Linking COVID-19 and microglia with Parkinson’s disease development

Postdoctoral fellow Dr. Ifeoluwa (Hiphy) Awogbindin (Tremblay Lab; pictured) has received a prestigious Michael Smith Health Research British Columbia (Health Research BC) Research Trainee Award. Jointly funded by the Parkinson’s Society British Columbia, the award will enable Hiphy to investigate the relationship between SARS-CoV-2 infection / COVID-19, microglia, and the development and severity of Parkinson’s disease (PD).

“I hope to demonstrate whether SARS-CoV-2 infection can itself cause PD later in life or if it acts as a first hit that synergizes with subsequent factors to worsen or hasten the progression of PD pathology, all while deciphering the specific outcomes on microglia in the process,” Hiphy says. “Also, as microglial reactivity is linked to both neurotropic viral resolution and PD progression, the study offers a potential framework to evaluate the relevance of microglial treatments.”

Since the onset of the SARS-CoV-2 pandemic in 2019, about a tenth of the world’s population has contracted mild to severe COVID-19 and survived, even after repeated infections. These infections can lead to numerous neurological symptoms – including cognitive impairment, long COVID, and motor impairment – that often persist after an individual clears the virus. There is also evidence that COVID-19 affects microglia, the brain’s immune cells. In the post-mortem brain of individuals who died from COVID-19 complications, researchers have found dysfunctional microglia in the region controlling fine movements, an area that is also impacted in PD. This is particularly concerning as healthy microglia work to keep our brain functioning perfectly; they provide significant support for neuronal connections and functions while removing debris and abnormally formed entities, including the unusual amyloid beta and alpha-synuclein that accumulate in Alzheimer’s disease and PD, respectively.

“I am worried that COVID-19 may soon expand the already exploding number of PD cases, particularly in adults above 50 years old, who constitute about 30 per cent of COVID-19 survivors in Canada,” Hiphy says. “This is the age range where PD is initiated and a prodromal period when the initial non-motor symptoms are often experienced, and we cannot afford to be naïvely unprepared for the next 20 years.” PD globally affects 1 in 100 adults over the age of 60, with the prevalence of the disease having increased 244 per cent between 1990 and 2016.

The Health Research BC award will support Hiphy’s work as a postdoctoral fellow in the Tremblay Lab for three years as he notably contributes to a pilot project funded by Parkinson Canada’s 2022 Research Funding Competition, which was granted to his supervisors Dr. Marie-Ève Tremblay (University of Victoria) and Dr. Therese Di Paolo (Laval University). In this project, he will work with specially engineered models expressing human SARS-CoV-2 receptors (ACE2) infected with low doses of SARS-CoV-2 and a neurotoxin. Hiphy is also contributing to the Tremblay Lab’s research on the outcomes of microglial cellular senescence in a genetic model of Alzheimer’s disease pathology.