Molecular indices of neuronal and glial plasticity in the hippocampal formation in a rodent model of age-induced spatial learning impairment

Kiminobu Sugaya, Michael Chouinard, Rhonda Greene, Michael Robbins, David Personett, Caroline Kent, Michela Gallagher, Michael McKinney

Research output: Contribution to journalArticlepeer-review

94 Scopus citations


Spatial learning ability was quantitated in young and aged Long-Evans rats, and molecular markers were assessed in the striatum and hippocampal formation using immunocytochemical, immunoblotting, and in situ hybridization histochemical procedures. The mRNA for β-amyloid precursor protein (βAPP), most likely the transcript encoding the 695-amino acid form of this protein, was elevated in pyramidal and granule cells in the hippocampus of aged rats exhibiting poorer spatial learning. In immunoblots of hippocampal protein extracts, however, the level of βAPP-like immunoreactivity was depressed in the more impaired subjects. Similarly, the level in hippocampus of the mRNA for manganese-dependent superoxide dismutase (Mn-SOD), a marker of oxidative stress, was positively correlated with the degree of behavioral impairment, but immunoblotting revealed that Mn-SOD protein was depressed in the aged hippocampus compared with young. The mRNAs for the neuronal form of nitric oxide synthase and for the astrocyte marker glial fibrillary acidic protein (GFAP) were elevated in the hippocampus in correlation with the extent of learning impairment. In the striatum, the levels of mRNA and protein for several candidate genes, including GFAP, were elevated in parallel with the learning index, but these were age effects. Several hippocampal proteins were unchanged (GFAP) or depressed (βAPP and Mn-SOD) in level, despite elevations in corresponding mRNAs. In the aged cohort, hippocampal GFAP mRNA, Mn-SOD mRNA, and βAPP emerged as predictors of behavioral impairment, suggesting the involvement of these hippocampal systems in age-related cognitive impairment.

Original languageEnglish (US)
Pages (from-to)3427-3443
Number of pages17
JournalJournal of Neuroscience
Issue number10
StatePublished - May 15 1996
Externally publishedYes


  • aging
  • cognition
  • immunoblotting
  • in situ hybridization histochemistry
  • messenger RNA
  • spatial learning

ASJC Scopus subject areas

  • Neuroscience(all)


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