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

MARTINO ADAMI, PAMELA; MAGNANI, NATALIA; GALEANO, P; ROTONDARO, C; CUELLO, AC; EVELSON, PABLO; CASTAÑO, EDUARDO; MORELLI, LAURA

Ciudad de Buenos Aires

Congreso; Meeting: Molecular mechanisms in cell signaling and gene expression; 2013

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

Intraneuronal accumulation of amyloid β (Aβ) has been linked to mild cognitive impairment that precedes Alzheimer´s disease (AD) onset. This neuropathological trait was recently mimicked in a novel animal model of AD, the hemizygous (+/-) transgenic (Tg) rats (McGill-R-Thy1-APP). Our aim was to do in Tg(+/-) and controls (WT) a time-course analysis of the bioenergetic profile in cognitive areas of the brain to assess the impact of mitochondria functionality on the cognitive performance. We measured Aβ levels and performed respirometric and ATP synthesis assays with isolated mitochondria from cortex and hippocampus. 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 Aβ accumulation, higher levels of anxiety and spatial reference memory impairment. However, episodic-like memory, working memory and spatial learning were preserved. A clear mitochondrial dysfunction was observed in older Tg(+/-) rats (6 month-old) characterized by lower oxygen consumption rate and increments in reactive oxygen species. Conclusions: bioenergetic deficits may be linked to mitochondrial Aâ accumulation and emotional and cognitive alterations at early stage of AD neuropathology