PMID- 24599793
OWN - NLM
STAT- MEDLINE
DCOM- 20141124
LR  - 20220310
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Linking)
VI  - 39
IP  - 4
DP  - 2014 Apr
TI  - Impairments in brain-derived neurotrophic factor-induced glutamate release in 
      cultured cortical neurons derived from rats with intrauterine growth retardation: 
      possible involvement of suppression of TrkB/phospholipase C-gamma activation.
PG  - 785-92
LID - 10.1007/s11064-014-1270-x [doi]
AB  - Low birth weight due to intrauterine growth retardation (IUGR) is suggested to be 
      a risk factor for various psychiatric disorders such as schizophrenia. It has 
      been reported that developmental cortical dysfunction and neurocognitive deficits 
      are observed in individuals with IUGR, however, the underlying molecular 
      mechanisms have yet to be elucidated. Brain-derived neurotrophic factor (BDNF) 
      and its receptor TrkB are associated with schizophrenia and play a role in 
      cortical development. We previously demonstrated that BDNF induced glutamate 
      release through activation of the TrkB/phospholipase C-gamma (PLC-gamma) pathway in 
      developing cultured cortical neurons, and that, using a rat model for IUGR caused 
      by maternal administration of thromboxane A2, cortical levels of TrkB were 
      significantly reduced in IUGR rats at birth. These studies prompted us to 
      hypothesize that TrkB reduction in IUGR cortex led to impairment of 
      BDNF-dependent glutamatergic neurotransmission. In the present study, we found 
      that BDNF-induced glutamate release was strongly impaired in cultured IUGR 
      cortical neurons where TrkB reduction was maintained. Impairment of BDNF-induced 
      glutamate release in IUGR neurons was ameliorated by transfection of human TrkB 
      (hTrkB). Although BDNF-stimulated phosphorylation of TrkB and of PLC-gamma was 
      decreased in IUGR neurons, the hTrkB transfection recovered the deficits in their 
      phosphorylation. These results suggest that TrkB reduction causes impairment of 
      BDNF-stimulated glutamatergic function via suppression of TrkB/PLC-gamma activation 
      in IUGR cortical neurons. Our findings provide molecular insights into how IUGR 
      links to downregulation of BDNF function in the cortex, which might be involved 
      in the development of IUGR-related diseases such as schizophrenia.
FAU - Numakawa, Tadahiro
AU  - Numakawa T
AD  - Department of Mental Disorder Research, National Institute of Neuroscience, 
      National Center of Neurology and Psychiatry, 4-1-1, Ogawa-Higashi, Kodaira, 
      Tokyo, 187-8502, Japan, numakawa@ncnp.go.jp.
FAU - Matsumoto, Tomoya
AU  - Matsumoto T
FAU - Ooshima, Yoshiko
AU  - Ooshima Y
FAU - Chiba, Shuichi
AU  - Chiba S
FAU - Furuta, Miyako
AU  - Furuta M
FAU - Izumi, Aiko
AU  - Izumi A
FAU - Ninomiya-Baba, Midori
AU  - Ninomiya-Baba M
FAU - Odaka, Haruki
AU  - Odaka H
FAU - Hashido, Kazuo
AU  - Hashido K
FAU - Adachi, Naoki
AU  - Adachi N
FAU - Kunugi, Hiroshi
AU  - Kunugi H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140306
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.1.4.3 (Phospholipase C gamma)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Cerebral Cortex/drug effects/*enzymology
MH  - Enzyme Activation/drug effects/physiology
MH  - Female
MH  - Fetal Growth Retardation/*enzymology
MH  - Glutamic Acid/*metabolism
MH  - Humans
MH  - Male
MH  - Neurons/drug effects/enzymology
MH  - Phospholipase C gamma/antagonists & inhibitors/*metabolism
MH  - Pregnancy
MH  - Rats
MH  - Rats, Long-Evans
MH  - Rats, Wistar
MH  - Receptor, trkB/antagonists & inhibitors/*metabolism
EDAT- 2014/03/07 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/03/07 06:00
PHST- 2013/11/10 00:00 [received]
PHST- 2014/02/25 00:00 [accepted]
PHST- 2014/02/10 00:00 [revised]
PHST- 2014/03/07 06:00 [entrez]
PHST- 2014/03/07 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - 10.1007/s11064-014-1270-x [doi]
PST - ppublish
SO  - Neurochem Res. 2014 Apr;39(4):785-92. doi: 10.1007/s11064-014-1270-x. Epub 2014 
      Mar 6.