Effect of molecular hydrogen treatment in a sporadic model for Alzheimer's disease

• Grant number: 23/15002-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2024
• End date: April 30, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• 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

Abstract

The brain covers a small fraction of the total body mass (~2%) but consumes up to 20% of the oxygen in the body and is a major producer of free radicals/reactive oxygen species (ROS). Due to low levels of antioxidants, auto-oxidation of neurotransmitters and the fact that neurons are rich in polyunsaturated fatty acids, this makes them more prone to lipid peroxidation, making this organ particularly susceptible to oxidative damage. Oxidative stress has been associated with a variety of diseases, including Alzheimer's disease (AD). There is evidence in the literature that oxidative stress modifies the functioning of the main AD biomarkers (²-amyloid membrane proteins and cytoskeletal proteins - tau) and, in this way, becomes a potent promoter of harmful molecular events that are reflected in respiratory, cognitive and molecular symptoms of the disease. Furthermore, oxidative stress is capable of potentiating inflammatory signaling, leading to chronic neuroinflammation and aggravating the molecular and cognitive progression of AD. Therefore, the need for an antioxidant treatment that allows interrupting and/or minimizing the effects of oxidative stress in the intracellular environment during AD is evident. In this scenario, molecular hydrogen (H2) becomes a potential candidate for the treatment and prevention of AD due to its antioxidant, antiapoptotic and anti-inflammatory effects. Furthermore, H2 has several characteristics that make it an interesting molecule for the treatment of AD: 1) it is an inactive molecule and does not interact with biological substances; 2) it has the ability to cross the blood-brain barrier due to its small size; 3) its administration does not cause tolerance; 4) it is easily available and low cost; 5) has no documented serious side effects. Thus, the present study will test the hypothesis that treatment with H2 prevents and/or minimizes respiratory, cognitive, molecular and sleep-wake cycle deficits in a translational experimental model for AD.