RT Journal Article
SR Electronic
T1 Cognitive Deficits, Changes in Synaptic Function, and Brain Pathology in a Mouse Model of Normal Aging
JF eneuro
JO eneuro
FD Society for Neuroscience
SP ENEURO.0047-15.2015
DO 10.1523/ENEURO.0047-15.2015
VO 2
IS 5
A1 Weber, Martin
A1 Wu, Tiffany
A1 Hanson, Jesse E.
A1 Alam, Nazia M.
A1 Solanoy, Hilda
A1 Ngu, Hai
A1 Lauffer, Benjamin E.
A1 Lin, Han H.
A1 Dominguez, Sara L.
A1 Reeder, Jens
A1 Tom, Jennifer
A1 Steiner, Pascal
A1 Foreman, Oded
A1 Prusky, Glen T.
A1 Scearce-Levie, Kimberly
YR 2015
UL http://www.eneuro.org/content/2/5/ENEURO.0047-15.2015.abstract
AB Age is the main risk factor for sporadic Alzheimer’s disease. Yet, cognitive decline in aged rodents has been less well studied, possibly due to concomitant changes in sensory or locomotor function that can complicate cognitive tests. We tested mice that were 3, 11, and 23 months old in cognitive, sensory, and motor measures, and postmortem measures of gliosis and neural activity (c-Fos). Hippocampal synaptic function was also examined. While age-related impairments were detectable in tests of spatial memory, greater age-dependent effects were observed in tests of associative learning [active avoidance (AA)]. Gross visual function was largely normal, but startle responses to acoustic stimuli decreased with increased age, possibly due to hearing impairments. Therefore, a novel AA variant in which light alone served as the conditioning stimuli was used. Age-related deficits were again observed. Mild changes in vision, as measured by optokinetic responses, were detected in 19- versus 4-month-old mice, but these were not correlated to AA performance. Thus, deficits in hearing or vision are unlikely to account for the observed deficits in cognitive measures. Increased gliosis was observed in the hippocampal formation at older ages. Age-related changes in neural function and plasticity were observed with decreased c-Fos in the dentate gyrus, and decreased synaptic strength and paired-pulse facilitation in CA1 slices. This work, which carefully outlines age-dependent impairments in cognitive and synaptic function, c-Fos activity, and gliosis during normal aging in the mouse, suggests robust translational measures that will facilitate further study of the biology of aging.