A single dose of kainic acid elevates the levels of enkephalins and activator protein-1 transcription factors in the hippocampus for up to 1 year.
Neuronal plasticity plays a very important role in brain adaptations to environmental stimuli, disease, and aging processes. The kainic acid model of temporal lobe epilepsy was used to study the long-term anatomical and biochemical changes in the hippocampus after seizures. Using Northern blot analysis, immunocytochemistry, and Western blot analysis, we have found a long-term elevation of the proconvulsive opioid peptide, enkephalin, in the rat hippocampus. We have also demonstrated that an activator protein-1 transcription factor, the 35-kDa fos-related antigen, can be induced and elevated for at least 1 year after kainate treatment. This study demonstrated that a single systemic injection of kainate produces almost permanent increases in the enkephalin and an activator protein-1 transcription factor, the 35-kDa fos-related antigen, in the rat hippocampus, and it is likely that these two events are closely associated with the molecular mechanisms of induction of long-lasting enhanced seizure susceptibility in the kainate-induced seizure model. The long-term expression of the proenkephalin mRNA and its peptides in the kainate-treated rat hippocampus also suggests an important role in the recurrent seizures of temporal lobe epilepsy.
Bing
G
G
Neuropharmacology Section, Laboratory of Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. bing@niehs.nih.gov
Wilson
B
B
Hudson
P
P
Jin
L
L
Feng
Z
Z
Zhang
W
W
Bing
R
R
Hong
J S
JS
D000818:Animals; D004745:Enkephalins / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D004745:Enkephalins; D018690:Excitatory Amino Acid Agonists; D018808:Transcription Factor AP-1; D007608:Kainic Acid