Pretreatment with Lovastatin Prevents N-Methyl-D-Aspartate-Induced Neurodegeneration in the Magnocellular Nucleus Basalis and Behavioral Dysfunction

Amalia Dolga, Ivica Granic, Ingrid M. Nijholt, Csaba Nyakas, Eddy A. van der Zee, Paul G. M. Luiten, Ulrich L. M. Eisel*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Besides a beneficial cardiovascular effect, it was recently suggested that statins can also exert neuroprotective actions. In a previous study, we provided in vitro evidence that lovastatin treatment abates excitotoxic cell death in primary cortical neurons. Here, we investigated the neuroprotective effect of lovastatin in an in vivo mouse model. We found that administration of lovastatin (20 mg/kg) significantly protects cholinergic neurons and their cortical projections against N-methyl-D-aspartate (60 nmol)-induced cell death in the magnocellular nucleus basalis, a neuronal cell group that is characteristically affected in Alzheimer's disease. Furthermore, lovastatin-mediated neuroprotection was shown to be dependent on protein kinase B (PKB)/Akt signaling since treatment with the PKB/Akt inhibitor LY294002 blocked the lovastatin-induced neuroprotective effect. The loss of cholinergic neurons after the lesion in the magnocellular nucleus basalis resulted in memory impairment as tested in a passive avoidance paradigm. This was reverted by pre-lesion lovastatin treatment. From these studies we conclude that treatment with lovastatin may provide protection against neuronal injury in excitotoxic conditions associated with neurodegenerative diseases including Alzheimer's disease.
Original languageEnglish
Pages (from-to)327-336
Number of pages10
JournalJournal of alzheimers disease
Volume17
Issue number2
DOIs
Publication statusPublished - 2009

Keywords

  • Cholinergic neurons
  • excitotoxicity
  • lovastatin
  • magnocellular nucleus basalis
  • NMDA
  • passive avoidance test
  • PKB/Akt
  • CORTICAL PROJECTION PATTERNS
  • CA2+ ANTAGONIST NIMODIPINE
  • RETINAL GANGLION-CELLS
  • NITRIC-OXIDE SYNTHASE
  • IN-VIVO
  • BRAIN-INJURY
  • RAT
  • EXPRESSION
  • NEUROPROTECTION
  • PROTEIN

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