Synaptosomal bioenergetic defects are associated with cognitive impairment in a transgenic rat model of early Alzheimer?s disease

MARTINO ADAMI, PAMELA; QUIJANO, CELIA; MAGNANI, NATALIA; GALEANO, PABLO; EVELSON, PABLO; CASSINA, ADRIANA; DO CARMO, SONIA; LEAL, MARÍA CELESTE; CASTAÑO, EDUARDO; CUELLO, CLAUDIO; MORELLI, LAURA

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2017 vol. 37 p. 69 - 84

0271-678X

Synaptic bioenergetic deficiencies may be associated with early Alzheimer?s disease (AD). To explore this concept, we assessed pre-synaptic mitochondrial function in hemizygous (þ/)TgMcGill-R-Thy1-APP rats. The low burden of Ab andthe wide array of behavioral and cognitive impairments described in 6-month-old hemizygous TgMcGill-R-Thy1-APP rats (Tg(þ/)) support their use to investigate synaptic bioenergetics deficiencies described in subjects with early Alzheimer?s disease (AD). In this report, we show that pre-synaptic mitochondria from Tg(þ/) rats evidence a decreased respiratory control ratio and spare respiratory capacity associated with deficits in complex I enzymatic activity. Cognitive impairments were prevented and bioenergetic deficits partially reversed when Tg(þ/) 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(þ/) rats. This animal model may be suitable for understanding the basic biochemical mechanisms involved in early AD.