In vitro evaluation of toxicity in neural cells exposed to ²-amyloid oligomer and the neuroprotective potential of cannabidiol treatment

• Grant number: 23/03166-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2023
• End date: September 15, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Beatriz de Oliveira Monteiro
• Grantee: Vinicius Rodrigues Camilo da Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated scholarship(s): 23/14998-5 - Study of the direct modulation of TrkB receptors by cannabidiol in an in vitro model of Alzheimer's Disease, BE.EP.IC

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease that causes about 70% of dementia cases worldwide. With the advances of technologies in health care and medicine, the life expectancy of the world´s population has increased, but it is noted that this population aging is accompanied by an increase in the number of elderly people with AD. Therefore, considering the worldwide prevalence of AD, and the fact that there is still no effective treatment for this disease, it is essential to understand its pathophysiological mechanisms, to support the search for a more effective treatment for AD. On the pathophysiology of AD it is known that ²-amyloid protein (A²) forms dense extracellular plaques that impair synaptic connections, which leads to cognitive decline and inadequate neuronal functioning. As a drug strategy, cannabidiol (CBD) - non-psychoactive phytocannabinoid - has been investigated for the treatment of AD, because of its neuroprotective effects and anti-inflammatory and antioxidant properties. In vitro models of AD in neural cell cultures have evidenced the fundamental role of glial cells in the clearance of A² protein, which impacts the pathophysiology of AD. The in vitro model with primary neural cells of wild type animals exposed to A² oligomer (OA²) plays an important role in understanding the brain microenvironment, since we can evaluate the response of astrocytes and microglia against the addition of the oligomer, and the modulation of this response by CBD. In this study, the mixed culture of microglia and astrocytes will be used to investigate the hypothesis that a microenvironment more similar to that found in the brain may elicit different responses to degenerative processes related to amyloidogenesis, neurotoxicity and OA²-induced inflammation in glial cells, in which CBD should present therapeutic potential and modulate these responses.