Assessment of the influence of mild chronic intermittent cold exposure on the core body temperature, cognitive function, and phosphorylated Tau and BAG2 levels in familial and sporadic mouse models of Alzheimer's Disease

• Grant number: 16/01836-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 01, 2016
• End date: October 31, 2017
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Maria Camila Almeida
• Grantee: Robson Cristiano Lillo Vizin
• Supervisor: Andrej A. Romanovsky
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Institution abroad: St. Joseph's Hospital and Medical Center, United States
• Associated to the scholarship: 13/25503-5 - Involvement of TRPM8 channels in thermoregulation of Wistar rats, BP.DR

Abstract

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease, accepted to be caused likely due to genetic and/or environmental factors. Loss of memory is one of the earliest clinical symptoms. AD can be classified into late-onset sporadic (SAD) or early-onset familial (FAD) that corresponds only to 1% of cases, and both are histopathologically characterized by amyloid plaques, composed of beta-amyloid deposition, and neurofibrillary tangles formed from hyperphosphorylation of tau protein. Some important risk factors are suggested to SAD such as diabetes mellitus, aging, anesthesia and hypothermia. In fact, a relation between aging and alteration in core body temperature (Tc) homeostasis, as well as the influence of cold- and anesthesia-induced hypothermia on tau phosphorylation and promoting cognitive deficits has been reported by several studies. Moreover, control of Tc in anesthetized old mice can abolish tau hyperphosphorylation and partially recover memory impairment induced by hypothermia. Recently, the co-chaperone BAG2, a protein described to degrade phosphorylated tau, has allowed a new insight for possible pharmacological targets. In this project, 3xTgAD-mice, an FAD model that shown age-dependent increase in Tc similar to that exhibited by AD patients, and intracerebroventricular-streptozotocin mice, a SAD model, will be used to evaluate the influence of chronic intermittent cold exposure (CIC) on Tc, cognitive function using passive avoidance learning and Barnes maze, and phosphorylated tau and BAG2 protein levels by western blot. The use of these two animal models of AD will allow a better comprehension of the relation between temperature, BAG2 protein levels and DA, which will help drive future studies for the development of new medicines for this disease. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VIZIN, ROBSON CRISTIANO LILLO; HARRIS, GRANT; KUNSTETTER, ANA CANCADO; ALMEIDA, MARIA CAMILA; CARRETTIERO, DANIEL CARNEIRO; ROMANOVSKY, ANDREJ A.. Isoflurane-Induced Hypothermia Does Not Aggravate Memory Impairment in A Sporadic Alzheimer's Disease Rat Model Produced by Intracerebroventricular Streptozotocin. FASEB JOURNAL, v. 33, p. 2-pg., 2019-04-01. (15/02991-0, 16/01836-3, 15/23426-9)