Open AccessIncreased Amyloid-β Peptide-Induced Memory Deficits in Phospholipid Transfer Protein (PLTP) Gene Knockout Mice
Author(s) -
Catherine Desrumaux,
Amandine Pisoni,
Johann Meunier,
Valérie Deckert,
Anne Athias,
Véronique Perrier,
Vanessa Villard,
Laurent Lagrost,
JeanMichel Verdier,
Tangui Maurice
Publication year - 2012
Publication title -
neuropsychopharmacology
Language(s) - English
Resource type - Journals
eISSN - 1740-634X
pISSN - 0893-133X
DOI - 10.1038/npp.2012.247
Subject(s) - oxidative stress , endocrinology , neuroprotection , medicine , neurodegeneration , phospholipid transfer protein , vitamin e , knockout mouse , amyloid (mycology) , chemistry , antioxidant , phospholipid , biochemistry , disease , inorganic chemistry , receptor , membrane
Oxidative stress is recognized as one of the earliest and most intense pathological processes in Alzheimer's disease (AD), and the antioxidant vitamin E has been shown to efficiently prevent amyloid plaque formation and neurodegeneration. Plasma phospholipid transfer protein (PLTP) has a major role in vitamin E transfers in vivo, and PLTP deficiency in mice is associated with reduced brain vitamin E levels. To determine the impact of PLTP on amyloid pathology in vivo, we analyzed the vulnerability of PLTP-deficient (PLTP-KO) mice to the toxic effects induced by intracerebroventricular injection of oligomeric amyloid-β 25-35 (Aβ 25-35) peptide, a non-transgenic model of AD. Under basal conditions, PLTP-KO mice showed increased cerebral oxidative stress, increased brain Aβ 1-42 levels, and a lower expression of the synaptic function marker synaptophysin, as compared with wild-type mice. This PLTP-KO phenotype was associated with increased memory impairment 1 week after Aβ25-35 peptide injection. Restoration of brain vitamin E levels in PLTP-KO mice through a chronic dietary supplementation prevented Aβ 25-35-induced memory deficits and reduced cerebral oxidative stress and toxicity. We conclude that PLTP, through its ability to deliver vitamin E to the brain, constitutes an endogenous neuroprotective agent. Increasing PLTP activity may offer a new way to develop neuroprotective therapies.