Paul Albert (Canada)

University of Ottawa cellular Molecular Medicine

Author 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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