A chronic physiological rat model of dementia.
We have developed an aging rat model that mimics specific pathology reported in dementia, particularly Alzheimer's disease (AD). The model involves subjecting rats to chronic cerebrovascular insufficiency (CVI) for 1-9 weeks. Gross and sensory-motor function remains normal but spatial memory acquisition and retention are impaired after 1 week and worsens progressively with time. In vivo [31P]NMR spectroscopy evaluation in CVI animals showed membrane phospholipid synthesis increase in the hippocampal-cortex region of affected animals which increases with time. Post-mortem examination revealed that CA1 neurons can express selective damage 1 week after CVI and the number of CA1 neurons thus affected increases in proportion with time. MOreover, there is progressive increase in GFAP hypertrophy and hyperplasia in the hippocampal region during the 9-week observation period. Reduction of microtubule-associated protein 2 and pre-terminal noradrenergic varicosities in the hippocampus-cortex is seen after 9 weeks but not 1 week of CVI. All the above changes have been reported in AD-affected brains. The present CVI model appears as a useful screen in investigating potential therapy for AD as well as increasing understanding of this disorder.
de la Torre
J C
JC
University of Ottawa Faculty of Medicine, Division of Neurosurgery, Ont., Canada.
Fortin
T
T
D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D015140:Dementia, Vascular / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004924:Escape Reaction / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018782:Maze Learning / Q000502:physiology; D011939:Mental Recall / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000473:pathology / Q000502:physiology; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012153:Retention, Psychology / Q000502:physiology; D013570:Synaptic Membranes / Q000473:pathology / Q000502:physiology
D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D010743:Phospholipids