Study of the direct modulation of TrkB receptors by cannabidiol in an in vitro model of Alzheimer's Disease

• Grant number: 23/14998-5
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: January 17, 2024
• End date: March 01, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Beatriz de Oliveira Monteiro
• Grantee: Vinicius Rodrigues Camilo da Silva
• Supervisor: Samia Regiane Lourenco Joca
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: Aarhus University, Denmark
• Associated to the scholarship: 23/03166-9 - In vitro evaluation of toxicity in neural cells exposed to ²-amyloid oligomer and the neuroprotective potential of cannabidiol treatment, BP.IC

Abstract

Alzheimer's disease (AD) is the most common form of neurodegenerative dementia, responsible for 60-70% of cases globally. AD manifests memory and cognitive deficits linked to neuropathological changes like neuronal loss, neurofibrillary tangles, and amyloid-² (A²) plaques formed from amyloid precursor protein (APP) deposits. Microglia, vital immune cells in the brain, can initially clear A² but, when chronically activated, exacerbate inflammation and worsen AD. Astrocytes, another glial cell type, exhibit changes in AD, adopting a pro-inflammatory state, contributing to A² production.Cannabidiol (CBD), a compound from Cannabis sativa, is a promising AD treatment candidate due to its neuroprotective and anti-inflammatory properties. CBD may modulate the endocannabinoid system, impacting CB1 and CB2 receptors, reducing A²-induced neuroinflammation, and mitigating AD-related aspects.Neurotrophins like brain-derived neurotrophic factor (BDNF) are crucial for neuronal health. Reduced BDNF levels in AD contribute to neuronal loss and A² plaque formation. Tropomyosin receptor kinase B (TRKb) receptors, activated by BDNF, play a role in controlling A² progression.This project seeks international collaboration with Dr. Samia Joca's group. We aim to: I) learn how to perform binding technique with biotinilated drugs using HEK cells overexpressing TrkB receptors; ii) investigate CBD effects in TrkB activation in cells exposed to A² oligomers. Upon returning to Brazil, the student will apply this technique to primary microglia and astrocyte cultures exposed to A² oligomers, enhancing ongoing research into AD.