Early mitochondrial dysfunction and behavioral alterations in a new transgenic rat model of presymptomatic Alzheimer disease.

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

Congreso; VIII Meeting of the Society for Free Radical Biology and Medicine, South American Group.; 2013

.Intraneuronal accumulation of arnyloidB (AI3) has been linked to mi Id 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). We performed in Tg(+/-) and control (WT) rats a time-course analysis of the bioenergetic profile in cognitive areas of the brain to assess the impact of mitochondria functionality on behavior. We measured AI3 levels and performed respirometric and ATP synthesis assays with isolated mitochondria from cortex and hippocampus. Oxidative stress markers (TBARS and 8-0HdG) were evaluated. Behavior was tested with Elevated Plus Maze, Open Field, Novel Object Recognition, Y-maze and Morris Water Maze protocols. We found in 3-month-old Tg(+/-) rats as compared to WT alterations in respiratory chain functionality and deficient oxidative phosphorylation associated to mitochondrial AI3 accumulation, higher levels of anxiety and spatial reference memory impairment. However, episodic-like memory, working memory and spatial learning were p eserved. A elear mitochondrial dysfunction was observed in older Tg(+/-) rats characterized bylower oxygen consumption rate and increments in reactive, oxygen species. The phenotype of young Tg(+/-) rats will help to test early therapeutic interventions to modulate mitochondrial AI3 levels, neuropathology and behavior.