Premature bioenergetic and cognitive defects in a rat model of presymptomatic Alzheimer disease

MARTINO ADAMI P; MAGNANI, N; GALEANO, P.; ROTONDARO C; CUELLO C; EVELSON, P; CASTAñO E.M; MORELLI L

Congreso; Reunion Anual SAIB 2013; 2013

lntraneuronal accumulation of amyloid ~ (A~) has been linked to mild cognitive impairment that precedesAlzheimer´s disease (AD) onset. This neuropathological trait was recently mimicked in a novel animal model of AD, the hemizygous (+/-) transgenic (Tg) rats (McGill-R- Thy I-APP). Our aim was to do in Tg(+/-) and controls (WT) a time-course analysis ofthe bioenergetic profile in cognitive areas ofthe brain to assess the impact ofmitochondria functionality on the cognitive performance. We measured A~ levels and performed respirometric andATP synthesis assays with isolated mitochondria from cortex and bippocampus. Cerebral oxidative stress markers were evaluated and behavioral tests performed. Our results showed alterations in respiratory chain functionality and deficient oxidative phosphorylation in 3-month old Tg( +/-) rats as compared to WT. This phenotype was associated to mitochondrial A~ accumulation, higher levels of anxiety and spatial reference memory impairment. However, episodic-like mernory, working memory and spatial leaming were preserved. A clear mitochondrial dysfunction was observed in older Tg( +/-) rats (6 rnonth-old) characterized by lower oxygen consumption rate and increments in reactive oxygen species. Conclusions: bioenergetic deficits may be linked to mitochondrial Aá accumulation and emotional and cognitive alterations at early stage of AD neuropathology