Explore chapters and articles related to this topic
Diseases of the Nervous System
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
Stress also raises the turnover of serotonin in the brain, although there is no changes in the amount. In the brain of cold-stressed animals, the activity of the rate-limiting enzyme in serotonin biosynthesis, tryptophan 5-hydroxylase is increased. Electric shock increases serotonin synthesis in the rat brain. The turnover of serotonin in the brain is less in isolated animals than in group-living animals exposed to more stress. These findings show that stress-induced acceleration of nonepinephrine turnover is linked with defensive-aggressive functions, and that increased turnover of serotonin is associated with fear.
Summation of Basic Endocrine Data
Published in George H. Gass, Harold M. Kaplan, Handbook of Endocrinology, 2020
Melatonin is derived from tryptophan through a cascade of stages. The tryptophan is converted enzymatically (tryptophan hydroxylase) to 5-hydroxytryptophan, which changes to 5-hydroxytryptamine (serotonin) by aromatic l-amino decarboxylase. Serotonin N-acteyl transferase then changes serotonin to N-acetyl serotonin plus hydroxyindole-O-methyl transferase. The transfer of a methyl group from S-adenosylmethionine to the 5-hydroxyl of N-acetyl serotonin yields melatonin.
Pineal Function
Published in Nate F. Cardarelli, The Thymus in Health and Senescence, 2019
Acetyl Co-A serves as the acetyl donor in the conversion by NAT of serotonin to acetylserotonin.173 Serotonin is synthesized from tryptophan in a reaction catalyzed by tryptophan-5-hydroxylase.174 The enzyme is found in high quantities in the pineal gland, portions of the brain stem, and in human carcinoid tumor. Acute lithium administration causes an increase in this enzyme, and thus enhanced serotonin production in the pineal,175whereas chronic administration suppresses NAT activity.156
Mood disorders and hormonal status across women’s life: a narrative review
Published in Gynecological Endocrinology, 2022
Alice Antonelli, Andrea Giannini, Peter Chedraui, Patrizia Monteleone, Marta Caretto, Alessandro D. Genazzani, Paolo Mannella, Tommaso Simoncini, Andrea R. Genazzani
Serotonin is an important neurotransmitter mostly involved in depressive disorders [31]. The maximum concentrations of this neurotransmitter, derived from tryptophan, can be found in the medial raphe nuclei of the midbrain with fibers extending to the frontal cortex, thalamus, striatum, amygdala, hypothalamus, and hippocampus. Many factors may influence serotonergic neurotransmission: hormone production through the tryptophan hydroxylase, receptor variants, binding, and affinity and, last but not least sex hormones [32]. Regarding estrogens, they are able to modulate synthesis, degradation and binding of serotonin to its receptor [33, 34]. This has been demonstrated by an increase in tryptophan hydroxylase mRNA in brain areas associated with mood control [35, 36]. These effects seem to disappear when the hormone is chronically administered [37]. Progesterone also appears to be involved in serotonergic transmission but, in this case, it regulates serotonin-related genes and proteins [34]. Furthermore, what happens for estrogen in chronic therapy also occurs for progesterone, thus reducing the expression of serotonergic receptors [38]. Selective Serotonin Reuptake Inhibitors (SSRI)-based antidepressant therapy is affected by the effects of estrogen and progesterone, which has been shown in macaque studies and subsequently observed in humans. In the latter case, when women are subjected to SSRIs, the hormone-related effect is especially evident when comparing women of fertile age with menopausal ones. The decreased benefit of antidepressant therapy is most probably due to a deficient hormonal state [39, 40].
Emerging therapies in the management of Irritable Bowel Syndrome (IBS)
Published in Expert Opinion on Emerging Drugs, 2022
Jill E. Elwing, Hadi Atassi, Benjamin D. Rogers, Gregory S. Sayuk
For several decades now, the serotonergic system has been a key target in the development of novel IBS therapies. More than 90% of the serotonin (5-HT) present in humans can be localized to the GI tract, the vast majority contained within the epithelial enterochromaffin cells, and a small percentage within the enteric nervous system. 5-HT is known to have an important role in GI motility, secretion, and visceral sensitivity, and accordingly is regarded to be a key neurotransmitter in IBS pathophysiology [64]. Seven distinct subtypes of 5-HT receptors have been identified in the brain and gut, with 5-HT3 receptors localized to the intestinal nerve plexuses, including sympathetic and parasympathetic nerves [65]. As previously noted, the 5-HT3 antagonist alosetron is FDA-approved for the treatment of IBS with diarrhea. Further, 5-HT4 agonists have been developed for constipation-predominant patients and tegaserod has been developed and approved for the management of IBS-D. Tryptophan hydroxylase is responsible for the initial -OH addition (hydroxylation) to the 5 position to form the amino acid 5-hydroxytryptophan (5-HTP), the rate-limiting step in the synthesis of serotonin. Orally bioavailable, small-molecule tryptophan 5–hydroxylase (TPH) inhibitors, resulting in reductions in serotonin synthesis in the intestine, are being explored for IBS treatment [66].
LIM kinase inhibitor T56-LIMKi protects mouse brain from photothrombotic stroke
Published in Brain Injury, 2021
Svetlana V. Demyanenko, Anatoly Uzdensky
Protein kinase DYRK1A regulates proliferation, differentiation and apoptosis in the developing brain (47). In the adult brain, its overexpression leads to disruption of various signaling pathways, loss of neurons, aging and development of various neurodegenerative diseases (22). Under oxidative stress, DYRK1A stimulates neuronal apoptosis (48). Its inhibitor harmine was shown to reduce cerebral edema, inflammation, and apoptosis of neurons caused by ischemic or traumatic brain injury (49,50). However, in the present experiments harmine was ineffective. Tryptophan hydroxylase mediates serotonin biosynthesis in serotoninergic neurons. Its inhibition by PCPA also did not protect the mouse brain from the PTS consequences. Possibly, these neurochemical processes were not involved in the protection of the peri-infarct region cells after PTS.