Platelet-neuron crosstalk: the role of interactions of platelets with brain-specific neuronal glycolipids in the modulation of neuronal functions during neurological disorders

Introduction: Central nervous system (CNS) has one of the highest densities of blood vessels among all other organs. Within the CNS, neuronal cells are located in close connection with endothelial and glial cells around brain capillaries comprising integrated neurovascular units. Platelets constantly circulate in brain blood vessels, can immediately respond to а vascular damage, and are known to be involved in thrombosis and hemostasis. In the intact CNS, platelets do not directly interact with neurons and glial cells due to the impenetrability of the blood-brain barrier (BBB). However, during infection, inflammation, neurodegeneration, trauma, and other pathological conditions, BBB becomes compromised. Both experimental and clinical evidence demonstrates that an increase in BBB permeability takes placeе during many types of neurological disorders including psychiatric diseases and epilepsy. Thus, during pathological conditions platelets could interact with brain glial cells and neurons. We have previously demonstrated that platelets could directly recognize brain-specific gangliosides within neuronal lipid rafts leading to platelet degranulation and release of multiple platelet-derived factors stored in their granules. Platelets could potentially modulate neuronal functions in the affected areas of the brain via the secretion of platelet-derived neurotransmitters such as serotonin or other factors, which is the main goal of our research for this thesis. ; Methods: To investigate the possible effect of platelets on neural electric and gene expression activity in vivo and in vitro, a number of various methods were used that included Electroencephalography (EEG), serotonin (5HT) level in the brain, immunofluorescence, and transcriptomics gene expression analysis. Particularly, EEG was used to analyze general neuronal electric activity in wild-type (WT) mice after pentylenetetrazol (PTZ) injection (acute epilepsy model) for the control group of animals, the group with depleted platelets (~80% of platelet reduction ...