Titolo della tesi: Role and activity of medial prefrontal cortex in the analgesic effect of vortioxetine and in a murine model of depression
The following elaborate examines the involvement of mPFC in pain and depression.
Starting from the analysis of the molecular mechanisms behind the antinociceptive effects of vortioxetine, we found out, using Western Blot analysis on CCI mice tissues, that mice treated with vortioxetine express lower levels of the dimeric form of prokineticin 2 (PK2) in their medial prefrontal cortex (mPFC); vortioxetine is a known antidepressant working on serotoninergic pathways that have been shown to fight neuropathic pain, while prokineticin 2 is a small chemokine involved in many physiological and pathological functions such as neuropathic pain. we also found out that treatment with fluoxetine, a selective serotonin reuptake inhibitor widely used in the treatment of depression, altered neither PK2 expression levels nor pain sensitivity, while venlafaxine, the gold standard for neuropathic pain treatment, acted on neuropathy in a PK2-independent way.
In collaboration with Kobe University, we examined the changes in activity in mPFC in a murine model of depression: mice were injected intracranially with a viral vector expressing the fluorescent calcium sensor GCaMP7c and implanted with an optic fibre in order to measure the fluorescence emitted by the sensor in response to increased neuronal calcium release; after recovery from surgery, half of the mice underwent chronic social defeat stress (SDS) from an aggressive mouse while the other was left untouched; finally all the mice were tested for depressive-like behaviour using social interaction test (SIT) and their mPFC activity was recorded via optic fibre. In mice subjected to SDS, mPFC activity dropped when they were in proximity of the interaction target and was in general comparable to cortical activity while avoiding target; control mice on the other hand showed stronger mPFC activation when close to the target than during avoidance.