Preferential increase in the hippocampal synaptic vesicle protein 2A (SV2A) by pentylenetetrazole kindling.
The present study evaluated the expressional levels of synaptic vesicle protein 2A (SV2A) and other secretary machinery proteins (i.e., soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes, Munc18-1, N-ethylmaleimide-sensitive factor (NSF) and soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP)) in a pentylenetetrazole (PTZ) kindling model. Repeated administration of sub-convulsive PTZ (40 mg/kg, i.p.) progressively increased seizure susceptibility in mice and consistently induced clonic seizures in most animals tested at 15 days after the treatment. Western blot analysis revealed that, among the secretary machinery proteins examined, hippocampal SV2A was selectively elevated by PTZ kindling. PTZ kindling-induced SV2A expression appeared region-specific and the SV2A levels in the cerebral cortex or cerebellum were unaltered. In addition, SV2A expression by PTZ kindling was prominent in the hilar region of the dentate gyrus (DG) where GABAergic interneurons are located, but not in other hippocampal regions (e.g., the stratum lucidum of the CA3 and synaptic layers surrounding CA1 or CA3 pyramidal neurons). These findings suggest that PTZ kindling preferentially elevates SV2A expression in the hippocampus probably as a compensatory mechanism to activate the inhibitory neurotransmission.
Ohno
Yukihiro
Y
Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka 569-1094, Japan.
Ishihara
Shizuka
S
Terada
Ryo
R
Kikuta
Miki
M
Sofue
Nobumasa
N
Kawai
Yoshiko
Y
Serikawa
Tadao
T
Sasa
Masashi
M
D000818:Animals; D003292:Convulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007696:Kindling, Neurologic / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D008815:Mice, Inbred Strains; D051938:Munc18 Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D010433:Pentylenetetrazole / Q000494:pharmacology; D050600:SNARE Proteins / Q000378:metabolism; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D003292:Convulsants; D008562:Membrane Glycoproteins; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D050600:SNARE Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; C489614:Sv2a protein, mouse; D010433:Pentylenetetrazole