TY - JOUR
T1 - Molecular indices of neuronal and glial plasticity in the hippocampal formation in a rodent model of age-induced spatial learning impairment
AU - Sugaya, Kiminobu
AU - Chouinard, Michael
AU - Greene, Rhonda
AU - Robbins, Michael
AU - Personett, David
AU - Kent, Caroline
AU - Gallagher, Michela
AU - McKinney, Michael
PY - 1996/5/15
Y1 - 1996/5/15
N2 - 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.
AB - 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.
KW - aging
KW - cognition
KW - immunoblotting
KW - in situ hybridization histochemistry
KW - messenger RNA
KW - spatial learning
UR - http://www.scopus.com/inward/record.url?scp=0029878229&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029878229&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.16-10-03427.1996
DO - 10.1523/jneurosci.16-10-03427.1996
M3 - Article
C2 - 8627377
AN - SCOPUS:0029878229
SN - 0270-6474
VL - 16
SP - 3427
EP - 3443
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 10
ER -