About this Research Topic
Serotonin (5-hydroxytryptamine, 5-HT) is a multifunctional signaling molecule present in the central nervous system (“central compartment”) and somatic tissues (“peripheral compartment”). Separated by the blood-brain barrier, 5-HT synthesis, degradation and action are independently controlled in each compartment by 5-HT-regulating proteins. In the central 5-HT compartment, 5-HT synthesizing neurons are clustered in discrete regions of the brain stem, projecting their axons into various cortical and subcortical regions of the brain. In the developing brain, 5-HT acts as a neurodevelopmental signal regulating outgrowth of its own neurons and maturation of target regions, while later it modulates brain function and plasticity by acting as a neurotransmitter at the serotonergic synapse. In the peripheral compartment, 5-HT is mainly synthesized in the enterochromaffin cells of the intestinal mucosa. Most of the 5-HT released into portal circulation is accumulated in platelets, and the remaining free plasma 5-HT can exert hormonal actions by activating 5-HT receptors located on various peripheral tissues. Both, central and peripheral serotonin act on multiple organs in order to maintain energy homeostasis by controlling food intake, thermogenesis, and glucose/lipid metabolism.
Based on the involvement of 5-HT in the regulation of developmental processes, as well as on its pleiotropic roles in mental and metabolic functions, serotonin represents a major suspect in many behavioral and metabolic disorders, and pharmacologically based compensation of 5-HT imbalance is already widely used in their treatment. Still, a number of questions remain to be answered. What is the relationship between 5-HT disturbances in the peripheral and central compartments - do they contribute to a disorder synergistically, or do the ones simply represent markers of the others? Does the altered abundance/activity of a certain 5-HT regulating protein, found in a disorder, represent its cause or is it a result of a compensation mechanism? Which molecular substrates, such as altered epigenetic patterns and rare variants of 5HT-related genes, or alternative splicing and RNA-editing of their transcripts, lead to improper expression and function of the 5-HT regulating proteins? An answer to each of these questions represent a cobblestone in a road leading towards a more reliable, early diagnostics and a more successful, individualized therapy.
This Research Topic welcomes Original Research and Review Articles, Short Reports and Mini Reviews dealing with the following subtopics:
• The first subtopic will deal with molecular substrates of developmental disruption of the central and/or peripheral 5-HT homeostasis which can result in an increased vulnerability to behavioral disorders, such as autism, schizophrenia, affective or anxiety disorders.
• The second subtopic will deal with molecular substrates of developmental disruption of the peripheral and/or central 5-HT homeostasis which can result in an increased vulnerability to metabolic disorders, such as obesity, diabetes or metabolic syndrome.
• Since metabolic conditions are becoming recognized as frequent commodities in individuals suffering from mental disorders, the third subsection will place serotonin at the crossroad of mental and metabolic conditions, exploring 5-HT imbalance as a possible common cause.
Keywords: DNA-methylation, histone modifications, 5-hydroxytryptamine, gene polymorphism, RNA expression
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