Interaction between chronic stress and polymorphism of apolipoprotein E in cognitive and emotional processes in mice: implications for Alzheimer's disease?

KOUTSEFF, Alexis (2011) Interaction between chronic stress and polymorphism of apolipoprotein E in cognitive and emotional processes in mice: implications for Alzheimer's disease? Thèses de doctorat, Université de Strasbourg.

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Abstract

Apolipoprotein E (ApoE) is found in three different forms in human (ApoE2, ApoE3 and ApoE3), and ApoE polymorphism is recognized as one of the most prevalent risk factors for Alzheimer’s disease (AD); ApoE4 increases the risk to develop AD with age, while ApoE2 has protective effects. First, we evaluated the impact of this polymorphism on behavior in adult mice using apoE-KI mouse models. ApoE-Ki mutations had anxiolytic effects in males and anxiogenic effects in females. On the other hand, ApoE-KI mutations did not affect cognitive abilities in our conditions. Afterwards, we analyzed the impact of combined chronic stress and ApoE polymorphism on emotional behavior and cognitive abilities in aged male and female KI mice. Under stress conditions, aged ApoE4 and ApoE2 male mice showed reduced anxiety, while ApoE2 females were more anxious. Moreover both ApoE2 males and females showed reduced susceptibility to despair, whereas ApoE3 females demonstrated increased resignation. Results from cognitive tests show that, under stressed, ApoE4 mutation caused memory deficits which appeared earlier in females. Interestingly, we showed for the first time that stressed ApoE2-KI females displayed improved memory performance at one year old, persisting at more advanced age. Finally, we investigated the combined impact of the ApoE polymorphism, age and sex on hippocampal neurogenesis. We found that young mice carrying the ApoE4 mutation displayed reduced neurogenesis, while young adult ApoE2 females showed improved hippocampal progenitor cell proliferation. Moreover, a surprising protective effect of the ApoE3 genotype was observed in aged females.

Item Type:	Thesis
Discipline de la thèse / mémoire / rapport :	Sciences du vivant. Neurosciences
Uncontrolled Keywords:	apolipoprotéine E ; Alzheimer ; stress chronique ; comportement ; neurogénèse ; cognition ; émotions ; souris transgéniques
Subjects:	UNERA Classification UNERA > ACT Domaine d'activité UNERA > ACT-5 Santé, industrie du médicament, cosmétique UNERA Classification UNERA > DISC Discipline UNERA > DISC-16 Sciences de la vie et de la santé, psychologie CL Classification > DDC Dewey Decimal Classification > 500 Sciences de la nature et mathématiques > 570 Sciences de la vie. Biologie. Biochimie > 572 Biochimie > 572.5 Diverses biomolécules Classification Thèses Unistra > Santé > Sciences de la vie, biologie, biochimie > 570 Sciences de la vie. Biologie. Biochimie > 572 Biochimie > 572.5 Diverses biomolécules
ID Code:	2335
Deposited On:	22 February 2012

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