Canonical Neurotransmitters Based on chemical composition and reactions, three different classes of neurotransmitters are commonly studied: Amines, amino acids, and other molecules. Based on their activities, these classes can be further subdivided into positive neurotransmitters, negative neurotransmitters, central neurotransmitters, and peripheral neurotransmitters. See Figure 5. Figure 5: Classification of Neurotransmitters
released into the extracellular region through different pathways. In its entirety, this control and conversion mechanism maintains glutamate homeostasis at the glutamatergic synapse (Satarker et al., 2022). Figure 6. Glutamate Homeostasis at the Tripartite Glutaminergic Synapse
Note . From “Neurotransmitters – Key factors in neurological and neurodegenerative disorders of the cranial nervous system,” by Teleanu, et al., 2022. International Journal of Molecular Science, 23(11):5594. (https://pubmed.ncbi.nlm.nih.gov/35682631/). Courtesy of the National Library of Medicine (NLM). The glutamatergic synapse seems to be an important contributor to cognitive functioning, including learning and memory functions. Research has also described its principal role in long- term potentiation. Motor, sensory, and autonomic activities are other biological functions that rely heavily on the actions of the glutamatergic synapse (Iovino et al., 2020). Primarily, the results of the different regulatory actions at this synapse directly affect the levels of glutamate in the extracellular environment, which influences the physiological range of adequate neuronal transmission. An alteration or malfunction of this control can lead to an imbalance in extracellular levels of glutamate and trigger the onset of neurological pathologies, including epilepsy (Alcoreza et al., 2021), Alzheimer’s disease (Dejakaisaya et al., 2021), Huntington’s disease, and amyotrophic lateral sclerosis (Kazama et al., 2020). GABA ( γ -aminobutyric acid) is another amino acid neurotransmitter that is important in neurological studies of human behavior. Doubling as the main inhibitory neurotransmitter in the brain, GABA is formed through three different pathways: Glutamate decarboxylation (Perry et al., 2022), the conversion of glutamate to GABA, and production by commensal organisms from the gut microbiota. In sharp contrast to glutamate, the neurobehavioral functions of GABA appear to be more complicated and dependent on many secondary influences. For instance, animal model studies have confirmed that GABA functions initially as an excitatory neurotransmitter inducing depolarization instead of hyperpolarization in the central nervous system. These actions are generally described in the neocortex, hippocampus, hypothalamus, spinal cord, and cerebellum. On further investigation, the excitatory action of GABA results from the existence of a higher chloride concertation in the neurons at the early developmental stages of the CNS, which results in an outward instead of an inward chloride flux.
Note . From “Neurotransmitters – Key factors in neurological and neurodegenerative disorders of the cranial nervous system,” by Teleanu, et al., 2022. International Journal of Molecular Science, 23(11):5594. (https://pubmed.ncbi.nlm.nih.gov/35682631/). Courtesy of the National Library of Medicine (NLM). Amino Acids In psychopharmacology, amino acids (canonical neurotransmitters) act as important chemical messengers with significant roles in the CNS. Early research on the role of amino acids in behavioral science suggested that glutamate; glycine; and the γ-amino acids, including γ-aminobutyric acid (GABA) are implicated in the pathology of different metal disorders affecting brain chemistry. In the central nervous system, glutamate in particular acts as the predominant excitatory neurotransmitter. It is the precursor of GABA and is produced from glutamine. In neuronal transmission, glutamate is released from presynaptic neurons into the synaptic cleft, triggering the activation of N-methyl-D-aspartate (NMDA) and alpha-amino-2- hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors in an action that mediates the influx of calcium and sodium into the postsynaptic neuron. As a result, AMPA activation ultimately leads to extreme neuronal firing and excitotoxicity, a mechanism implicated in the pathology of several neurological conditions, including Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis (Le Gall et al., 2020). Controlling extracellular levels of glutamate is important and appears to be the limiting factor between the onset of neurological conditions and normal brain functioning. See Figure 6. This regulation is controlled by the release and uptake mechanisms of astrocytes. Astrocytes generally mediate glutamate uptake and its conversion to glutamine and transport it to the presynaptic neurons. Only a percentage of the glutamate is converted to glutamine, with a certain amount also
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