Astroglial and cognitive effects of chronic cerebral hypoperfusion in the rat.
The permanent occlusion of common carotid arteries (2VO) causes a significant reduction of cerebral blood flow (hypoperfusion) in rats and constitutes a well established experimental model to investigate neuronal damage and cognitive impairment that occurs in human ageing and Alzheimer's disease. In the present study, we evaluated two astroglial proteins--S100B and glial fibrillary acidic protein (GFAP)--in cerebral cortex and hippocampus tissue, glutamate uptake and glutamine synthetase activity in hippocampus tissue, as well as S100B in cerebrospinal fluid. Cognition, as assessed by reference and working spatial memory protocols, was also investigated. Adult male Wistar rats were submitted to 10 weeks of chronic cerebral hypoperfusion by the 2VO method. A significant increase of S100B and GFAP in hippocampus tissue was observed, as well a significant decrease in glutamate uptake. Interestingly, we observed a decrease in S100B in cerebrospinal fluid. As for the cognitive outcome, there was an impairment of both reference and working spatial memory in the water maze; positive correlation between cognitive impairment and glutamate uptake decrease was evidenced in hypoperfused rats. These data support the hypothesis that astrocytes play a crucial role in the mechanisms of experimental neurodegeneration and that hippocampal pathology arising after chronic hypoperfusion gives rise to memory deficits.
Vicente
Evelin
E
Post-graduation Program of Neurocience, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Degerone
Daniel
D
Bohn
Liana
L
Scornavaca
Francisco
F
Pimentel
Alexandre
A
Leite
Marina C
MC
Swarowsky
Alessandra
A
Rodrigues
Letícia
L
Nardin
Patrícia
P
de Almeida
Lucia Maria Vieira
LM
Gottfried
Carmem
C
Souza
Diogo Onofre
DO
Netto
Carlos Alexandre
CA
Gonçalves
Carlos Alberto
CA
D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D016893:Carotid Stenosis / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000378:metabolism; D005911:Gliosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D009414:Nerve Growth Factors / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000032:analysis / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C579158:S100b protein, rat; D018698:Glutamic Acid; D005974:Glutamate-Ammonia Ligase