MONOAMINE NUCLEI
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NeurotransmitterA neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotransmitters are released from synaptic vesicles into the synaptic cleft where they are able to interact with neurotransmitter receptors on the target cell. Some neurotransmitters are also stored in large dense core vesicles. The neurotransmitter's effect on the target cell is determined by the receptor it binds to. Many neurotransmitters are synthesized from simple and plentiful precursors such as amino acids, which are readily available and often require a small number of biosynthetic steps for conversion. Neurotransmitters are essential to the function of complex neural systems. The exact number of unique neurotransmitters in humans is unknown, but more than 100 have been identified. Common neurotransmitters include glutamate, GABA, acetylcholine, glycine, dopamine and norepinephrine.
HypothalamusThe hypothalamus (pl.: hypothalami; from Ancient Greek ὑπό (hupó) 'under' and θάλαμος (thálamos) 'chamber') is a small part of the vertebrate brain that contains a number of nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus is located below the thalamus and is part of the limbic system. It forms the basal part of the diencephalon. All vertebrate brains contain a hypothalamus. In humans, it is about the size of an almond. The hypothalamus has the function of regulating certain metabolic processes and other activities of the autonomic nervous system. It synthesizes and secretes certain neurohormones, called releasing hormones or hypothalamic hormones, and these in turn stimulate or inhibit the secretion of hormones from the pituitary gland. The hypothalamus controls body temperature, hunger, important aspects of parenting and maternal attachment behaviours, thirst, fatigue, sleep, circadian rhythms, and is important in certain social behaviors, such as sexual and aggressive behaviors.
Stress (biology)Stress, whether physiological, biological or psychological, is an organism's response to a stressor, such as an environmental condition or change in life circumstances. When stressed by stimuli that alter an organism's environment, multiple systems respond across the body. In humans and most mammals, the autonomic nervous system and hypothalamic-pituitary-adrenal (HPA) axis are the two major systems that respond to stress. Two well-known hormones that humans produce during stressful situations are adrenaline and cortisol. The sympathoadrenal medullary axis (SAM) may activate the fight-or-flight response through the sympathetic nervous system, which dedicates energy to more relevant bodily systems to acute adaptation to stress, while the parasympathetic nervous system returns the body to homeostasis. The second major physiological stress-response center, the HPA axis, regulates the release of cortisol, which influences many bodily functions, such as metabolic, psychological and immunological functions. The SAM and HPA axes are regulated by several brain regions, including the limbic system, prefrontal cortex, amygdala, hypothalamus, and stria terminalis. Through these mechanisms, stress can alter memory functions, reward, immune function, metabolism, and susceptibility to diseases. Disease risk is particularly pertinent to mental illnesses, whereby chronic or severe stress remains a common risk factor for several mental illnesses.
Monoamine neurotransmitterMonoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines are derived from aromatic amino acids like phenylalanine, tyrosine, and tryptophan by the action of aromatic amino acid decarboxylase enzymes. They are deactivated in the body by the enzymes known as monoamine oxidases which clip off the amine group. Monoaminergic systems, i.e., the networks of neurons that use monoamine neurotransmitters, are involved in the regulation of processes such as emotion, arousal, and certain types of memory. It has also been found that monoamine neurotransmitters play an important role in the secretion and production of neurotrophin-3 by astrocytes, a chemical which maintains neuron integrity and provides neurons with trophic support. Drugs used to increase or reduce the effect of monoamine neurotransmitters are used to treat patients with psychiatric and neurological disorders, including depression, anxiety, schizophrenia and Parkinson's disease.
Monoamine transporterMonoamine transporters (MATs) are proteins that function as integral plasma-membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. The three major classes are serotonin transporters (SERTs), dopamine transporters (DATs), and norepinephrine transporters (NETs) and are responsible for the reuptake of their associated amine neurotransmitters (serotonin, dopamine, and norepinephrine). MATs are located just outside the synaptic cleft (peri-synaptically), transporting monoamine transmitter overflow from the synaptic cleft back to the cytoplasm of the pre-synaptic neuron. MAT regulation generally occurs through protein phosphorylation and post-translational modification. Due to their significance in neuronal signaling, MATs are commonly associated with drugs used to treat mental disorders as well as recreational drugs. Compounds targeting MATs range from medications such as the wide variety of tricyclic antidepressants, selective serotonin reuptake inhibitors such as fluoxetine (Prozac) to stimulant medications such as methylphenidate (Ritalin) and amphetamine in its many forms (Adderall, Dexedrine) and derivatives methamphetamine (Desoxyn) and lisdexamfetamine (Vyvanse). Furthermore, drugs such as MDMA ("ecstasy", "molly") and natural alkaloids such as cocaine exert their effects in part by their interaction with MATs, by blocking the transporters from mopping up dopamine, serotonin, and other neurotransmitters from the synapse.
Raphe nucleiThe raphe nuclei (Greek: ῥαφή, "seam") are a moderate-size cluster of nuclei found in the brain stem. They have 5-HT1 receptors which are coupled with Gi/Go-protein-inhibiting adenyl cyclase. They function as autoreceptors in the brain and decrease the release of serotonin. The anxiolytic drug Buspirone acts as partial agonist against these receptors. Selective serotonin reuptake inhibitor (SSRI) antidepressants are believed to act in these nuclei, as well as at their targets.
Monoamine nucleiMonoamine nuclei are clusters of cells that primarily use monoamine neurotransmitters to communicate. The raphe nuclei, ventral tegmental area, and locus coeruleus have been included in texts about monoamine nuclei. These nuclei receive a variety of inputs including from other monoamines, as well as from glutaminergic, GABAergic, and substance p related pathways. The catacholaminergic pathways mainly project upwards into the cortical and limbic regions, power sparse descending axons have been observed in animals models. Both ascending and descending serotonergic pathways project from the raphe nuclei. Raphe nuclei in the obscurus, pallid us, and magnus descend into the brainstem and spinal cord, while the raphe ponds, raphe dorsals, and nucleus centralism superior projected up into the medial forebrain bundle before branching off. Monoamine nuclei have been studied in relation to major depressive disorder, with some abnormalities observed, however MAO-B levels appear to be normal during depression in these regions.
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