Neuroanatomical and functional alterations of the respiratory system during sleep and wakefulness in an experimental model for Alzheimer's Disease

• Grant number: 16/04412-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): November 01, 2016
• Effective date (End): April 15, 2021
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Luciane Helena Gargaglioni Batalhão
• Grantee: Mariane Cristine Vicente
• Host Institution: Faculdade de Ciências Agrárias e Veterinárias (FCAV). Universidade Estadual Paulista (UNESP). Campus de Jaboticabal. Jaboticabal , SP, Brazil
• Associated scholarship(s): 17/21750-9 - Electrophysiological properties of the noradrenergic neurons of locus coeruleus in an experimental model for Alzheimer's Disease, BE.EP.DR

Abstract

The dysfunction of the respiratory system is seen in several neurodegenerative diseases such as Alzheimer's, but how the pathophysiology mechanisms of the disease are related with the respiratory system remain poorly documented. Current clinical criteria for diagnosing AD (Alzheimer's Disease) are mainly focused on cognitive deficits produced by dysfunctions of hippocampal and neocortical areas, while non-cognitive symptoms, such as disorders in the sleep or in the respiratory system are neglected and may precede dementia. Alzheimer's Disease (AD), the most common among neurodegenerative disorders frequently associated with age, is characterized by severe brain degeneration, progressive cognitive decline and presence of hyperphosphorylated Tau neurofibrillary tangles (NFTs) and beta-amyloid plaques (A²). Tau protein is a phosphoprotein that has the function of stabilizing microtubules, its activity is regulated by its phosphorylation kinetics. In brain of patients with AD, Tau protein is found in neurofibrillary tangles (NFTs) formed of hyperphosphorylated Tau, indicating failure in the phosphorylation processes. The neurodegeneration in AD occurs in multiple brain regions including hippocampus, cortex, amygdala, neocortex, subcortical regions and regions involved in central chemosensitivity and maintenance of wakefulness, as locus coeruleus, dorsal raphe and the hypothalamus.Recent studies emphasize the possibility of early involvement of the brainstem in AD, where there are the main regions involved in the control of breathing, so that the dysfunction of the region could precede the dementia stage (cognitive decline) in AD. However, the role of these regions in this disease is not well studied. Thus, this project will test the hypothesis that neurochemical changes in AD promote respiratory problems and these problems may precede cognitive decline. The study will be conducted in an animal model of sporadic AD induced by intracerebroventricular injection of streptozotocin (STZ). In this way, changes in the respiratory system will be evaluated in the progression of AD (18 and 36 days after icv injection of STZ) during sleep and wakefulness. (AU)