La mutation PS1 : caractérisation phénotypique neurochimique et neuropathologique de souris transgéniques, modèles de la maladie d'Alzheimer

Abstract : In addition to the amyloid cascade hypothesis, predominant in Alzheimer's disease research, other hypotheses have been proposed to explain its pathogenesis. Among those, oxidative stress, mitochondrial dysfunction, and cholinergic alterations were suggested, based on early onset signs contributing in an important way to the physiopathology. Our project studied these factors via phenotypic evaluation in the context of histopathology and neurochemistry in two PS-1 mutations: PS1/A246E transgenic and PS1/I213T knock-in mice, characterized by overexpressed Aß-42 peptide without amyloidosis, together with mild behavioral impairments mimicking early onset Alzheimer's disease. Both mutants showed oxidative damage, as measured by DNA oxidation in regions with increased Aß. Brain regional cartographies of cytochrome oxidase and acetylcholinesterase reflected respectively neuronal metabolism and cholinergic innervation. There was no intrinsic modulation of cytochrome oxidase but rather compensatory phenomena independent of oxidative damage. Cholinergic alterations were important in each mutation, particularly in circuits associated with selective attention and memory.
Complete list of metadatas

https://hal.univ-lorraine.fr/tel-01777271
Contributor : Administrateur Du Ccsd <>
Submitted on : Tuesday, April 24, 2018 - 4:16:13 PM
Last modification on : Thursday, April 26, 2018 - 1:27:56 AM

File

SCD_T_2009_0063_JAZI.pdf
Files produced by the author(s)

Identifiers

  • HAL Id : tel-01777271, version 1

Collections

Citation

Rozat Jazi. La mutation PS1 : caractérisation phénotypique neurochimique et neuropathologique de souris transgéniques, modèles de la maladie d'Alzheimer. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2009. Français. ⟨NNT : 2009NAN10063⟩. ⟨tel-01777271⟩

Share

Metrics

Record views

35

Files downloads

64