title: Partial rescue of memory deficits induced by calorie restriction in a mouse model of tau deposition.
abstract: Calorie restriction (CR) was shown previously to improve cognition and decrease pathology in transgenic mouse models with Alzheimer-like amyloid deposition. In the present study, we investigated the effects of CR on the Tg4510 model of tau deposition. Mice in the calorie restriction group had food intake gradually decreased until they reached an average of 35% body weight reduction. Body weight and food intake were monitored throughout the study. After being on their respective diets for 3 months, all animals were submitted to behavioral testing. Tg4510 mice fed ad libitum showed lower body weight than nontransgenic littermates despite their increased food intake. Additionally, Tg4510 showed increased locomotor activity in the open field regardless of diet. Calorie restricted Tg4510 mice performed significantly better than ad libitum fed mice in the novel object recognition test, suggesting improved short-term memory. CR Tg4510 mice also performed significantly better in contextual fear conditioning than mice fed ad libitum. However, in a modified version of the novelty test that allows for interaction with other mice instead of inanimate objects, CR was not able to rescue the deficit found in Tg4510 mice in this ethologically more salient version of the task. No treatment differences in motor performance or spatial memory were observed in the rotarod or radial arm water maze tests, respectively. Histopathological and biochemical assessments showed no diet-induced changes in total or phospho-tau levels. Moreover, increased activation of both astrocytes and microglia in Tg4510 mice was not rescued by calorie restriction. Taken together, our data suggests that, despite an apparent rescue of associative memory, CR had no consistent effects on pathological outcomes of a mouse model of tau deposition.
authors.affiliation: University of South Florida College of Medicine, Department of Molecular Pharmacology and Physiology, Tampa, FL, United States of America; USF Health Byrd Alzheimer's Institute, Tampa, FL, United States of America.
authors.forename: Milene L
authors.initials: ML
authors.lastname: Brownlow
authors.affiliation: University of South Florida College of Medicine, Department of Molecular Pharmacology and Physiology, Tampa, FL, United States of America; USF Health Byrd Alzheimer's Institute, Tampa, FL, United States of America.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Joly-Amado
authors.affiliation: USF Health Byrd Alzheimer's Institute, Tampa, FL, United States of America.
authors.forename: Sana
authors.initials: S
authors.lastname: Azam
authors.affiliation: USF Health Byrd Alzheimer's Institute, Tampa, FL, United States of America.
authors.forename: Mike
authors.initials: M
authors.lastname: Elza
authors.affiliation: USF Health Byrd Alzheimer's Institute, Tampa, FL, United States of America; University of South Florida College of Pharmacy, Department of Pharmaceutical Sciences, Tampa, FL, United States of America.
authors.forename: Maj-Linda
authors.initials: ML
authors.lastname: Selenica
authors.affiliation: USF Health College of Behavioral & Community Sciences, Tampa, FL, United States of America.
authors.forename: Colleen
authors.initials: C
authors.lastname: Pappas
authors.affiliation: USF Health College of Behavioral & Community Sciences, Tampa, FL, United States of America.
authors.forename: Brent
authors.initials: B
authors.lastname: Small
authors.affiliation: Division of Comparative Medicine, University of South Florida, Tampa, FL, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Engelman
authors.affiliation: University of South Florida College of Medicine, Department of Molecular Pharmacology and Physiology, Tampa, FL, United States of America; USF Health Byrd Alzheimer's Institute, Tampa, FL, United States of America.
authors.forename: Marcia N
authors.initials: MN
authors.lastname: Gordon
authors.affiliation: University of South Florida College of Medicine, Department of Molecular Pharmacology and Physiology, Tampa, FL, United States of America; USF Health Byrd Alzheimer's Institute, Tampa, FL, United States of America. Electronic address: scientist.dave@gmail.com.
authors.forename: Dave
authors.initials: D
authors.lastname: Morgan
mesh_terms: D000544:Alzheimer Disease / Q000178:diet therapy* / Q000523:psychology*; D000818:Animals; D001835:Body Weight; D031204:Caloric Restriction; D003071:Cognition; D004195:Disease Models, Animal; D004435:Eating; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D016896:Treatment Outcome; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins
keywords: Alzheimer's disease; Body weight; Dietary restriction; Food intake; Novel object recognition; Tauopathy