Electrophysiological properties of the noradrenergic neurons of locus coeruleus in an experimental model for Alzheimer's Disease

• Grant number: 17/21750-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): February 02, 2018
• Effective date (End): December 16, 2018
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Luciane Helena Gargaglioni Batalhão
• Grantee: Mariane Cristine Vicente
• Supervisor: Tim Daniel Ostrowski
• Host Institution: Faculdade de Ciências Agrárias e Veterinárias (FCAV). Universidade Estadual Paulista (UNESP). Campus de Jaboticabal. Jaboticabal , SP, Brazil
• Research place: A.T. Still University, Missouri (ATSU), United States
• Associated to the scholarship: 16/04412-0 - Neuroanatomical and functional alterations of the respiratory system during sleep and wakefulness in an experimental model for Alzheimer's Disease, BP.DR

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder often associated with age, whose cognitive and neuropsychiatric manifestations result in progressive disability and eventual incapacitation. More than 70% of patients institutionalized with AD present respiratory dysfunctions and these problems may contribute or lead to cognitive decline. These respiratory impairments probably reflect the alterations of neuronal groups involved in the control of breathing. In addition, recent studies emphasize the possibility that brainstem neurodegeneration in AD precedes the cognitive decline. The brainstem houses major nuclei involved in ventilatory control such as the Locus Coeruleus that is severely affected in Alzheimer's disease (AD).In this way, the project will test the hypothesis that neurons of the Locus coeruleus undergo changes during the progression of Alzheimer's disease. The change in the neurophysiology of LC neurons in different stages of the AD may result in different respiratory symptoms, which precede cognitive decline. As far as we are concerned, there is no data in the literature showing how Locus coeruleus electrophysiological properties alterations are related to respiratory changes in AD progression. The study will be performed in an animal model of sporadic AD, induced by intracerebroventricular streptozotocin (STZ) injections. We will evaluate the intrinsic activity of Locus coeruleus neurons in the progression of AD using the patch clamp technique (14 and 30 days after the icv injection of streptozotocin). Furthermore, we will immunohistochemically document the changes in activation pattern (c-fos staining) of LC neurons to hypercapnia. (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)

VICENTE, MARIANE C.; HUMPHREY, CHUMA M.; GARGAGLIONI, LUCIANE H.; OSTROWSKI, TIM D.. Decreased excitability of locus coeruleus neurons during hypercapnia is exaggerated in the streptozotocin-model of Alzheimer's disease. Experimental Neurology, v. 328, JUN 2020. (17/21750-9)

VICENTE, MARIANE CRISTINE; GARGAGLIONI, LUCIANE HELENA; OSTROWSKI, TIM DANIEL. The CO2/pH Chemosensitivity of Locus Coeruleus Neurons Is Increased in the Streptozotocin-Model of Alzheimer's Disease. FASEB JOURNAL, v. 33, p. 2-pg., 2019-04-01. (17/21750-9)