Dynamic regulation of c-Jun N-terminal kinase activity in mouse brain by environmental stimuli

Xiao Xu, Jacob Raber, Daseng Yang, Bing Su, Lennart Mucke

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

Activation of the recently identified c-Jun N-terminal kinases (JNKs) typically results in programmed cell death (apoptosis) in neurons and other cell types grown in culture. However, the effects of JNK activation in the central nervous system in vivo are unknown. At baseline, JNK activity in mice was on average 17-fold higher in brain than in peripheral organs, whereas JNK protein levels were similar. In brain, JNK was expressed primarily in neurons. Restraining mice or allowing them to explore a novel environment rapidly increased JNK activity 3- to 15-fold in various brain regions, but these manipulations did not increase brain activity of the extracellular signal-regulated kinase. Because noninvasive environmental stimuli that do not induce neurodegeneration elicited prominent increases in JNK activity in the brain, we conclude that acute activation of the JNK cascade in central nervous system neurons does not induce neuronal apoptosis in vivo. In contrast, the high baseline activity of JNK in the brain and the activation of the JNK cascade by environmental stimuli suggest that this kinase may play an important physiological role in neuronal function.

Original languageEnglish (US)
Pages (from-to)12655-12660
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number23
DOIs
StatePublished - Nov 11 1997

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