Hippocampal Gαq/₁₁ but not Gαo-coupled receptors are altered in aging

Neuropharmacology. 2013 Jul:70:63-73. doi: 10.1016/j.neuropharm.2013.01.009. Epub 2013 Jan 21.


Normal aging may limit the signaling efficacy of certain GPCRs by disturbing the function of specific Gα-subunits and leading to deficient modulation of intracellular functions that subserve synaptic plasticity, learning and memory. Evidence suggests that Gαq/₁₁ is more sensitive to the effects of aging relative to other Gα-subunits, including Gαo. To test this hypothesis, the functionality of Gαq/₁₁ and Gαo were compared in the hippocampus of young (6 months) and aged (24 months) F344 × BNF₁ hybrid rats assessed for spatial learning ability. Basal GTPγS-binding to Gαq/₁₁ was significantly elevated in aged rats relative to young and but not reliably associated with spatial learning. mAChR stimulation of Gαq/₁₁ with oxotremorine-M produced equivocal GTPγS-binding between age groups although values tended to be lower in the aged hippocampus and were inversely related to basal activity. Downstream Gαq/₁₁ function was measured in hippocampal subregion CA₁ by determining changes in [Ca(2+)]i after mAChR and mGluR (DHPG) stimulation. mAChR-stimulated peak change in [Ca(2+)]i was lower in aged CA₁ relative to young while mGluR-mediated integrated [Ca(2+)]i responses tended to be larger in aged. GPCR modulation of [Ca(2+)]i was observed to depend on intracellular stores to a greater degree in aged than young. In contrast, measures of Gαo-mediated GTPγS-binding were stable across age, including basal, mAChR-, GABABR (baclofen)-stimulated levels. Overall, the data indicate that aging selectively modulates the activity of Gαq/₁₁ within the hippocampus leading to deficient modulation of [Ca(2+)]i following stimulation of mAChRs but these changes are not related to spatial learning.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / metabolism*
  • Aging / psychology*
  • Animals
  • Baclofen / pharmacology
  • CA1 Region, Hippocampal / metabolism
  • Calcium / metabolism
  • Excitatory Amino Acid Agonists / pharmacology
  • GABA-B Receptor Agonists / pharmacology
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism*
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism*
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Learning
  • Male
  • Muscarinic Agonists / pharmacology
  • Oxotremorine / analogs & derivatives
  • Oxotremorine / pharmacology
  • Rats
  • Resorcinols / pharmacology
  • Spatial Behavior


  • Excitatory Amino Acid Agonists
  • GABA-B Receptor Agonists
  • Muscarinic Agonists
  • Resorcinols
  • Oxotremorine
  • 3,5-dihydroxyphenylglycine
  • oxotremorine M
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Baclofen
  • Calcium
  • Glycine