In vivo regulation of GSK3 phosphorylation by cholinergic and NMDA receptors

Patrizia De Sarno, Gautam N. Bijur, Anna A. Zmijewska, Xiaohua Li, Richard S Jope

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Glycogen synthase kinase-3 (GSK3), which is inhibited by serine-phosphorylation, is involved in the neuropathology of Alzheimer's disease (AD). We tested if the two therapeutic strategies used for AD, inhibition of acetylcholinesterase and of N-methyl-d-aspartate (NMDA) receptors, modulate the phosphorylation state of the two isoforms of GSK3 in mouse brain. Large, rapid increases in the levels of phospho-Ser21-GSK3α and phospho-Ser9-GSK3β occurred in mouse hippocampus, cerebral cortex, and striatum after treatment of mice with the muscarinic agonist pilocarpine or the acetylcholinesterase inhibitor physostigmine. Treatment with memantine, an NMDA receptor antagonist, also increased the serine-phosphorylation of both GSK3 isoforms in mouse brain. Co-administration of physostigmine and memantine increased serine-phosphorylated GSK3 levels equally to that achieved by either agent alone, indicating that the actions of these two drugs converge on overlapping pools of GSK3. Thus, drugs in each class of therapeutic agents used for AD have the common property of increasing the regulatory serine-phosphorylation of GSK3 within common pools of the enzyme.

Original languageEnglish
Pages (from-to)413-422
Number of pages10
JournalNeurobiology of Aging
Volume27
Issue number3
DOIs
StatePublished - Mar 1 2006
Externally publishedYes

Fingerprint

Glycogen Synthase Kinase 3
Cholinergic Agents
Phosphorylation
Serine
Memantine
Alzheimer Disease
Physostigmine
Protein Isoforms
Muscarinic Agonists
Pilocarpine
aspartic acid receptor
Cholinesterase Inhibitors
Brain
Acetylcholinesterase
Pharmaceutical Preparations
Cerebral Cortex
Hippocampus

Keywords

  • Alzheimer's disease
  • Cholinergic
  • GSK3 phosphorylation
  • Memantine
  • Mice
  • Physostigmine
  • Pilocarpine

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)

Cite this

In vivo regulation of GSK3 phosphorylation by cholinergic and NMDA receptors. / De Sarno, Patrizia; Bijur, Gautam N.; Zmijewska, Anna A.; Li, Xiaohua; Jope, Richard S.

In: Neurobiology of Aging, Vol. 27, No. 3, 01.03.2006, p. 413-422.

Research output: Contribution to journalArticle

De Sarno, Patrizia ; Bijur, Gautam N. ; Zmijewska, Anna A. ; Li, Xiaohua ; Jope, Richard S. / In vivo regulation of GSK3 phosphorylation by cholinergic and NMDA receptors. In: Neurobiology of Aging. 2006 ; Vol. 27, No. 3. pp. 413-422.
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