The role of ERK1, 2, and 5 in dopamine neuron survival during aging

DOI

10.1016/j.neurobiolaging.2013.09.031

Document Type

Journal Article

Publication Date

3-1-2014

Publication Title

Neurobiology of Aging

Volume

35

Issue

3

First Page

669

Last Page

679

ISSN

1974580

Keywords

Aging, Brain, ERK1/2, ERK5, Fischer-344xBrown Norway F1 hybrids (F344xBN F1), MAP kinases, Striatum, Substantia nigra, Ventral tegmental area

Abstract

Extracellular signal-regulated kinases (ERKs) 1, 2, and 5 have been shown to play distinct roles in proliferation, differentiation, and neuronal viability. In this study, we examined ERK1, 2, and 5 expression and activation in the substantia nigra (SN), striatum (STR), and ventral tegmental area (VTA) during aging. An age-related decrease in phosphorylated ERK5 was observed in the SN and STR, whereas an increase in total ERK1 was observed in all 3 regions. In primary cultures of the SN and VTA, inhibition of ERK5 but not ERK1 and 2 decreased dopamine neuronal viability significantly. These data suggest that ERK5 is essential for the basal survival of SN and VTA dopaminergic neurons. This is the first study to examine ERK1, 2, and 5 expression and activation in the SN, STR, and VTA during aging, and the relative roles of ERK1, 2, and 5 in basal survival of SN and VTA dopaminergic neurons. These data raise the possibility that a decline in ERK5 signaling may play a role in age-related impairments in dopaminergic function. © 2014 Elsevier Inc.

Open Access

Green Accepted

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