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

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.