title: The neuroprotective effect of two statins: simvastatin and pravastatin on a streptozotocin-induced model of Alzheimer's disease in rats.
abstract: Astrocytes play a fundamental role in glutamate metabolism by regulating the extracellular levels of glutamate and intracellular levels of glutamine. They also participate in antioxidant defenses, due to the synthesis of glutathione, coupled to glutamate metabolism. Although the cause of Alzheimer's disease (AD) remains elusive, some changes in neurochemical parameters, such as glutamate uptake, glutamine synthetase activity and glutathione have been investigated in this disease. A possible neuroprotective effect of two statins, simvastatin and pravastatin (administered p.o.), was evaluated using a model of dementia, based on the intracerebroventricular (ICV) administration of streptozotocin (STZ), and astrocyte parameters were determined. We confirmed a cognitive deficit in rats submitted to ICV-STZ, and a prevention of this deficit by statin administration. Moreover, both statins were able to prevent the decrease in glutathione content and glutamine synthetase activity in this model of AD. Interestingly, simvastatin increased per se glutamate uptake activity, while both statins increased glutamine synthetase activity per se. These results support the idea that these drugs could be effective for the prevention of alterations observed in the STZ dementia model and may contribute to reduce the cognitive impairment and brain damage observed in AD patients.
authors: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-anexo, Porto Alegre, RS, Brazil.
authors: Ana Carolina
authors: AC
authors: Tramontina
authors: Krista Minéia
authors: KM
authors: Wartchow
authors: Letícia
authors: L
authors: Rodrigues
authors: Regina
authors: R
authors: Biasibetti
authors: André
authors: A
authors: Quincozes-Santos
authors: Larissa
authors: L
authors: Bobermin
authors: Francine
authors: F
authors: Tramontina
authors: Carlos-Alberto
authors: CA
authors: Gonçalves
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D013311:Streptozocin / Q000008:administration & dosage*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents; D013311:Streptozocin; D019821:Simvastatin; D017035:Pravastatin