title: Synaptosomal bioenergetic defects are associated with cognitive impairment in a transgenic rat model of early Alzheimer's disease.
abstract: 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.
authors.affiliation: Laboratory of Amyloidosis and Neurodegeneration, Fundación Instituto Leloir-IIBBA-CONICET, Buenos Aires, Argentina.
authors.forename: Pamela V
authors.initials: PV
authors.lastname: Martino Adami
authors.affiliation: Department of Biochemistry and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Celia
authors.initials: C
authors.lastname: Quijano
authors.affiliation: IBIMOL-UBA-CONICET, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Natalia
authors.initials: N
authors.lastname: Magnani
authors.affiliation: Laboratory of Amyloidosis and Neurodegeneration, Fundación Instituto Leloir-IIBBA-CONICET, Buenos Aires, Argentina.|ININCA- UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Pablo
authors.initials: P
authors.lastname: Galeano
authors.affiliation: IBIMOL-UBA-CONICET, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Pablo
authors.initials: P
authors.lastname: Evelson
authors.affiliation: Department of Biochemistry and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Adriana
authors.initials: A
authors.lastname: Cassina
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
authors.forename: Sonia
authors.initials: S
authors.lastname: Do Carmo
authors.affiliation: Laboratory of Protective and Regenerative Therapies of the CNS, Fundación Instituto Leloir-IIBBA-CONICET, Buenos Aires, Argentina.
authors.forename: María C
authors.initials: MC
authors.lastname: Leal
authors.affiliation: Laboratory of Amyloidosis and Neurodegeneration, Fundación Instituto Leloir-IIBBA-CONICET, Buenos Aires, Argentina.
authors.forename: Eduardo M
authors.initials: EM
authors.lastname: Castaño
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
authors.forename: A Claudio
authors.initials: AC
authors.lastname: Cuello
authors.affiliation: Laboratory of Amyloidosis and Neurodegeneration, Fundación Instituto Leloir-IIBBA-CONICET, Buenos Aires, Argentina lmorelli@leloir.org.ar.
authors.forename: Laura
authors.initials: L
authors.lastname: Morelli
mesh_terms: D000544:Alzheimer Disease / Q000178:diet therapy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D060825:Cognitive Dysfunction / Q000209:etiology* / Q000378:metabolism; D004035:Diet Therapy; D004195:Disease Models, Animal; D042967:Electron Transport Complex I / Q000378:metabolism; D004734:Energy Metabolism; D008928:Mitochondria / Q000378:metabolism; D045542:PQQ Cofactor / Q000627:therapeutic use; D051381:Rats; D055647:Rats, Transgenic; D013574:Synaptosomes / Q000378:metabolism*
chemical_list: D045542:PQQ Cofactor; D042967:Electron Transport Complex I
keywords: Amyloid β; early-Alzheimer; hippocampal bioenergetics status; neurodegeneration; synaptosomes