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Sunday, 15 December 2013

The Effects of Hormone Serotonin (5)

Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter derived from tryptophan,  primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS). In Gut, serotonin regulates intestinal movements, in CNS, it regulates mood, appetite, sleep, memory and learning, etc.
41. Serotonin and irritable bowel syndrome with diarrhea
In a biopsy specimens evaluation to assess the inflammation, enterochromaffin cell numbers, 5-HT content, and messenger RNA (mRNA) levels for the synthetic enzyme, tryptophan hydroxylase 1, and the serotonin transporter (SERT)  by quantitative real-time reverse-transcription polymerase chain reaction, indicated that the role of 5-HT signaling in IBS in children and argue against such a role in FD(41).


42. 5-HT(1A) receptors and lower urinary tract function and 'fight-or-flight' conditions
In the study to examine the role of 5-HT(1A) receptors in control of lower urinary tract function in cats,  using 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) as agonists and WAY100635 and LY206130 as antagonists, found that  5-HT(1A) receptor stimulation is inhibitory to bladder function in cats, especially under conditions where the bladder is hyperactive due to irritation. Furthermore, these bladder-inhibitory effects are the exact opposite of the bladder-excitatory effects of 8-OH-DPAT reported in rats. 5-HT(1A) receptor stimulation increases EUS motoneuron activity when driven by nociceptive bladder afferent inputs but not when driven by non-nociceptive afferent inputs. In summary, 5-HT(1A) receptor agonists facilitate a nociceptor-driven spinal reflex (sphincter activity) but inhibit a nociceptor-driven supraspinal reflex (micturition). This pattern of activity would facilitate urine storage and may be important under 'fight-or-flight' conditions when serotonergic activity is high(42).

43. Neuronal serotonin regulates growth of the intestinal mucosa
5-HT promotes growth and turnover of the intestinal mucosal epithelium. Surprisingly, these processes appear to be mediated by neuronal, rather than mucosal, 5-HT. The 5-HT(2A) receptor activates cholinergic neurons, which provide a muscarinic innervation to epithelial effectors, according to teh study by College of Physicians and Surgeons, Columbia University(43)

44. Serotonin and reproduction
Serotonin, a biogenic amine, is present in significant amounts in many structures of the CNS. It is involved in regulation of a wide variety of physiological functions, such as sensory and motor functions, memory, mood, and secretion of hormones including reproductive hormones. In the study of oral administration to female CD rats (20/group) at doses of 0, 3, 10, or 30 mg/kg to evaluate effects on mating, fertility, litter size, live birth index (100 x total liveborn progeny/litter size), progeny survival, and weight gain of each litter, found that on postpartum day 8, progeny in the control, 30 mg/kg and 30 mg/kg recovery groups were removed from dams for 4 h. Progeny were weighed as litters, returned to the dams for a 1-h nursing period, and then weighed again to provide an indication of milk intake. Mating and fertility, using the present study design, were not affected by treatment with amesergide. No effects were observed on litter size, live birth index, or progeny survival. In contrast, treatment with amesergide throughout gestation and lactation produced a significant dose-related depression in progeny body weight gains(44).

45. Serotonin and aging
In the study to assess Serotonin (5-HT) neuron and neurotransmitter loss in normal aging and neuropsychiatric diseases of late life and its contribution to behavioral changes commonly observed in the elderly population, found that there is also increasing evidence that a combination of disturbances in cholinergic and serotonergic function may play a role in cognitive impairment in Alzheimer's disease (AD), with serotonergic dysfunction potentially responsible for a significant portion of the behavioral aspects of the disease. This implication of the 5-HT system in aging and age-related cognitive and mood disorders rests in large part on post mortem studies and animal models, which are limited in their capacity to predict dynamic human biochemical-behavior relationships or to accurately model the living human brain. Initial applications of functional brain imaging with positron emission tomography (PET) in the in vivo study of the brain in aging depression, and dementia focused on characterizing alterations in physiological measurements of cerebral metabolism and perfusion. However, recent advances in PET radiochemistry, instrumentation, and image processing have paved the way for noninvasive means to test specific hypotheses regarding the direct involvement of 5-HT neurons in the behavioral features of aging and to define and monitor therapeutic regimens for neuropsychiatric conditions of late life(45).

46. The role of serotonin in the regulation of bone metabolism

In the brain, brain derived serotonin regulates bone mass through sympathetic nervous system. In addition, inhibition of GDS biosynthesis can treat osteoporosis in ovariectomized rodents by increasing bone formation. The emerging evidence has suggested that inhibiting GDS biosynthesis could become a new anabolic treatment for osteoporosis in humans, according to thye study by Department of Genetics and Development, Columbia University(46).

47. N-acetyl serotonin and neuroprotectants for retinas
N-acetylserotonin (NAS) is synthesized from serotonin by arylalkylamine N-acetyltransferase (AANAT), which is predominantly expressed in the pineal gland and retina. Researchers at the  Emory University School of Medicine, found that he compound N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3-carboxamide (HIOC) selectively activates TrkB receptor with greater potency than NAS. It potently protects retinas from light-induced retinal degeneration (LIRD), which is tightly coupled with pronounced TrkB activation in retinas. Pharmacokinetic studies demonstrate that this compound is stable in serum and liver microsomes. It can pass the blood-brain barrier and blood-retinal barrier. Hence, HIOC is a good lead compound for further drug development for treating retinal degenerative diseases(47).

48. Serotonin and inflammatory pain
In the study to investigate the reverse transcriptase polymerase chain reaction (RT-PCR) technique used to examine the changes of the expression of 5-hydroxytryptamine (5-HT) receptors in the rat lumbar dorsal root ganglion (DRG) following subcutaneous bee venom (BV) injection into the plantar surface of the unilateral hindpaw, showed that the different sets of 5-HT receptor subtypes work at different stages of the inflammatory pain induced by subcutaneous BV injection(48).

49. Serotonin and life span
In the study to develop a new quantitative method to analyze Caenorhabditis elegans behavioral states, found that the proportion of time spent in each state is modulated by past nutritional experiences of the animal. This two-state behavior is regulated through serotonin as well as insulin and TGF-beta signaling pathways. Biogenic amines signaling could allow the worm to adapt to fast changes in the environment when peptide transcriptional pathways may mediate slower adaptive changes(49).

50. Fetal serotonin signaling: setting pathways for early childhood development and behavior
Finely tuning levels of the key neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) during early life is essential for brain development and setting pathways for health and disorder across the early life span. Understanding the impact of early changes in serotonergic programming offers critical insights that might explain patterns of individual differences in developmental risk and resilience, according to the study by  Child and Family Research Institute(50).

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Sources
(41) http://www.ncbi.nlm.nih.gov/pubmed/20303355
(42) http://www.ncbi.nlm.nih.gov/pubmed/12137933
(43) http://www.ncbi.nlm.nih.gov/pubmed/22609381
(44) http://www.ncbi.nlm.nih.gov/pubmed/8118111
(45) http://www.ncbi.nlm.nih.gov/pubmed/9571651
(46) http://www.ncbi.nlm.nih.gov/pubmed/21123937
(47) http://www.ncbi.nlm.nih.gov/pubmed/22331903
(48) http://www.ncbi.nlm.nih.gov/pubmed/15664120
(49) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762077/
(50) http://www.ncbi.nlm.nih.gov/pubmed/22794534