Ethanol withdrawal acts as an age-specific stressor to activate cerebellar P38 kinase

Marianna E. Jung, Xiaohua Ju, James W. Simpkins, Daniel B. Metzger, Liang Jun Yan, Yi Wen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We investigated whether protein kinase P38 plays a role in the brain-aging changes associated with repeated ethanol withdrawal (EW). Ovariectomized young, middle-age and older rats, with or without 17β-estradiol (E2) implantation, received a 90-day ethanol with repeated withdrawal. They were tested for active pP38 expression in cerebellar Purkinje neurons and whole-cerebellar lysates using immunohistochemistry and enzyme-linked immunosorbent assay, respectively. They were also tested for the Rotarod task to determine the behavioral manifestation of cerebellar neuronal stress and for reactive oxygen species (ROS) and mitochondrial protein carbonyls to determine oxidative mechanisms. Middle-age EW rats showed higher levels of pP38-positive Purkinje neurons/cerebellar lysates, which coincided with increased mitochondrial protein oxidation than other diet/age groups. Exacerbated motor deficit due to age-EW combination also began at the middle-age. In comparison, ROS contents peaked in older EW rats. E2 treatment mitigated each of the EW effects to a different extent. Collectively, pP38 may mediate the brain-aging changes associated with pro-oxidant EW at vulnerable ages and in vulnerable neurons in a manner protected by estrogen.

Original languageEnglish
Pages (from-to)2266-2278
Number of pages13
JournalNeurobiology of Aging
Volume32
Issue number12
DOIs
StatePublished - 1 Dec 2011

Fingerprint

Ethanol
Phosphotransferases
Reactive Oxygen Species
Purkinje Cells
Mitochondrial Proteins
Brain
p38 Mitogen-Activated Protein Kinases
Estradiol
Estrogens
Age Groups
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Diet
Neurons

Keywords

  • 17β-estradiol
  • Age
  • Brain-aging-changes
  • Cerebellum
  • Ethanol withdrawal
  • Female rats
  • Mitochondrial protein carbonyls
  • Phosphor-P38 (pP38)
  • Purkinje neurons
  • Reactive oxygen species

Cite this

Jung, Marianna E. ; Ju, Xiaohua ; Simpkins, James W. ; Metzger, Daniel B. ; Yan, Liang Jun ; Wen, Yi. / Ethanol withdrawal acts as an age-specific stressor to activate cerebellar P38 kinase. In: Neurobiology of Aging. 2011 ; Vol. 32, No. 12. pp. 2266-2278.
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Ethanol withdrawal acts as an age-specific stressor to activate cerebellar P38 kinase. / Jung, Marianna E.; Ju, Xiaohua; Simpkins, James W.; Metzger, Daniel B.; Yan, Liang Jun; Wen, Yi.

In: Neurobiology of Aging, Vol. 32, No. 12, 01.12.2011, p. 2266-2278.

Research output: Contribution to journalArticle

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