Serotonin: from top to bottom

Abstract

Serotonin is a monoamine neurotransmitter, which is phylogenetically conserved in a wide range of species from nematodes to humans. In mammals, age-related changes in serotonin systems are known risk factors of age-related diseases, such as diabetes, faecal incontinence and cardiovascular diseases. A decline in serotonin function with aging would be consistent with observations of age-related changes in behaviours, such as sleep, sexual behaviour and mood all of which are linked to serotonergic function. Despite this little is known about serotonin in relation to aging. This review aims to give a comprehensive analysis of the distribution, function and interactions of serotonin in the brain; gastrointestinal tract; skeletal; vascular and immune systems. It also aims to demonstrate how the function of serotonin is linked to aging and disease pathology in these systems. The regulation of serotonin via microRNAs is also discussed, as are possible applications of serotonergic drugs in aging research and age-related diseases. Furthermore, this review demonstrates that serotonin is potentially involved in whole organism aging through its links with multiple organs, the immune system and microRNA regulation. Methods to investigate these links are discussed.

Patterns of selective serotonin reuptake inhibitor use and risk of falls and fractures in community-dwelling elderly people: the Three-City cohort

“…Brainderived serotonin increases osteoblast numbers and decreases bone resorption, therefore increasing bone mass. Conversely, gut-derived serotonin acts to inhibit bone formation and increased circulating serotonin has been associated with lower bone density [45]. Age-related changes in drug absorption, metabolism, and blood-brain barrier permeability may also influence levels of serotonin.…”

Synergistic Effect of Galantamine Carried on a Novel Nano-Drug Delivery System on Induced Lung Disorders in Alzheimer’s Disease

“…[37,38,40,41] 5-OH tryptamine performance as a tissue hormone, neurotransmitter and neuromodulator. [42,43] It is one of the most important neurotransmitters in the central nervous system (CNS) regulating multiple physiological functions such as body temperature, appetite, sleep, mood and pain. [44] Several studies reported that pathological change in 5-HT level have been associated with AD, anxiety and Depression.…”

Serotonin Receptor 6 Mediates Defective Brain Development in Monoamine Oxidase A-deficient Mouse Embryos

“…However, the biological activity of 5-HT is not only regulated by its breakdown but also by its biosynthesis and intracellular handling (33). In 5-HT-synthesizing cells, the transmitter is packed into vesicles with the help of the vesicular monoamine transporter (VMAT) and is secreted if needed.…”

“…The results suggest that developmental apoptosis during early embryonic MAO-A deficiency may be conferred by 5-Htr6. (33) including the mitogen-activated kinase ERK (34 -36), and 5-Htr6 has been suggested to activate ERK1/2 via Fyn kinase (37). ERK1/2 activates a number of downstream targets including Bcl-2 (38) and may therefore constitute a link between 5-HT signaling and the observed developmental defects.…”