The neuroprotective effect of two statins: simvastatin and pravastatin on a streptozotocin-induced model of Alzheimer's disease in rats

J Neural Transm (Vienna). 2011 Nov;118(11):1641-9. doi: 10.1007/s00702-011-0680-z. Epub 2011 Jul 10.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology
  • Animals
  • Disease Models, Animal
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Male
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Pravastatin / pharmacology*
  • Pravastatin / therapeutic use
  • Rats
  • Rats, Wistar
  • Simvastatin / pharmacology*
  • Simvastatin / therapeutic use
  • Streptozocin / administration & dosage*

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Neuroprotective Agents
  • Streptozocin
  • Simvastatin
  • Pravastatin