Modeling cognitive deficits of Alzheimer's disease with a lesional approach in transgenic mice hAPP/hApoE and non transgénic C57BL/6J

MOREAU, Pierre-Henri (2011) Modeling cognitive deficits of Alzheimer's disease with a lesional approach in transgenic mice hAPP/hApoE and non transgénic C57BL/6J. Thèses de doctorat, Université de Strasbourg.

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Abstract

The sporadic form of Alzheimer’s Disease (AD) concerns 90% of the patients and its major risk factor is the ε4 allele. Cognitive deficits, i.e., spatial disorientation, have been related to the early atrophy of the entorhinal cortex (EC). Other, clinical and histological studies show the role of the basal forebrain cholinergic neurones (BFCNs) in the evolution of cognitive disorders in AD. Traissard and coll. (2007) showed that the combined lesion of the EC and the BFCNs, but not each lesion separately, induces spatial memory deficits which resembles those observed at an advanced stage of AD. My work focused on damaging one or both of these two structures playing a key role in AD in young C57BL/6J non transgenic males and old double transgenic hAPP/hApoE females and evaluates their cognitive and non cognitive deficits. The results show that the combined EC and BFCN lesion affect dramatically spatial memory performances in navigation tasks in C57BL/6J mice, whereas each lesion alone induces only moderate deficits. In addition, the BFCN lesion alone is sufficient to induce massive deficits of object recognition in mice. The profound deleterious effect of the combined lesion of the EC and the BFCN is reproduced in the hAPP/hApoE3 mice. However, the BFCN alone is sufficient to induce the massive deficits in spatial learning and memory performances in hAPP/hApoE4 mice. More generally, the results of this last study suggest that the presence of ApoE4 increases the sensitivity of the mice to brain damages. Our model of combined lesion appears as an interesting tool to study the neurobiological basis of cognitive deficit evolution in AD.

Item Type:	Thesis
Discipline de la thèse / mémoire / rapport :	Sciences du vivant. Neurosciences
Uncontrolled Keywords:	maladie d'Alzheimer ; septum median ; cortex entorhinal ; neurones cholinergiques ; mémoire spatiale ; Mu p75 saporine ; reconnaissance d'objets ; lésions excitotoxiques
Subjects:	CL Classification > DDC Dewey Decimal Classification > 500 Sciences de la nature et mathématiques > 570 Sciences de la vie. Biologie. Biochimie > 572 Biochimie > 572.8 Génétique biochimique Classification Thèses Unistra > Santé > Sciences de la vie, biologie, biochimie > 570 Sciences de la vie. Biologie. Biochimie > 572 Biochimie > 572.8 Génétique biochimique 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
ID Code:	2338
Deposited On:	22 February 2012

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