PMID- 19545402
OWN - NLM
STAT- MEDLINE
DCOM- 20110502
LR  - 20231213
IS  - 1756-6606 (Electronic)
IS  - 1756-6606 (Linking)
VI  - 2
DP  - 2009 Jun 22
TI  - Maternal epileptic seizure induced by pentylenetetrazol: apoptotic 
      neurodegeneration and decreased GABAB1 receptor expression in prenatal rat brain.
PG  - 20
LID - 10.1186/1756-6606-2-20 [doi]
AB  - Epilepsy is a prominent sign of neurological dysfunction in children with various 
      fetal and maternal deficiencies. However, the detailed mechanism and influences 
      underlying epileptic disorders are still unrevealed. The hippocampal neurons are 
      vulnerable to epilepsy-induced pathologic changes and often manifests as neuronal 
      death. The present study was designed to investigate the effect of maternal 
      epileptic seizure on apoptotic neuronal death, modulation of GABAB1 receptor (R), 
      and protein kinase A-alpha (PKA) in prenatal rat hippocampal neurons at 
      gestational days (GD) 17.5. Seizure was induced in pregnant rat using 
      intraperitoneal injection of pentylenetetrazol (PTZ) (40 mg/kg for 15 days). To 
      confirm the seizure electroencephalography (EEG) data was obtained by the Laxtha 
      EEG-monitoring device in the EEG recording room and EEG were monitored 5 min and 
      15 min after PTZ injection. The RT-PCR and Western blot results showed 
      significant increased expression of cytochrome-c and caspases-3, while decreased 
      levels of GABAB1R, and PKA protein expression upon ethanol, PTZ and ethanol plus 
      PTZ exposure in primary neuronal cells cultured from PTZ-induced seizure model as 
      compare to non-PTZ treated maternal group. Apoptotic neurodegeneration was 
      further confirmed with Fluoro-Jade B and propidium iodide staining, where neurons 
      were scattered and shrunken, with markedly condensed nuclei in PTZ treated group 
      compared with control. This study for the first time indicate that PTZ-induced 
      seizures triggered activation of caspases-3 to induce widespread apoptotic 
      neuronal death and decreased GABAB1R expression in hippocampal neurons, providing 
      a possible mechanistic link between maternal epilepsy induced neurodegeneration 
      alteration of GABAB1R and PKA expression level during prenatal brain development. 
      This revealed new aspects of PTZ and ethanol's modulation on GABAB1R, learning 
      and memory. Further, explain the possibility that children delivered by epileptic 
      mothers may have higher risk of developmental disturbances and malformations.
FAU - Naseer, Muhammad Imran
AU  - Naseer MI
AD  - Division of Life Science, College of Natural Sciences and Applied Life Science 
      (Brain Korea 21), Gyeongsang National University, Chinju, 660-701, Republic of 
      Korea. mimrannaseer@yahoo.com
FAU - Shupeng, Li
AU  - Shupeng L
FAU - Kim, Myeong Ok
AU  - Kim MO
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090622
PL  - England
TA  - Mol Brain
JT  - Molecular brain
JID - 101468876
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, GABA-B)
RN  - 9007-43-6 (Cytochromes c)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 3.4.22.- (Caspase 3)
RN  - WM5Z385K7T (Pentylenetetrazole)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Brain/*embryology/metabolism/physiopathology
MH  - Caspase 3/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/genetics/metabolism
MH  - Cytochromes c/metabolism
MH  - Electroencephalography
MH  - Epilepsy/complications/*pathology/physiopathology
MH  - Female
MH  - Fetus/*metabolism/pathology/physiopathology
MH  - Gene Expression Regulation, Developmental
MH  - Hippocampus/embryology/enzymology/pathology/physiopathology
MH  - *Maternal Exposure
MH  - Mitochondria/metabolism
MH  - Nerve Degeneration/complications/*pathology
MH  - Neurons/enzymology/pathology
MH  - Pentylenetetrazole
MH  - Pregnancy
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Receptors, GABA-B/genetics/*metabolism
PMC - PMC2706809
EDAT- 2009/06/24 09:00
MHDA- 2011/05/03 06:00
PMCR- 2009/06/22
CRDT- 2009/06/24 09:00
PHST- 2009/04/21 00:00 [received]
PHST- 2009/06/22 00:00 [accepted]
PHST- 2009/06/24 09:00 [entrez]
PHST- 2009/06/24 09:00 [pubmed]
PHST- 2011/05/03 06:00 [medline]
PHST- 2009/06/22 00:00 [pmc-release]
AID - 1756-6606-2-20 [pii]
AID - 10.1186/1756-6606-2-20 [doi]
PST - epublish
SO  - Mol Brain. 2009 Jun 22;2:20. doi: 10.1186/1756-6606-2-20.