Brain bioenergetics and cognitive performance in a transgenic rat model of early Alzheimer disease

MARTINO ADAMI, PAMELA VICTORIA; QUIJANO, CELIA; MAGNANI, NATALIA; GALEANO, PABLO; CASSINA, ADRIANA; LEAL, MARÍA CELESTE; CUELLO, AUGUSTO CLAUDIO; MORELLI, LAURA

Mar del Plata

Congreso; LI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2015

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Synaptic bioenergetic deficiencies may be associated with early Alzheimer´s disease (AD). To explore this concept we assessed pre-synaptic mitochondrial function in hemizygous (+/-) Tg McGill-R-Thy1-APP rats. The low burden of ABeta and the wide array of behavioral and cognitive impairments described in 6 month-old hemizygous TgMcGill-R-Thy1-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.