Differential caspase activity in the cortex and striatum with chronic infusion of 3-nitropropionic acid

Journal Reference

Biochem Biophys Res Commun. 2015;465(3):631-7.

Cho KJ¹, Kim GW².

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Department of Neurology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seoul, South Korea.
Department of Neurology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seoul, South Korea. Electronic address: [email protected].

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Abstract

Systemic administration of 3-nitropropionic acid (3-NP) facilitates the development of select striatal lesions, and some reports provide clues about this pathology. In this study, we investigated the relationship between reduced levels of brain-derived neurotrophic factor (BDNF) in lesioned brain regions and caspase activity, as well as involvement of apoptosis signal-regulating kinase 1 (ASK1) in caspase activation. We analyzed apoptotic cell death, BDNF distribution, caspase-3 activity, caspase-6 activity, ASK1 expression level, and active ASK1 in the cortex and striatum. There were different levels and distributions of these factors within each sub-region. Caspase-6 activity was reduced with down-regulation of ASK1 in the cortex. BDNF protein levels did not decrease in the cortex, but there was replenishment of severely reduced BDNF in the striatum. The present study suggests that an increase in ASK1 in the damaged cortex is related to caspase-6 activation and is involved in cortical depletion of BDNF in the striatum. Furthermore, with systemic infusion of 3-NP, differential expression of ASK1 in the cortex and striatum suggests that this kinase may modulate caspase activation and striatal degeneration.

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