Myrthe Van Sprengel

Topic

Utilizing the Diaschisis Model to Investigate the Effects of Stroke on Post-Synaptic Spine Densities

Division of Medical Sciences

Date & location

• Tuesday, September 3, 2024
• 1:00 P.M.
• Medical Sciences Building, Room 160

Examining Committee

Supervisory Committee

• Dr. Craig Brown, Division of Medical Sciences, University of Victoria (Supervisor)
• Dr. Hector Caruncho, Division of Medical Sciences, UVic (Member)
• Dr. Julian Lum, Department of Biochemistry and Microbiology, UVic (Outside Member)

External Examiner

• Dr. Patrick Nahirney, Division of Medical Sciences, UVic

Chair of Oral Examination

• Dr. Juergen Ehlting, Department of Biology, UVic

Abstract

The brain is highly interconnected, and this is crucial to understanding a wide variety of neurological diseases. Identifying changes in brain connectivity circuits that occur in a disease state, like ischemic stroke, helps explain the deficits observed in both the peri-infarct and distally connected regions to the stroke site. This phenomenon is referred to as ‘diaschisis’. Currently, there is a lack of understanding of the structural changes that occur at the neuronal level in both proximal and distal regions that are synaptically connected to the infarct. In this study, 2-photon laser scanning microscopy was employed to examine both acute changes and the long-term changes in dendritic spine densities downstream of a photothrombotic stroke in the primary somatosensory forelimb cortex (S1FL). To do this, adult mice were injected with an anterograde adeno-associated virus (AAV.h1Syn.Cre) which, in conjunction with transgenic mice, labelled post-synaptic neurons with TdTomato and GCaMP6s fluorescent proteins allowing for visualization of neurons directly linked to the infarct site. Results show that dendritic spine density is significantly decreased in the peri-infarct region as well as in the motor cortex (superficial neurons only) after stroke as compared to shams. The secondary somatosensory and contralateral S1FL cortices show no changes in spine density 1-week after stroke. After 6-weeks of recovery (6 weeks after the stroke), spine densities returned to control levels, with the exception of the basilar dendrites on superficial peri-infarct neurons. These findings suggest that not only does stroke cause structural changes to occur in neurons localized in the peri-infarct region, but it also impacts regions heavily reliant on those neurons, supporting the diaschisis model of brain injury. Data suggests that the decreases in spine density 1-week after stroke may be proportionate to the number of synapses they make with neurons in the infarct. In conclusion, these data suggests that changes in dendritic spine densities could play a role in the global dysfunctions observed after stroke and may provide valuable information for therapeutic interventions in the future.