• Neurobiology of disease · Dec 2019

    Periodic dietary restriction ameliorates amyloid pathology and cognitive impairment in PDAPP-J20 mice: Potential implication of glial autophagy.

    • Amal Gregosa, Ángeles Vinuesa, María Florencia Todero, Carlos Pomilio, Soledad P Rossi, Melisa Bentivegna, Jessica Presa, Shirley Wenker, Flavia Saravia, and Juan Beauquis.
    • Instituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina; Cátedra de Anatomía e Histología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
    • Neurobiol. Dis. 2019 Dec 1; 132: 104542.

    AbstractDietary restriction promotes cell regeneration and stress resistance in multiple models of human diseases. One of the conditions that could potentially benefit from this strategy is Alzheimer's disease, a chronic, progressive and prevalent neurodegenerative disease. Although there are no effective pharmacological treatments for this pathology, lifestyle interventions could play therapeutic roles. Our objectives were 1) to evaluate the effects of dietary restriction on cognition, hippocampal amyloid deposition, adult neurogenesis and glial reactivity and autophagy in a mouse model of familial Alzheimer's disease, and 2) to analyze the role of glial cells mediating the effects of nutrient restriction in an in vitro model. Therefore, we established a periodic dietary restriction protocol in adult female PDAPP-J20 transgenic mice for 6 weeks. We found that dietary restriction, not involving overall caloric restriction, attenuated cognitive deficits, amyloid pathology and microglial reactivity in transgenic mice when compared with ad libitum-fed transgenic animals. Also, transgenic mice showed an increase in the astroglial positive signal for LC3, an autophagy-associated protein. In parallel, hippocampal adult neurogenesis was decreased in transgenic mice whereas dietary-restricted transgenic mice showed a neurogenic status similar to controls. In vitro experiments showed that nutrient restriction decreased astroglial and, indirectly, microglial NFκB activation in response to amyloid β peptides. Furthermore, nutrient restriction was able to preserve astroglial autophagic flux and to decrease intracellular amyloid after exposure to amyloid β peptides. Our results suggest neuroprotective effects of nutrient restriction in Alzheimer's disease, with modulation of glial activation and autophagy being potentially involved pathways.Copyright © 2019 Elsevier Inc. All rights reserved.

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