Abstract:
:The integrity of the white matter is critical in regulating efficient neuronal communication and maintaining cognitive function. Damage to brain white matter putatively contributes to age-related cognitive decline. There is a growing interest in animal models from which the mechanistic basis of white matter pathology in aging can be elucidated but to date there has been a lack of systematic behavior and pathology in the same mice. Anatomically widespread, diffuse white matter damage was induced, in 3 different cohorts of C57Bl/6J mice, by chronic hypoperfusion produced by bilateral carotid stenosis. A comprehensive assessment of spatial memory (spatial reference learning and memory; cohort 1) and serial spatial learning and memory (cohort 2) using the water maze, and spatial working memory (cohort 3) using the 8-arm radial arm maze, was conducted. In parallel, a systematic assessment of white matter components (myelin, axon, glia) was conducted using immunohistochemical markers (myelin-associated glycoprotein [MAG], degraded myelin basic protein [dMBP], anti-amyloid precursor protein [APP], anti-ionized calcium-binding adapter molecule [Iba-1]). Ischemic neuronal perikarya damage, assessed using histology (hematoxylin and eosin; H&E), was absent in all shams but was present in some hypoperfused mice (2/11 in cohort 1, 4/14 in cohort 2, and 17/24 in cohort 3). All animals with neuronal perikaryal damage were excluded from further study. Diffuse white matter damage occurred, throughout the brain, in all hypoperfused mice in each cohort and was essentially absent in sham-operated controls. There was a selective impairment in spatial working memory, with all other measures of spatial memory remaining intact, in hypoperfused mice with selective white matter damage. The results demonstrate that diffuse white matter pathology, in the absence of gray matter damage, induces a selective impairment of spatial working memory. This highlights the importance of assessing parallel pathology and behavior in the same mice.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Coltman R,Spain A,Tsenkina Y,Fowler JH,Smith J,Scullion G,Allerhand M,Scott F,Kalaria RN,Ihara M,Daumas S,Deary IJ,Wood E,McCulloch J,Horsburgh Kdoi
10.1016/j.neurobiolaging.2010.09.005subject
Has Abstractpub_date
2011-12-01 00:00:00pages
2324.e7-12issue
12eissn
0197-4580issn
1558-1497pii
S0197-4580(10)00380-5journal_volume
32pub_type
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