title: Time-course and regional analyses of the physiopathological changes induced after cerebral injection of an amyloid β fragment in rats.
abstract: Alzheimer's disease (AD) is a neurodegenerative pathology characterized by the presence of senile plaques and neurofibrillary tangles, accompanied by synaptic and neuronal loss. The major component of senile plaques is an amyloid β protein (Aβ) formed by pathological processing of the Aβ precursor protein. We assessed the time-course and regional effects of a single intracerebroventricular injection of aggregated Aβ fragment 25-35 (Aβ(25-35)) in rats. Using a combined biochemical, behavioral, and morphological approach, we analyzed the peptide effects after 1, 2, and 3 weeks in the hippocampus, cortex, amygdala, and hypothalamus. The scrambled Aβ(25-35) peptide was used as negative control. The aggregated forms of Aβ peptides were first characterized using electron microscopy, infrared spectroscopy, and Congo Red staining. Intracerebroventricular injection of Aβ(25-35) decreased body weight, induced short- and long-term memory impairments, increased endocrine stress, cerebral oxidative and cellular stress, neuroinflammation, and neuroprotective reactions, and modified endogenous amyloid processing, with specific time-course and regional responses. Moreover, Aβ(25-35), the presence of which was shown in the different brain structures and over 3 weeks, provoked a rapid glial activation, acetylcholine homeostasis perturbation, and hippocampal morphological alterations. In conclusion, the acute intracerebroventricular Aβ(25-35) injection induced substantial central modifications in rats, highly reminiscent of the human physiopathology, that could contribute to physiological and cognitive deficits observed in AD.
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: Brice
authors.initials: B
authors.lastname: Delair
authors.forename: Stephane
authors.initials: S
authors.lastname: Marchal
authors.forename: Emeline
authors.initials: E
authors.lastname: Keller
authors.forename: Guy
authors.initials: G
authors.lastname: Ixart
authors.forename: Gaelle
authors.initials: G
authors.lastname: Naert
authors.forename: Johann
authors.initials: J
authors.lastname: Meunier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chevallier
authors.forename: Tangui
authors.initials: T
authors.lastname: Maurice
authors.forename: Laurent
authors.initials: L
authors.lastname: Givalois
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000473:pathology; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects; D016874:Neurofibrillary Tangles / Q000187:drug effects* / Q000473:pathology; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D000109:Acetylcholine