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Homeostasis of Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
Common to all monoaminergic neurotransmitters are reuptake mechanisms in which the released neurotransmitter is taken back into the secreting cell by membrane-embedded transporters. Reuptake fulfills two important functions: (1) guarding against neuronal overstimulation through the removal of the released messenger from the synaptic cleft, resulting in the rapid termination of its actions, and (2) enabling energy conservation by recycling and reutilizing existing molecules rather than producing energy-costly new transmitters [37]. Once the released molecule is brought back into the secreting cell, the next step is its repackaging into storage/secretory vesicles (Figure 1.6). Repackaging is accomplished by two vesicular monoamine transporters, VMAT1 and VMAT2, whose main roles are to (1) protect the transmitter from degradation by intracellular MAO, (2) maintain an adequate intraneuronal storage/secretory capacity to ensure prompt responses to subsequent stimuli, and (3) enable a regulated release of the neurotransmitter from storage vesicles rather than its unregulated release by diffusion [38].
Pharmacotherapy of Neurochemical Imbalances
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Rupali Patil, Aman Upaganlawar, Suvarna Ingale
After the execution of the action, neurotransmitter is inactivated by different mechanisms such as diffusion out of synaptic cleft, inactivation or disintegration by specific enzymes, engulfment by astrocytes (macrophages) and reuptake into the axon terminal. Many neurotransmitters are actively taken back (reuptake) into the nerve terminals with the help of membrane proteins known as neurotransmitter transporters and repacked into new synaptic vesicles for further actions (Muller and Nistico, 1989; Edwards, 2007).
The Epigenetic Role of Vitamin C in Neurological Development and Disease
Published in Qi Chen, Margreet C.M. Vissers, Vitamin C, 2020
Despite the absence of extensive investigation, vitamin C may also play a role in serotonin biosynthesis and the downstream behavior associated with serotonergic signaling. Serotonin is a pervasive neurotransmitter common to many physiologic processes but is most notably associated with mood [59]. The link between serotonin and mood is most salient in mood disorders such as depression. Selective serotonin reuptake inhibitors (SSRIs), which prolong serotonin exposure in the synaptic cleft, remain the most prescribed form of treatment [60]. Vitamin C has also been implicated in mood disorders, as psychological abnormalities have been found to co-occur with vitamin C deficiency [61–63]. Vitamin C administration has been found to improve symptoms of major depressive disorder in both children and adults as well as bolster mood in healthy individuals [64–68]. Additionally, cotreatment of vitamin C and the SSRI fluoxetine has been shown to significantly decrease depressive symptoms in pediatric patients compared to treatment with fluoxetine and placebo [69]. These studies collectively suggest that vitamin C may curb the symptoms of mood disorders such as depression, putatively through regulation of serotonin though the actual mechanism is unknown.
The neurosciences at the Max Planck Institute for Biophysical Chemistry in Göttingen
Published in Journal of the History of the Neurosciences, 2023
Whittaker and his colleagues were able to show that the neurotransmitters were not released from the cytoplasmic pool, but through fusion of the vesicle with the presynaptic membrane. They were also able to demonstrate that vesicles are “created” in the cell body and are then transported to the synapse in Fast Axonal Transport. Following vesicle fusion with the presynaptic membrane when the neurotransmitters are released, there is a reuptake of the vesicle, which is once again loaded with neurotransmitters. Whittaker and his colleagues studied this vesicle cycle with radioactive marker substances (e.g., Dextran) and with antibodies against specific proteoglycanes they had identified in the vesicle membranes. They also identified and localized other elements of the vesicle membrane. Figure 4 shows how far their knowledge had reached in the year 1984 (Whittaker 1984).
What value do norepinephrine/dopamine dual reuptake inhibitors have to the current treatment of adult attention deficit hyperactivity disorder (ADHD) treatment armamentarium?
Published in Expert Opinion on Pharmacotherapy, 2022
Giulio Perugi, Ugo De Rosa, Margherita Barbuti
In youths and adults with ADHD, currently approved pharmacological agents act by increasing catecholaminergic transmission and include stimulant and non-stimulant medications [6]. Psychostimulant agents (i.e. methylphenidate and amphetamines) are the mainstay of ADHD treatment both in pediatric and adult populations, and act as norepinephrine/dopamine dual reuptake inhibitors. On the other hand, most non-stimulant compounds (i.e. atomoxetine, viloxazine) target mostly the noradrenergic system. Nonetheless, atomoxetine also seems to indirectly increase dopaminergic tone in the prefrontal cortex in animal models [7], while viloxazine, which has recently been approved for the treatment of ADHD in children and adolescents, acts as a serotonin and norepinephrine modulating medication [8]. Third-line drugs include alpha 2A-adrenergic receptor agonists (guanfacine, clonidine), bupropion, modafinil, and tricyclic antidepressant (e.g. desipramine, nortriptyline).
Datumetine exposure alters hippocampal neurotransmitters system in C57BL/6 mice
Published in Drug and Chemical Toxicology, 2022
Azeez Olakunle Ishola, Aminu Imam, Moyosore Salihu Ajao
Electron microscopy studies on the synapse revealed that datumetine exposed animals showed a reduction in the number of viable synapses with 1.0 mg/kg Datumetine animals showing the greatest reduction compared to controls. It is on record that overactivation of NMDAR leads to synaptic loss (Talantova et al.2013, Zhou et al.2013, Lewerenz and Maher 2015). This observation may be due to the persistent interaction of datumetine with NMDAR (Ishola et al.2020). The postsynaptic density was thicker in datumetine exposed animals with a great reduction in presynaptic vesicles. Chemical neurotransmission is through the release of synaptic vesicles (Trkanjec and Demarin 2001, Ikeda and Bekkers 2009) which are tightly regulated by re-uptake back to the presynaptic neurons (Piedras-Renteria et al.2004, Dickman et al.2012, Davis and Muller 2015). Datumetine greatly reducing the number of synaptic vesicles showed that either reuptake of the vesicles is altered, or rate of production is not balanced with the rate of release (Wang et al.2016, Li and Kavalali 2017). Another possible explanation may be that NMDAR binding with datumetine increases the affinity of presynaptic NMDAR for glutamate thereby increasing the release of neurotransmitters (Reimer et al.1998, Takamori 2016).