University of Ottawa
Cellular Molecular Medicine-Neuro
RESEARCH INTERESTS Fields: Experimental genetic, stress, and lesion models in behavioral neuroscience, Serotonin axonal plasticity, Optogenetics neuroscience, and MRI scanning Focus: The focus of my research is to understand the dysregulation of neuronal circuitry implicated in depression, depression-related behaviors in different experimental models. Goal: The goal of my research is to promote recovery from depression resistance to Selective Serotonin Reuptake Inhibitors (SSRIs). EDUCATION Ph.D. Cellular Molecular Medicine, Neuroscience program, university of Ottawa, November 2017 Thesis: Altered serotonin regulation in genetic and post-stroke models of anxiety and depression Advisor: Paul R. Albert HONORS and INSTITUTIONAL SERVICES (2019- ) 2021-winter Translational Molecular Medicine course (TMM3009)-Virtual Rotation 2020- Member of CCNP Awards Committee 2020- Member of Faculty Awards Committee, University of Ottawa, Faculty of Medicine 2020- Member of iMED Advisory Committee, University of Ottawa, Faculty of Medicine 2019 Moderator of The Rehab & Recovery Plenary Session on Advances in Cognitive Rehabilitation Therapies, Canadian Stroke Congress, Ottawa, Canada Oct 04, 2019 2019 Expert judging at the 1st Annual Faculty of Medicine Research Day, Ottawa, Canada Sept. 25 2019- VP Academic at the Post-Doctoral Association, Faculty of Medicine, U. of Ottawa 2019- Member of Post-Doctoral Association Award Committee, Faculty of Medicine, U. of Ottawa

Presenter of 1 Presentation

FLUOXETINE-INDUCED 5-HT AXONAL PLASTICITY IN BEHAVIOURAL RECOVERY FOLLOWING UNILATERAL PREFRONTAL CORTICAL ISCHEMIA

Session Type
Oral Presentations
Date
27.10.2021, Wednesday
Session Time
09:50 - 10:30
Room
ORAL PRESENTATIONS 1
Lecture Time
10:00 - 10:10

Abstract

Background and Aims

Research using brain injury models indicates 5-HT axons can regrow and release 5-HT associated with behavioural recovery, after several months. However, the impact of selective serotonin transporter (SERT) inhibitor (SSRI) treatment on 5-HT axonal regeneration has not been tested. Fluoxetine increases synaptic serotonin (5-HT) levels to improve depressive/anxiety symptoms in stroke survivors. We hypothesized that chronic fluoxetine induces a novel 5-HT innervation in mPFC-limbic regions to recover from post-stroke depression (PSD).

Methods

We have reported a mouse model of PSD with no sensorimotor impairments using infusion of endothelin-1 to induce ischemia in the left medial-prefrontal cortex (LmPFC). The PSD mice were tested for depression and anxiety behaviour (1->6 wks post-stroke). Then they were perfused and fixed and brain sections stained for SERT, synaptophysin- gephyrin (inhibitory sites) and -PSD95 to label 5-HT processes and release sites, inhibitory and excitatory synapses. Confocal microscopic images were reconstructed to quantify the volume of SERT+ processes, the density of varicosities and the 5-HT synaptic contacts.

Results

Chronic FLX mediated a full behavioral recovery in the PSD model. After 1-week post-stroke, 5-HT innervation was greatly reduced at the stroke site and the left basolateral amygdala (BLA). At 6 wks post-stroke 5-HT projections, varicosities and 5-HT terminals at excitatory or inhibitory synaptic sites remained reduced. However, fluoxetine induced a complete recovery in the 5-HT circuitry, including in ipsilesional LmPFC and BLA, particularly in contracts with inhibitory (gephyrin-positive) sites.

Conclusions

These findings highlight a novel role for SSRI-induced neuroplasticity of 5-HT projections in behavioral recovery in a model of PSD.

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