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Journal of Neural Transmission

, 118:1641 | Cite as

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

  • Ana Carolina Tramontina
  • Krista Minéia Wartchow
  • Letícia Rodrigues
  • Regina Biasibetti
  • André Quincozes-Santos
  • Larissa Bobermin
  • Francine Tramontina
  • Carlos-Alberto Gonçalves
Dementias - Original Article

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.

Keywords

Astrocyte Glutamate Dementia Statins Streptozotocin 

Notes

Acknowledgments

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), FINEP/Rede IBN 01.06.0842-00 and INCT-National Institute of Science and Technology for Excitotoxicity and Neuroprotection.

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Ana Carolina Tramontina
    • 1
  • Krista Minéia Wartchow
    • 1
  • Letícia Rodrigues
    • 1
  • Regina Biasibetti
    • 1
  • André Quincozes-Santos
    • 1
  • Larissa Bobermin
    • 1
  • Francine Tramontina
    • 2
  • Carlos-Alberto Gonçalves
    • 1
  1. 1.Departamento de BioquímicaInstituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Universidade Estadual do Rio Grande do SulBento GonçalvesBrazil

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