Serotonin and its Receptors in the Human CNS with New Findings - A Mini Review

Abstract

Serotonin (5-hydroxytryptamine, 5-HT) is well known to be closely associated with emotional disorders, such as depression and schizophrenia. The seven main members of 5-HT receptor family including the different subtypes are involved in the functional pathways in the brain and their balance in activity helps to maintain the normal mental stability. As any detrimental changes in the 5-HT system is believed to alter emotion in human, different drugs including serotonin reuptake inhibitors (SSRIs) are nowadays commonly used as anti- depressives. In this review, 5-HT(1A) and 5-HT(2A) receptors and serotonergic positive cells in the human were highlighted in particular. It is hoped that this review will give a map of these major 5-HT receptors and serotonergic neurons in the human CNS to facilitate further deciphering of their functions.

Understanding the role of serotonin in psychiatric diseases

“…Interestingly, if we critically analyze those findings, it is evident that negative results were also present since the beginning but were mostly neglected. Moreover, attempts were made to encompass them in the defect hypothesis through rather complicated explanations, sometimes involving the 5-HT transporter (SERT) and one or more of the 5-HT receptor subtypes (of which there are now 14) discovered and characterized throughout the years 12 – 14 . Similarly, the function of the genes or genetic polymorphisms that have been continually proposed in depression in the last two decades was not always confirmed subsequently and led to less conclusive or inconclusive hypotheses 15 , 16 .…”

Knockout of NPFFR2 Prevents LPS-Induced Depressive-Like Responses in Mice

“…This clinical reality presents a major challenge to the serotonin theory of depression, and as a result, researchers have begun to focus on delineating the non-mutually exclusive actions of monoamines, neurotrophic factors and neurogenesis; empirical observations suggest these factors can modulate severity and remission in depressive disorders [ 10 , 20 ]. Thus, a modern view of MDD pathogenesis is that it probably involves not only a wide spectrum of central serotonergic deficits, ranging from synthesis, catabolism and reuptake to receptor malfunction [ 21 , 22 ], but it also results from complicated interactions between serotonin and other neurotransmitters, neuropeptides and neurotrophins [ 23 , 24 , 25 ].…”

Expression Pattern of 5-HT (Serotonin) Receptors during Normal Development of the Human Spinal Cord and Ganglia and in Fetus with Cervical Spina Bifida

“…Concerning rare studies on humans, the early expression of various transmitters and peptides has been documented in the human CNS during embryonic and fetal developmental stages, and those also included serotonin and its receptors. Many of these transmitters and peptides, including serotonin, declined during normal and abnormal aging as a consequence of cell death or otherwise [ 12 ]. In accordance with our study, it was shown that the serotonergic medullary neurons sent bulbospinal axons to all laminae of the spinal cord and innervated medullary sensory, motor, autonomic and respiratory nuclei.…”

“…The morphogenesis of the human neural tube seems to be influenced by interactions between the neurotransmitters and peptides and neurons already during the early stages of development [ 11 ], including serotonin and its receptors [ 12 ]. The cell bodies of serotonin-expressing cells appear first in the brainstem and mostly project into the spinal cord.…”