Long-term increase of Sp-1 transcription factors in the hippocampus after kainic acid treatment

• Published in: Brain research. Molecular brain research. Vol. 69; no. 1; pp. 144 - 148
• Main Authors: Feng, Zhehui, Chang, Raymond C.C, Bing, Guoying, Hudson, Pearlie, Tiao, Ningyi, Jin, Lei, Hong, Jau-Shyong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 21.05.1999
• Subjects: Animals; Antibodies; AP-1 protein; Brain Chemistry - genetics; CRE protein; Disease Models, Animal; DNA Primers; ENKCRE2 protein; enkephalins; Epilepsy, Temporal Lobe - physiopathology; Excitatory Amino Acid Agonists - pharmacology; Gene Expression - drug effects; Hippocampus; Kainic acid; Kainic Acid - pharmacology; Male; Mossy fiber sprouting; Mossy Fibers, Hippocampal - chemistry; Mossy Fibers, Hippocampal - drug effects; Mossy Fibers, Hippocampal - physiology; Nerve Degeneration - chemically induced; Nerve Degeneration - physiopathology; Protein Binding - physiology; Rats; Rats, Inbred F344; Sp1 protein; Sp1 Transcription Factor - genetics; Sp1 Transcription Factor - immunology; Sp1 Transcription Factor - metabolism; Temporal lobe epilepsy; Transcription factor; KA, kainic acid; PENK, proenkephalin; AP-1, activator protein-1; Mossy fiber sprouting; FRA, Fos-related antigen; DTT, dithiothreitol; CNS, central nervous system; ENK, enkephalin; CRE, cAMP responsive element; Temporal lobe epilepsy; Transcription factor; Kainic acid; Hippocampus
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/S0169-328X(99)00099-6

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.