Long-term increase of Sp-1 transcription factors in the hippocampus after kainic acid treatment.
Systemic administration of kainic acid (KA), a glutamate receptor agonist, causes robust seizures and has been used as an excellent rodent model for human temporal lobe epilepsy. Recently, we have demonstrated that a single injection of KA increases the steady-state levels of proenkephalin (PENK) mRNA in the rat hippocampus for at least one year. However, the molecular mechanisms underlying this long-term increase in PENK mRNA levels have not been clearly defined. To determine the possible involvement of the Sp-1 transcription factors in this regulation, electrophoresis mobility-shift assays were used to study the expression of Sp-1 factors in the hippocampus after KA treatment. The results showed that there are long-lasting increases in Sp-1 DNA-binding activity. The Sp-1 DNA-binding complexes were only competed by the non-radioactive Sp-1 element and not by ENKCRE2, AP-1 or CRE elements, indicating the specificity of Sp-1 DNA-binding activity. Since the expression of Sp-1 parallels the time course of long-lasting increase in the expression of PENK mRNA and mossy fiber sprouting after KA treatment, we hypothesize that the increase in Sp-1 activity may be associated with the long-term changes in the plasticity of hippocampal function after KA-induced seizures.
Feng
Z
Z
Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, M.D. F1-01, Research Triangle Park, NC 27709, USA. zfeng@email.msn.com
Chang
R C
RC
Bing
G
G
Hudson
P
P
Tiao
N
N
Jin
L
L
Hong
J S
JS
D000818:Animals; D000906:Antibodies; D001923:Brain Chemistry / Q000235:genetics; D017931:DNA Primers; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000503:physiopathology; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D017931:DNA Primers; D018690:Excitatory Amino Acid Agonists; D016329:Sp1 Transcription Factor; D007608:Kainic Acid