BRAIN BIOENERGETICS AND COGNITIVE PERFORMANCE IN A TRANSGENIC RAT MODEL OF EARLY ALZHEIMER'S DISEASE

MARTINO ADAMI P; QUIJANO C; MAGNANI, N; GALEANO, P.; CASSINA A; LEAL MARIA C.; CUELLO C; MORELLI L

Congreso; 51 Annual Meeting SAIB; 2015

Synaptic bioenergetic deficiencies may be associated with early Alzheimer's disease (AD). To explore this concept we assessed pre-synaptic mitochondrial function in hemizygous (+/-) TgMcGill-R-Thy1-APP rats. The low burden of Aβ and the wide array of behavioral and cognitive impairments described in 6 month-old hemizygous TgMcGill-RThy1-APP rats (Tg(+/-)) support their use to investigate synaptic bioenergetics deficiencies described in subjects with early AD. Here we show that pre-synaptic mitochondria from Tg(+/-) rats evidence a decreased respiratory control ratio and spare respiratory capacity associated with deficits in complex I enzymatic activity. Cognitive impairment was prevented and bioenergetic deficits partially reversed when Tg(+/-) rats were fed a nutritionally complete diet from weaning to 6 month-old supplemented with pyrroloquinoline quinone, a mitochondrial biogenesis stimulator with antioxidant and neuroprotective effects. These results provide evidence that, as described in AD brain and not proven in Tg mice models with AD-like phenotype, the mitochondrial bioenergetic capacity of synaptosomes is not conserved in the Tg(+/-) rats. This animal model may be suitable for understanding the basic biochemical mechanisms involved in early AD.