Neurotrophic effects of serum- and glucocorticoid-inducible kinase on adult murine mesencephalic dopamine neurons

Xiqun Chen, Patricia Tagliaferro, Tatyana Kareva, Olga Yarygina, Nikolai Kholodilov, Robert E. Burke

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Mesencephalic dopamine neurons are central to many aspects of human cognition, motivational, and motor behavior, and they are uniquely vulnerable to degenerative neurologic disorders such as Parkinson's disease. There is growing evidence that in the mature brain these neurons not only remain responsive to neurotrophic support, but are dependent on it for viability and function. Little is known of the cellular signaling pathways that mediate this support, although some evidence suggests that protein kinase Akt/PKB may play such a role. Another candidate for such a role is serum-and glucocorticoid-inducible kinase (SGK), a member of the AGC kinase family that is closely related to Akt. We have herein examined the responsiveness of adult mouse dopamine neurons in vivo to overexpression of wild-type and a constitutively active form of SGK by use of viral vector transfer in normal mice and both before and after 6-VOHDA lesion. We find that SGK induces a broad spectrum of neurotrophic effects on these neurons, including induction of neuronal hypertrophy, protection from both neuron death and neurotoxin-induced retrograde axonal degeneration, and axon regeneration. Given the diverse and robust effects of SGK on these neurons, and its abundant expression in them, we suggest that SGK, like closely related Akt, may play a role in their responsiveness to neurotrophic factors and in adult maintenance. It therefore offers a novel target for therapeutic development.

Original languageEnglish
Pages (from-to)11299-11308
Number of pages10
JournalJournal of Neuroscience
Volume32
Issue number33
DOIs
StatePublished - 15 Aug 2012

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