PMID- 10553579
OWN - NLM
STAT- MEDLINE
DCOM- 19991215
LR  - 20190831
IS  - 0015-5691 (Print)
IS  - 0015-5691 (Linking)
VI  - 114
IP  - 3
DP  - 1999 Sep
TI  - [Molecular mechanism underlying epileptic seizure: forwards development of novel 
      drugs for untreatable epilepsy].
PG  - 161-8
AB  - For the development of new drugs for hitherto untreatable epilepsy, it is 
      necessary to clarify the basic pathophysiology involved in such epileptic 
      seizures and find the target site. This review focused on molecular events 
      related to the expression and expansion of the epileptic focus which are the 
      target of novel antiepileptics. Immediate early genes such as c-fos followed by 
      expression of nerve growth factor (NGF) and brain-derived neurotrophic factor 
      (BDNF) have been evidenced as initial important phenomena in the cascade of 
      molecular systems that develop and complement the transient neuronal excitation 
      to long-term neuronal plasticity. Non-receptor type tyrosine kinase Fyn in the 
      Src family has been suggested to promote kindling development via tyrosine 
      phosphorylation of the NMDA-receptor subunit, NR2B. The cause of abnormality in 
      the inhibitory system is induced by lowering of glutamate-dependent GABA release 
      in the epileptic focus within the hippocampus in human temporal epilepsy. This is 
      probably attributed to a decrease in GABA transporters. Regarding abnormality of 
      the excitatory system, there is an increase in glutamate release prior to 
      convulsive seizures, an enhancement of NMDA receptor responsiveness and high 
      levels of AMPA receptors related to convulsion after completion of kindling. In 
      gene analysis of human familiar epilepsy, abnormalities and point mutations have 
      recently been found in the following genes: KCNQ 2 and KCNQ3, coding for K+ 
      channels; CHRNA4 of the nicotinic receptor subunit alpha 4; and the cystatin B 
      gene. In epilepsy model mice, EL mice with several gene mutations known to be 
      involved in the seizures, the El-1 gene contains an abnormality of the 
      ceruloplasmin gene. SER (spontaneously epileptic rat: zi/zi, tm/tm), a double 
      mutant, manifests a deletion of the region containing the aspartoacylase gene 
      related to the tm gene. Since an increase in N-acetyl-L-aspartate (NAA) is 
      observed in the SER brain, NAA may serve to evoke seizures.
FAU - Omori, K
AU  - Omori K
AD  - Department of Pharmacology, Kansai Medical University, Osaka, Japan.
FAU - Inagaki, C
AU  - Inagaki C
FAU - Sasa, M
AU  - Sasa M
LA  - jpn
PT  - English Abstract
PT  - Journal Article
PT  - Review
PL  - Japan
TA  - Nihon Yakurigaku Zasshi
JT  - Nihon yakurigaku zasshi. Folia pharmacologica Japonica
JID - 0420550
RN  - 0 (Anticonvulsants)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Potassium Channels)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, AMPA)
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 997-55-7 (N-acetylaspartate)
RN  - EC 1.16.3.1 (Ceruloplasmin)
RN  - EC 2.7.10.2 (FYN protein, human)
RN  - EC 2.7.10.2 (Fyn protein, mouse)
RN  - EC 2.7.10.2 (Fyn protein, rat)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn)
RN  - EC 3.5.- (Amidohydrolases)
RN  - EC 3.5.1.15 (aspartoacylase)
SB  - IM
MH  - Amidohydrolases/genetics
MH  - Animals
MH  - *Anticonvulsants
MH  - Aspartic Acid/analogs & derivatives/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Ceruloplasmin/genetics
MH  - Disease Models, Animal
MH  - *Epilepsy/genetics
MH  - Genes, fos
MH  - Hippocampus/metabolism
MH  - Humans
MH  - Kindling, Neurologic
MH  - Mice
MH  - Nerve Growth Factors/metabolism
MH  - Potassium Channels/genetics
MH  - Proto-Oncogene Proteins/physiology
MH  - Proto-Oncogene Proteins c-fyn
MH  - Rats
MH  - Receptors, AMPA/metabolism
MH  - gamma-Aminobutyric Acid/metabolism
RF  - 45
EDAT- 1999/12/20 00:00
MHDA- 1999/12/20 00:01
CRDT- 1999/12/20 00:00
PHST- 1999/12/20 00:00 [pubmed]
PHST- 1999/12/20 00:01 [medline]
PHST- 1999/12/20 00:00 [entrez]
AID - 10.1254/fpj.114.161 [doi]
PST - ppublish
SO  - Nihon Yakurigaku Zasshi. 1999 Sep;114(3):161-8. doi: 10.1254/fpj.114.161.