PMID- 12941455
OWN - NLM
STAT- MEDLINE
DCOM- 20031117
LR  - 20190827
IS  - 0169-328X (Print)
IS  - 0169-328X (Linking)
VI  - 116
IP  - 1-2
DP  - 2003 Aug 19
TI  - Effect of zonisamide on molecular regulation of glutamate and GABA transporter 
      proteins during epileptogenesis in rats with hippocampal seizures.
PG  - 1-6
AB  - Epileptiform discharges and behavioral seizures may be the consequences of excess 
      excitation associated with the neurotransmitter glutamate, or from inadequate 
      inhibitory effects associated with gamma-aminobutyric acid (GABA). Synaptic 
      effects of these neurotransmitters are terminated by the action of transporter 
      proteins that remove amino acids from the synaptic cleft. Excitation initiated by 
      the synaptic release of glutamate is attenuated by the action of glial 
      transporters glutamate-aspartate transporter (GLAST) and glutamate transporter-1 
      (GLT-1), and the neuronal transporter excitatory amino-acid carrier-1 (EAAC-1). 
      GABA is removed from synaptic regions by the action of the transporters proteins 
      GABA transporter-1 (GAT-1) and GABA transporter-3 (GAT-3). In this experiment, 
      albino rats with chronic, spontaneous recurrent seizures induced by the amygdalar 
      injection of FeCl3 were treated for 14 days with zonisamide (ZNS) (40 mg/kg, 
      i.p.). Control animals underwent saline injection into the same amygdalar 
      regions. Treatment control for both groups of intracerebrally injected animals 
      was i.p. injection of equal volumes of saline. Western blotting was used to 
      measure the quantity of glutamate and GABA transporters in hippocampus and 
      frontal cortex. ZNS caused increase in the quantity of EAAC-1 protein in 
      hippocampus and cortex and down regulation of the GABA transporter GAT-1. These 
      changes occurred in both experimental and ZNS treated control animals. These data 
      show that the molecular effect of ZNS, with up-regulation of EAAC-1 and decreased 
      production of GABA transporters, should result in increased tissue and synaptic 
      concentrations of GABA. Although many antiepileptic drugs have effects on ion 
      channels when measured in vitro our study suggests that additional mechanisms of 
      action may be operant. Molecular effects on regulation of transporter proteins 
      may aid in understanding epileptogenesis and inform investigators about future 
      design and development of drugs to treat epilepsy.
FAU - Ueda, Yuto
AU  - Ueda Y
AD  - Department of Psychiatry, Miyazaki Medical College, 5200 Kihara, Kiyotake, 
      Miyazaki 889-1692, Japan. usan@post1.miyazaki-med.ac.jp
FAU - Doi, Taku
AU  - Doi T
FAU - Tokumaru, Jun
AU  - Tokumaru J
FAU - Willmore, L James
AU  - Willmore LJ
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Brain Res Mol Brain Res
JT  - Brain research. Molecular brain research
JID - 8908640
RN  - 0 (Amino Acid Transport System X-AG)
RN  - 0 (Anticonvulsants)
RN  - 0 (Carrier Proteins)
RN  - 0 (Chlorides)
RN  - 0 (Ferric Compounds)
RN  - 0 (GABA Plasma Membrane Transport Proteins)
RN  - 0 (Isoxazoles)
RN  - 0 (Membrane Proteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Organic Anion Transporters)
RN  - 0 (Slc6a1 protein, rat)
RN  - 459384H98V (Zonisamide)
RN  - U38V3ZVV3V (ferric chloride)
SB  - IM
MH  - Amino Acid Transport System X-AG/*metabolism
MH  - Amygdala/drug effects
MH  - Animals
MH  - Anticonvulsants/*pharmacology
MH  - Blotting, Western
MH  - Carrier Proteins/*metabolism
MH  - Chlorides
MH  - Chronic Disease
MH  - Disease Models, Animal
MH  - Epilepsy/chemically induced/genetics/*metabolism
MH  - Ferric Compounds/toxicity
MH  - Frontal Lobe/drug effects/metabolism
MH  - GABA Plasma Membrane Transport Proteins
MH  - Hippocampus/*drug effects/metabolism
MH  - Isoxazoles/*pharmacology
MH  - Male
MH  - Membrane Proteins/*metabolism
MH  - *Membrane Transport Proteins
MH  - *Organic Anion Transporters
MH  - Rats
MH  - Rats, Wistar
MH  - Zonisamide
EDAT- 2003/08/28 05:00
MHDA- 2003/12/03 05:00
CRDT- 2003/08/28 05:00
PHST- 2003/08/28 05:00 [pubmed]
PHST- 2003/12/03 05:00 [medline]
PHST- 2003/08/28 05:00 [entrez]
AID - S0169328X03001839 [pii]
AID - 10.1016/s0169-328x(03)00183-9 [doi]
PST - ppublish
SO  - Brain Res Mol Brain Res. 2003 Aug 19;116(1-2):1-6. doi: 
      10.1016/s0169-328x(03)00183-9.