Artículos de revistas
Synaptosomal bioenergetic defects are associated with cognitive impairment in a transgenic rat model of early Alzheimer's disease
Fecha
2015-11Registro en:
Martino Adami, Pamela Victoria; Quijano, Cecilia; Magnani, Natalia Daniela; Galeano, Pablo; Evelson, Pablo Andres; et al.; Synaptosomal bioenergetic defects are associated with cognitive impairment in a transgenic rat model of early Alzheimer's disease; Sage Publications; Journal Of Cerebral Blood Flow And Metabolism; 37; 1; 11-2015; 69-84
0271-678X
Autor
Martino Adami, Pamela Victoria
Quijano, Cecilia
Magnani, Natalia Daniela
Galeano, Pablo
Evelson, Pablo Andres
Cassina, Adriana
Do Carmo, Sonia
Leal, Maria Celeste
Castaño, Eduardo Miguel
Cuello, Claudio
Morelli, Laura
Resumen
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-R-Thy1-APP rats (Tg(+/-)) 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(+/-) 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(+/-) 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