Alzheimer's disease related markers, cellular toxicity and behavioral deficits induced six weeks after oligomeric amyloid-β peptide injection in rats.

摘要: 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 neuronal loss. The major component an amyloid-β protein (Aβ). Recently, we effects single intracerebroventricular (icv) injection Aβ fragment (25–35) oligomers (oAβ25–35) for up to 3 weeks rats established clear parallel numerous relevant signs AD. To clarify long-term oAβ25–35 its potential role pathogenesis AD, determined physiological, behavioral, biochemical morphological impacts 6 after rats. was still present brain weeks. did not affect general activity temperature rhythms weeks, but decreased body weight, induced short- memory impairments, increased corticosterone plasma levels, oxidative (lipid peroxidation), mitochondrial (caspase-9 levels) reticulum stress (caspase-12 levels), astroglial microglial activation. It provoked cholinergic neuron loss brain-derived neurotrophic factor levels. cell hippocampic CA subdivisions neurogenesis. Moreover, resulted APP expression, Aβ1–42 generation, Tau phosphorylation. In conclusion, this vivo study evidenced soluble oligomeric forms short fragments Aβ, endogenously identified AD patient brains, only long-lasting pathological alterations comparable human disease, may also directly contribute progressive increase amyloid load pathology, involved physiopathology.