Brain Invaders: Exploring the Impact of Platelet Transmigration on Serotonin Signaling in the Medial Prefrontal Cortex
Recent evidence in immunology has indicated that a peripheral player may be contributing to central serotonergic signaling. Researchers have shown that transmigration of blood platelets across the blood brain barrier (BBB) occurs during times of inflammation in the CNS, but none have suggested whether or not this process impacts central serotonin signaling. This paper addresses current research determining the transmigration of platelets into the CNS under natural conditions and addresses future work to solidify any contribution by platelets to CNS 5-HT signaling. Using immunohistochemistry and confocal imaging we mapped the serotonergic varicosities of the mouse brain and used them in comparison to a swellshark (lacking a peripheral serotonin system) to determine any significant differences. It was observed that the ‘loose-varicosities’ seen in the mouse did not appear to be present in the sharks, indicating that these may actually be transmigrated platelets. In order to determine whether or not platelets that cross the BBB contribute significantly to 5-HT signaling we must first determine an accurate and efficient sensor to extracellular changes of 5-HT. In the presence of Fluoxetine (a serotonin reuptake inhibitor), RTq-PCR was used on a variety of receptors to determine sensitivity. Findings were inconclusive for all but one receptor (ITGB3), showing a significant increase in mRNA transcripts. Our results require further verification of platelets from the microvasculature in the CNS using more definitive labeling techniques, elucidation of additional markers as efficient serotonin sensors, and assessing changes in receptor expression as a function of pharmacological platelet depletion.