Age-related spatial learning impairment is unrelated to spinophilin immunoreactive spine number and protein levels in rat hippocampus

Abstract

Age-related impairments in hippocampus-dependent learning and memory tasks are not associated with a loss of hippocampal neurons, but may be related to alterations in synaptic integrity. Here we used stereological techniques to estimate spine number in hippocampal subfields using immunostaining for the spine-associated protein, spinophilin, as a marker. Quantification of the immunoreactive profiles was performed using the optical disector/fractionator technique. Aging was associated with a modest increase in spine number in the molecular layer of the dentate gyrus and CA1 stratum lacunosum-moleculare. By comparison, spinophilin protein levels in the hippocampus, measured by Western blot analysis, failed to differ as a function of age. Neither the morphological nor the protein level data were correlated with spatial learning ability across individual aged rats. The results extend current evidence on synaptic integrity in the aged brain, indicating that a substantial loss of dendritic spines and spinophilin protein in the hippocampus are unlikely to contribute to agerelated impairment in spatial learning.

Age-Related Memory Impairment Is Associated with Disrupted Multivariate Epigenetic Coordination in the Hippocampus

“…Consistent with previous studies [17], [18], [19], approximately half of the aged subjects displayed deficits relative to young rats, whereas the other half performed within the range of adult controls (Fig. 1A).…”

Loss of precuneus dendritic spines immunopositive for spinophilin is related to cognitive impairment in early Alzheimer's disease

“…Studies of spinophilin were conducted in aging rodents in regions other than associational cortex and produced inconsistent results. For example, Calhoun et al (2008) found no changes in rat hippocampal spinophilin protein with aging, whereas an age-related decrease in spinophilin protein was observed in the striatum (Brown et al, 2005). Our cohort of aged individuals with NCI, MCI, and AD was not optimal for examining an association between age and PreC spinophilin levels, due to a narrow age range (79.0–94.5 years).…”

The ageing cortical synapse: hallmarks and implications for cognitive decline

“…Hippocampal synapse number seems to be preserved in aged rodents in some regions, and decreased in other regions. For example, stereological quantification of spinophilin-immunoreactive spines 79 and electron micrographic analyses of synapses have revealed that there is no age-related synapse loss in hippocampal area CA1 80 . Loss of CA1 synapses is characteristic of AD and, to a lesser extent, mild cognitive impairment in humans 81 .…”