in learning, memory, voluntary movement control, attention, sleep regulation, and consciousness. These actions appear to be mediated through cholinergic neurons in the substance to be characterized and identified as a neurotransmitter in the peripheral nervous system. From the cholinergic presynaptic neurons, ACh is transported to synaptic vesicles through the vesicular ACh transporters. After the depolarization of neurons, it is released into the synaptic cleft, where it enables neuromodulator, impacting numerous motor and cognitive functions through cortical and subcortical transmission in the cortical–striatal–thalamocortical circuits. Abnormalities of ACh function in these circuits have been linked to neurological conditions such as schizophrenia and Parkinson’s disease. ACh abnormalities also appear to be involved in myasthenia gravis, sleep disorders, attention disorders, and behavioral disorders (Wu et al., 2022). Other classes of important noncanonical neurotransmitters include enumerated purines such as adenosine triphosphate (ATP); soluble gases (known as gasotransmitters) such as carbon monoxide (CO), nitric oxide, and hydrogen sulfide (H2S); and various neuropeptides, including somatostatin, β -endorphins (Pilozzi et al., 2020), vasopressin, neurotensin, substance P, and neuropeptide Y. Neuropeptide Y is one of the most widely expressed neurotransmitters in the nervous system. In neurology, animal neurotransmission by binding to ACh receptors. In the central nervous system, ACh also acts as a model research has confirmed this molecule is the most abundant peptide in the mammalian brain. Neuropeptide Y appears to have primary roles in various biological processes, Noncanonical Neurotransmitters As mentioned earlier, the term noncanonical neurotransmitters refers to neuroactive compounds that have been recently classified as neurotransmitters under certain conditions. Moieties that fall under this classification in neurologic science are still under research scrutiny. Of this class of neurotransmitters, exosomes have received a substantial amount of research focus This subtype of small bilipid layer extracellular vesicles seem to function as long-range chemical messengers with roles in the regulation of growth and development that facilitate intercellular communication, the modulation of antigen presentation and inflammation, and the promotion of various stages of tumorigenesis. They also serve as mediators or regulators of neurotransmission and are morphologically similar to synaptic vesicles, yet they are released by their parent cells into extracellular spaces. See Figure 7.
controlling and regulating cortical excitability, stress response, food intake, circadian rhythms, and cardiovascular function. Psychopharmacological studies on neuropeptide Y focus on examining its direct influence on behavior and neuronal transmission. These studies have linked impairments in neuropeptide Y synthesis and release to a range of neurological conditions, including epilepsy. In the class of soluble gas neurotransmitters, NO (nitric oxide) is one of the most studied neurotransmitters. It is a significant signaling molecule and regulator of synaptic plasticity. As with serotonin, this molecule appears to have a modulatory effect on the synthesis and release of other neurotransmitters. For instance, it exerts a modulatory effect on the biosynthesis of D-serine in humans. NO is produced in response to NMDA transmission and may diffuse to cells generating D-serine as a way to inhibit feedback (Wang, Serratrice et al., 2021). Commonly dubbed the energy currency of the biological cell, ATP also exerts some neurotransmitter effect in the nervous system. As a source of readily usable energy, ATP is also required for signaling functions in muscle contraction, active transport, and DNA/RNA synthesis. Because synaptic transmission is an energy-demanding process, ATP is required at the presynaptic terminal to regulate ion gradients that move neurotransmitters into vesicles and to prepare for vesicle release through exocytosis. In the CNS, ATP is recognized as an excitatory neurotransmitter in neuron synapses. Impairments in the production and release of ATP have been linked with many neurological dysfunctions, including brain injuries, strokes, Parkinson’s disease, and Alzheimer’s disease. removal, axon regeneration, neurotransmitter production, and recycling. As a vesicle-like moiety, exosomes house various units of synaptotagmin-4 (Syt4), AMPA receptor (AMPAR), and Wnt, which regulate synaptic plasticity. Of significance in neurology, these units exert various influences on neuronal transmission and by extension, behavior. For instance, Syt4 trans-synaptic delivery augments synaptic growth and presynaptic release properties, and AMPAR further improves neuronal excitability. On the other hand, the Wnt ligand on neuronal exosomes activates Wnt signaling in an action that regulates synaptic assembly, neurotransmitter release, and synapse remodeling. The classification of exosomes as nonconical neurotransmitters in psychopharmacology is based on the many actions they have that are similar to those of the principal neurotransmitters. Exosomes are released from presynaptic neurons as a
In neurological transmissions, exosomes modify presynaptic and postsynaptic signaling; control neurotransmitter release; support synapses; and enhance/suppress neurite growth and response to action potential triggers, and they may transport neuropeptides and other ligands in a process that ultimately activates different postsynaptic receptors and generates inositol 1,4,5-triphosphate (IP3). Figure 7: (A) Schematic representation of the function of neuronal exosomes as neuromodulators. (B) Proposed models for neuronal exosomes as neurotransmitters
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).
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