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Volume 17, Number 14, Issue of July 15, 1997 pp. 5407-5415
Copyright ©1997 Society for Neuroscience

Absence of a Persistently Elevated 37 kDa Fos-Related Antigen and AP-1-Like DNA-Binding Activity in the Brains of Kainic Acid-Treated fosB Null Mice

Received March 6, 1997; revised April 23, 1997; accepted May 1, 1997.

Allan Mandelzys¹, Mary Ann Gruda², Rodrigo Bravo², and James I. Morgan¹

¹ Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, and ² Department of Oncology, Bristol Myers-Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000

Chronic stimulation of the nervous system or acute administration of kainic acid results in a persistent increase in AP-1-like DNA-binding activity in the brain. However, the composition and function of these AP-1 complexes remain controversial. By comparing wild-type and fosB-null mice treated with kainic acid, we establish that the complexes comprise JunD in association with an ~37 kDa -FosB species. -FosB was expressed persistently in neurons in many areas of the CNS, even though fosB mRNA only increased transiently. This implies that the 37 kDa protein is very stable. fosB/ mice are predisposed to seizures. Therefore, the chronic expression of -FosB elicited by kainic acid seizures may be indicative of a compensatory/protective role in the pathophysiology of epilepsy.

Key words: -FosB; JunD; chronic Fra; epileptogenesis; protein stability; neurons

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