      cAMP-response element binding protein (pCREB) immunoreactivity in an effort to 
      elucidate the molecular mechanisms involved. Our results show that activation of 
      GABA-A receptors leads to increased numbers of nNOS, BDNF and pCREB, as well as 
      nNOS-pCREB and BDNF-pCREB doubly immunopositive cells. This effect is abolished 
      when L-type Ca(2+) channels are blocked. These results indicate that the 
      following mechanism could be operating: depolarization following GABA-A receptor 
      activation leads to opening of L-type voltage-gated calcium channels, resulting 
      in an increased Ca(2+) influx, which in turn leads to phosphorylation and, thus, 
      activation, of the transcription factor CREB; the phosphorylated CREB can then 
      induce BDNF, as well as nNOS.
FAU - Mantelas, A
AU  - Mantelas A
AD  - Laboratory of Biology--Biochemistry, School of Health Sciences, University of 
      Athens, Papadiamantopoulou 123, Athens 11527, Greece.
FAU - Stamatakis, A
AU  - Stamatakis A
FAU - Kazanis, I
AU  - Kazanis I
FAU - Philippidis, H
AU  - Philippidis H
FAU - Stylianopoulou, F
AU  - Stylianopoulou F
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Brain Res Dev Brain Res
JT  - Brain research. Developmental brain research
JID - 8908639
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (GABA Modulators)
RN  - 0 (GABA-A Receptor Agonists)
RN  - 0 (Receptors, GABA-A)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - Q3JTX2Q7TU (Diazepam)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Calcium Channel Blockers/pharmacology
MH  - Calcium Channels, L-Type/drug effects/metabolism
MH  - Calcium Signaling/physiology
MH  - Cell Differentiation/drug effects/physiology
MH  - Cerebral Cortex/cytology/*growth & development/*metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Diazepam/pharmacology
MH  - Female
MH  - GABA Modulators/pharmacology
MH  - GABA-A Receptor Agonists
MH  - Humans
MH  - Male
MH  - Membrane Potentials/physiology
MH  - Neurons/cytology/drug effects/*metabolism
MH  - Nitric Oxide/biosynthesis
MH  - Nitric Oxide Synthase/*metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, GABA-A/*metabolism
EDAT- 2003/11/08 05:00
MHDA- 2004/02/20 05:00
CRDT- 2003/11/08 05:00
PHST- 2003/11/08 05:00 [pubmed]
PHST- 2004/02/20 05:00 [medline]
PHST- 2003/11/08 05:00 [entrez]
AID - S0165380603002426 [pii]
AID - 10.1016/j.devbrainres.2003.08.001 [doi]
PST - ppublish
SO  - Brain Res Dev Brain Res. 2003 Nov 12;145(2):185-95. doi: 
      10.1016/j.devbrainres.2003.08.001.