Dynamic Regulation of c-Jun N-Terminal Kinase Activity in Mouse Brain by Environmental Stimuli

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 94; no. 23; pp. 12655 - 12660
• Main Authors: Xu, Xiao, Raber, Jacob, Yang, Daseng, Su, Bing, Mucke, Lennart
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 11.11.1997; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences of the USA
• Subjects: Amygdala; Animals; Antibodies; Biological Sciences; Biology; Brain; Brain - physiology; Brain stem; Calcium-Calmodulin-Dependent Protein Kinases - physiology; Central nervous system; Environment; Enzyme Activation; Hippocampus; Hypothalamus; JNK Mitogen-Activated Protein Kinases; Male; Mice; Mitogen-Activated Protein Kinases; Neocortex; Nervous system; Neurology; Neurons; Rodents
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.23.12655

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.