Comorbid rat model of ischemia and β-amyloid toxicity: striatal and cortical degeneration.
Levels of cerebral amyloid, presumably β-amyloid (Abeta), toxicity and the incidence of cortical and subcortical ischemia increases with age. However, little is known about the severe pathological condition and dementia that occur as a result of the comorbid occurrence of this vascular risk factor and Abeta toxicity. Clinical studies have indicated that small ischemic lesions in the striatum are particularly important in generating dementia in combination with minor amyloid lesions. These cognitive deficits are highly likely to be caused by changes in the cortex. In this study, we examined the viability and morphological changes in microglial and neuronal cells, gap junction proteins (connexin43) and neuritic/axonal retraction (Fer Kinase) in the striatum and cerebral cortex using a comorbid rat model of striatal injections of endothelin-1 (ET1) and Abeta toxicity. The results demonstrated ventricular enlargement, striatal atrophy, substantial increases in β-amyloid, ramified microglia and increases in neuritic retraction in the combined models of stroke and Abeta toxicity. Changes in connexin43 occurred equally in both groups of Abeta-treated rats, with and without focal ischemia. Although previous behavioral tests demonstrated impairment in memory and learning, the visual discrimination radial maze task did not show significant difference, suggesting the cognitive impairment in these models is not related to damage to the dorsolateral striatum. These results suggest an insight into the relationship between cortical/striatal atrophy, pathology and functional impairment.
CIHR Group on Vascular Cognitive Impairment, Department of Anatomy and Cell Biology, Western University, London, ON, Canada.
Zareen
Z
Amtul
Shawn N
SN
Whitehead
Robin J
RJ
Keeley
John
J
Bechberger
Alicia L
AL
Fisher
Robert J
RJ
McDonald
Christian C
CC
Naus
David G
DG
Munoz
David F
DF
Cechetto
D016229:Amyloid beta-Peptides; D000686:Amyloidosis / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology; D015897:Comorbidity; D018031:Connexin 43 / Q000378:metabolism; D003342:Corpus Striatum / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D019332:Endothelin-1; D008297:Male; D018782:Maze Learning / Q000502:physiology; D017628:Microglia / Q000473:pathology / Q000502:physiology; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology; D016501:Neurites / Q000473:pathology / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011897:Random Allocation; D017208:Rats, Wistar; D020521:Stroke / Q000473:pathology* / Q000503:physiopathology; D014796:Visual Perception / Q000502:physiology
D016229:Amyloid beta-Peptides; D018031:Connexin 43; D019332:Endothelin-1; C052602:proto-oncogene protein c-fes-fps; D011505:Protein-Tyrosine Kinases
axonal retraction; beta-amyloid; cellular degeneration; infarct; microgliosis