title: Role of ERK1, 2, and 5 in dopamine neuron survival during aging.
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.
authors.affiliation: Division of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA, USA.
authors.forename: Mayur S
authors.initials: MS
authors.lastname: Parmar
authors.affiliation: Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Juliann D
authors.initials: JD
authors.lastname: Jaumotte
authors.affiliation: Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Wyrostek
authors.affiliation: Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zigmond
authors.affiliation: Division of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA, USA. Electronic address: cavanaughj@duq.edu.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Cavanaugh
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D004298:Dopamine / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism / Q000502:physiology*; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000473:pathology*; D010766:Phosphorylation; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D013378:Substantia Nigra / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D017557:Ventral Tegmental Area / Q000166:cytology / Q000201:enzymology* / Q000473:pathology
chemical_list: D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048054:Mitogen-Activated Protein Kinase 7; D004298:Dopamine
keywords: Aging; Brain; ERK1/2; ERK5; Fischer-344xBrown Norway F1 hybrids (F344xBN F1); MAP kinases; Striatum; Substantia nigra; Ventral tegmental area