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Alzheimer's disease (AD) occurs against a background of cognitive and neurobiological aging. Animal models of normal aging may be used to study the neurobiological structures that are most involved in AD pathology, i.e. hippocampal/cortical systems. For example, spatial learning is dependent upon the integrity of the hippocampus, a structure that is much(More)
Aged Long-Evans rats exhibit deficits in attentional set shifting, an aspect of executive function, relative to adult rats. Impairments in set shifting and spatial learning are uncorrelated in aged rats, indicating a possible dissociation of the effects of ageing in prefrontal versus hippocampal systems. Ionotropic glutamate receptor binding was assessed(More)
Neurons and glia within the hippocampus of aged, spatial learning-impaired Long-Evans rats exhibit uniquely altered gene expression profiles, and we have postulated oxidative stress as the basis for this. To test this hypothesis we quantitated the extent of protein and nucleic acid oxidative damage, evaluated the status of mitochondrial DNA integrity, and(More)
Using in vitro autoradiography, we investigated [3H] alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, [3H]kainate and [3H]N-methyl-D-aspartate binding in two forebrain regions, the hippocampus and striatum, of young (four months of age) and aged (24-25 months of age) Long-Evans rats that had previously been tested for spatial learning ability in the(More)
Maximal phosphoinositide (PI) turnover was examined in the hippocampus of young and aged Long-Evans rats that were behaviorally characterized for spatial learning in the Morris water maze. The type 1 metabotropic glutamate receptor (mGluR) agonist 1S,3R ACPD was used to stimulate PI turnover and to determine the E(MAX) for each rat. Protein levels in(More)
To understand the relationship between amyloid-beta and cognitive decline in Alzheimer's disease, we evaluated cortical and hippocampal function in a transgenic mouse model of amyloid over-expression in Alzheimer's disease, the Tg2576 mouse. Tg2576 mice and their non-transgenic littermates were assessed at both 6 and 14 months of age in a battery of(More)
Tg2576 mice, a transgenic model of amyloid pathology associated with Alzheimer's disease (AD), develop measurable levels of soluble amyloid beta1-40 and 1-42 by 6 months of age and amyloid plaque deposition in cortex, hippocampus and amygdala by 10 months of age. To investigate whether non-hippocampal learning strategies would predominate coincident with(More)
Fractionated partial or whole-brain irradiation (fWBI) is a widely used, effective treatment for primary and metastatic brain tumors, but it also produces radiation-induced brain injury, including cognitive impairment. Radiation-induced neural changes are particularly problematic for elderly brain tumor survivors who also experience age-dependent cognitive(More)
M(1) muscarinic acetylcholine receptors (mAChRs) may represent a viable target for treatment of disorders involving impaired cognitive function. However, a major limitation to testing this hypothesis has been a lack of highly selective ligands for individual mAChR subtypes. We now report the rigorous molecular characterization of a novel compound,(More)
The levels of three different synaptic proteins in the hippocampus of young (6 months of age) and aged (26-27 months of age) Long Evans rats were examined using quantitative Western blotting. An important feature to this study is that prior to the neurobiological analysis, hippocampal function was determined by assessing spatial learning ability in the(More)