Chronic reduction of cerebral blood flow in the adult rat: late-emerging CA1 cell loss and memory dysfunction.
Ten-month-old rats were subjected to permanent bilateral occlusion of both common carotid arteries (2-VO) to chronically but moderately reduce brain blood flow. 2-VO impaired Morris water maze acquisition as soon as 7 days post-surgery. 2-VO also caused a later-appearing impairment on the radial arm maze which did not reach significance until 63 days post-surgery. At 14 dats post-surgery there were no effects of 2-VO on hippocampal CA1 pyramidal cell number or density of glial fibrillary acidic protein (GFAP). Hippocampal choline acetyltransferase activity at 70 days was also unaffected by 2-VO. At 190 days post-surgery, however, the 2-VO rats showed loss of cells and increased GFAP density in CA1. The increased density of hippocampal GFAP correlated with radial arm maze but not Morris water maze impairment. It is suggested that 2-VO causes neuronal dysfunction which can be exacerbated by stress and thereby manifested on aversively motivated tasks such as the water maze. As well, CA1 neurons begin to degenerate after several weeks of the reduced energy availability caused by 2-VO and this impairs memory. Since reduced neuronal energy metabolism is associated with the progressive neurodegeneration that underlies disorders such as Alzheimer's, research should further explore the possibility that the effects of 2-VO may model age-related dementia.
Pappas
B A
BA
Institute of Neuroscience, Carleton University, Ottawa, Ontario, Canada. bpappas@ccs.carleton.ca
de la Torre
J C
JC
Davidson
C M
CM
Keyes
M T
MT
Fortin
T
T
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000502:physiology*; D017536:Carotid Artery, Common / Q000502:physiology; D002560:Cerebrovascular Circulation; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006624:Hippocampus / Q000098:blood supply / Q000473:pathology / Q000502:physiology*; D008297:Male; D018782:Maze Learning; D008568:Memory / Q000502:physiology*; D015999:Multivariate Analysis; D017966:Pyramidal Cells / Q000166:cytology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012039:Regional Blood Flow; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D002795:Choline O-Acetyltransferase