title: Alzheimer's disease related markers, cellular toxicity and behavioral deficits induced six weeks after oligomeric amyloid-β peptide injection in rats.
abstract: Alzheimer's disease (AD) is a neurodegenerative pathology associated with aging characterized by the presence of senile plaques and neurofibrillary tangles that finally result in synaptic and neuronal loss. The major component of senile plaques is an amyloid-β protein (Aβ). Recently, we characterized the effects of a single intracerebroventricular (icv) injection of Aβ fragment (25-35) oligomers (oAβ(25-35)) for up to 3 weeks in rats and established a clear parallel with numerous relevant signs of AD. To clarify the long-term effects of oAβ(25-35) and its potential role in the pathogenesis of AD, we determined its physiological, behavioral, biochemical and morphological impacts 6 weeks after injection in rats. oAβ(25-35) was still present in the brain after 6 weeks. oAβ(25-35) injection did not affect general activity and temperature rhythms after 6 weeks, but decreased body weight, induced short- and long-term memory impairments, increased corticosterone plasma levels, brain oxidative (lipid peroxidation), mitochondrial (caspase-9 levels) and reticulum stress (caspase-12 levels), astroglial and microglial activation. It provoked cholinergic neuron loss and decreased brain-derived neurotrophic factor levels. It induced cell loss in the hippocampic CA subdivisions and decreased hippocampic neurogenesis. Moreover, oAβ(25-35) injection resulted in increased APP expression, Aβ(1-42) generation, and increased Tau phosphorylation. In conclusion, this in vivo study evidenced that the soluble oligomeric forms of short fragments of Aβ, endogenously identified in AD patient brains, not only provoked long-lasting pathological alterations comparable to the human disease, but may also directly contribute to the progressive increase in amyloid load and Tau pathology, involved in the AD physiopathology.
authors.affiliation: Molecular Mechanisms in Neurodegenerative Dementia Laboratory, Inserm U710, Montpellier, France.
authors.forename: Charleine
authors.initials: C
authors.lastname: Zussy
authors.forename: Anthony
authors.initials: A
authors.lastname: Brureau
authors.forename: Emeline
authors.initials: E
authors.lastname: Keller
authors.forename: Stéphane
authors.initials: S
authors.lastname: Marchal
authors.forename: Claire
authors.initials: C
authors.lastname: Blayo
authors.forename: Brice
authors.initials: B
authors.lastname: Delair
authors.forename: Guy
authors.initials: G
authors.lastname: Ixart
authors.forename: Tangui
authors.initials: T
authors.lastname: Maurice
authors.forename: Laurent
authors.initials: L
authors.lastname: Givalois
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000818:Animals; D001522:Behavior, Animal; D001831:Body Temperature; D001835:Body Weight; D001921:Brain / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D057967:Infusions, Intraventricular; D015227:Lipid Peroxidation; D008297:Male; D008568:Memory; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins; D003345:Corticosterone