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Human fumarylacetoacetate hydrolase (FAH) domain containing protein 1 (FAHD1) is a mitochondrial oxalocatate decarboxylase, the first of its kind identified in eukaryotes. The physiological role of FAHD1 in other eukaryotes is still poorly understood. In C. elegans loss of the FAHD1 ortholog FAHD-1 was reported to impair mitochondrial function, locomotion and egg-laying behavior, yet the underlying mechanisms remained unclear. Using tissue-specific rescue of fahd-1(-) worms, we find that these phenotypic abnormalities are at least in part due to fahd-1's function in neurons. Moreover, we show that egg-laying defects in fahd-1(-) worms can be fully rescued by external dopamine administration and that depletion of fahd-1 expression induces expression of several enzymes involved in serotonin biosynthesis. Together, our results support a role for fahd-1 in modulating serotonin levels and suggest this protein as a novel link between metabolism and neurotransmitter signaling in the nervous system. Finally, we propose a model to explain how a metabolic defect could ultimately lead to marked changes in neuronal signaling.
This article was published in the following journal.
Name: PloS one
Serotonin is a conserved neuromodulator that controls feeding behavior in response to environmental inputs in a wide range of species, including the nematode, Caenorhabditis elegans. To understand the...
The contribution of serotonin and noradrenaline to the modulation of pruriceptive processing was evaluated by administrating antidepressants or noradrenaline reuptake inhibitors. The pretreatment with...
Serotonin (5-hydroxytryptamine; 5-HT) is synthesized mainly within enterochromaffin (EC) cells in the gut, and tryptophan hydroxylase 1 (Tph1) is the rate-limiting enzyme for 5-HT synthesis in EC cell...
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The purpose of this study is to determine if oxaloacetate (OAA) is safe and tolerable at doses of up to 2 grams per day in people with Alzheimer's disease (AD).
Serotonin, 5-hydroxytryptamin (5-HT), plays an important role in regulating the gastrointestinal functions. In this study we will modulate the serotonin system with acute tryptophan deplet...
The investigators wish to investigate neurobiological effects of serotonin 2A receptor modulation in healthy volunteers, contrasting effects of an agonist (psilocybin) and an antagonist (k...
12 normal healthy controls will be treated with 50 mg sertraline once daily for three weeks. Early amplitudes of visually evoked potentials will be examined at day 0, 10 and 21 and statist...
A serotonin receptor subtype found distributed through the CENTRAL NERVOUS SYSTEM where they are involved in neuroendocrine regulation of ACTH secretion. The fact that this serotonin receptor subtype is particularly sensitive to SEROTONIN AGONISTS such as BUSPIRONE suggests its role in the modulation of ANXIETY and DEPRESSION.
A genus of small free-living nematodes. Two species, CAENORHABDITIS ELEGANS and C. briggsae are much used in studies of genetics, development, aging, muscle chemistry, and neuroanatomy.
Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or serotonin agonists.
Proteins from the nematode species CAENORHABDITIS ELEGANS. The proteins from this species are the subject of scientific interest in the area of multicellular organism MORPHOGENESIS.
Drugs that bind to but do not activate SEROTONIN 5-HT4 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN RECEPTOR AGONISTS.
Selective serotonin reuptake inhibitors SSRIs
Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a class of medications that are effective at easing depression symptoms. SNRIs are also sometimes used to treat other conditions such as anxiety and nerve pain. How SNRIs work Serotonin (se...
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...