Brain Development and Its Relationship to Patterns of Injury
Richard A. Jonas, Jane W. Newburger, Joseph J. Volpe, John W. Kirklin in Brain Injury and Pediatric Cardiac Surgery, 2019
There has been a lot of interest in neurotransmitters over the past few years. For example, dopamine is important in control of movement and the neuropeptides that modulate pain perceptions. However these neurotransmitters pale in significance beside the small amino acids, i.e., glycine, aspartic acid, glutamic acid, and GABA, which carry the majority of messages in the brain. Glutamic acid, as the major excitatory neurotransmitter, conducts most of the excitatory electrical activity in the brain. Most of the input into the reader’s visual cortex from this page is being mediated by the release of glutamate.11 In addition, important glutamatergic pathways include the intracortical association pathways, the cortico-spinal pathways, connections in the hippocampus that are important for learning and memory, and corticostriatal pathways.
Novel psychoactive substances and inhalants
Ilana B. Crome, Richard Williams, Roger Bloor, Xenofon Sgouros in Substance Misuse and Young People, 2019
Several neurotransmitter systems have been hypothesised to be involved in the in vivo effects of inhalants. They are predominantly: the γ-aminobutyric acid (GABA) receptors; the glutamatergic N-methyl-D-aspartic acid (NDMA) receptors; and the dopaminergic mesolimbic system. Abused inhalants, such as toluene, butane, 1,1,1,-trichloroethane, and trichloroethylene, enhance GABA-mediated synaptic inhibition, through pre-synaptic action on the GABA nerve terminals (Hara et al., 2002; MacIver, 2009). This is likely to contribute to the behavioural effects and could be especially important in the context of a disruption of learning and memory by abused inhalants. Butane acts also as a NMDA, and nicotinic acetylcholine receptor antagonist (Hara et al., 2002).
Vitamin C in Neurological Function and Neurodegenerative Disease
Qi Chen, Margreet C.M. Vissers in Vitamin C, 2020
As the dopamine system deteriorates, other neurotransmitter systems within the basal ganglia are also affected. Specifically, altered glutamatergic transmission appears to be a secondary event in the propagation of excitotoxic cell death in PD [233]. The accumulation of α-synuclein is associated with the dysregulation of glutamate receptor-mediated calcium homeostasis in cultured neurons [234]. α-Synuclein is believed to be involved in synaptic transmission through maintenance of the synaptic pool, though the exact relationship is not yet understood [235,236]. Additionally, inhibition of mitochondrial complex 1 in primary astrocyte cultures, alone or in combination with depletion of the antioxidant glutathione, caused an increase in the extracellular concentrations of glutamate and hydrogen peroxide [237], thereby increasing the likelihood of excitotoxic and oxidative damage. However, vitamin C preloading protected dopamine-like neurons derived from SH-SY5Y cells against glutamate-induced excitotoxicity in a dose-dependent manner [75].
Glutamatergic dysregulation in mood disorders: opportunities for the discovery of novel drug targets
Published in Expert Opinion on Therapeutic Targets, 2020
Panek Małgorzata, Kawalec Paweł, Malinowska Lipień Iwona, Tomasz Brzostek, Pilc Andrzej
The glutamatergic system is a major brain-stimulating system, with glutamate (Glu) as the primary neurotransmitter. Glutamatergic projections connect a number of brain structures such as the efferent routes from the cortex to the thalamus as well as to the nucleus accumbens, septum, and amygdala. Glu reaches synaptic vesicles via the vesicular glutamate transporter and is secreted from presynaptic endings in response to neuronal depolarization. This is followed by glutamate reuptake into cells (such as glial, brain and neuronal cells) via the excitatory amino-acid transporter (EAAT). The conversion of Glu to glutamine occurs in glial cells, by a reaction catalyzed by the enzyme glutamine synthetase, which occurs only in these cells. Glutamine is released to the extracellular space, from where it is absorbed back to glutamatergic neurons. Glutamine is again converted into glutamate by the glutaminase enzyme [13].
Glial endocannabinoid system in pain modulation
Published in International Journal of Neuroscience, 2019
Jing Wang
Glutamate is the major excitatory neurotransmitter acting on two classifications of receptors: metabotropic glutamatergic receptors including mGluR group I-III, and ionotoropic glutamatergic receptors including AMPA receptor, KA receptor and NMDA receptor. Except for neurons, these receptors are also found to be expressed on glial cells [71–75]. It is found that SNI results in upregulation of AMPA receptors in microglia of prelimbic and infralimbic cortex. Injection of mGluR5 and NMDA receptor antagonists into the prelimbic and infralimbic cortex augmented the neuropathic pain while injection of AMPA receptor antagonists and a CB1 agonist attenuated the neuropathic pain in SNI mice [65]. Intrathecal injection of CB2 agonist can attenuate the mechanical allodynia and thermal hypderalgesia induced by remifentanil, expression of NR2B-containing NMDAR, cytokine expression of IL-6 and TNFα, but increase the expression of CB2 [76]. In addition, it is found that activation of CB receptor in astrocytes can impair synaptic plasticity [77] which is a molecular basis underlying the mechanism of neuropathic pain. These results suggest that the interaction of glial CB receptor and glutamatergic receptor plays important role in the ECs-mediated pain modulation.
Targeting GSK3 signaling as a potential therapy of neurodegenerative diseases and aging
Published in Expert Opinion on Therapeutic Targets, 2018
Przemysław Duda, Janusz Wiśniewski, Tomasz Wójtowicz, Olga Wójcicka, Michał Jaśkiewicz, Dominika Drulis-Fajdasz, Dariusz Rakus, James A. McCubrey, Agnieszka Gizak
Fundamentally different mechanisms underlie glutamatergic and GABAergic synaptic plasticity. In contrast to glutamate-dependent LTP, GSK3β activation and GSK3β-mediated phosphorylation of gephyrin (Ser270) induces the formation of new GABAergic synapses and hence, it stimulates iLTP [30,66]. On the other hand, elevation of calcium stimulates gephyrin proteolysis by calpain-1 and induces iLTD via limiting of the number of functional GABAR containing inhibitory synapses [30]. Evidently, the postsynaptic role of GSK3 differs depending on cellular mechanisms of memory formation: the active GSK3 is related to formation of LTD and iLTP but it inhibits LTP and iLTD. In other words, active GSK3 downsizes the strength of synaptic connections related to the excitatory transmission but it boosts the inhibitory ones. In the presynaptic part, the active GSK3 is presumed to influence neurotransmitter release by inhibition of exocytosis of neurotransmitter-containing vesicles [62,67], inhibiting thus any kind of synaptic transmission. Globally, it has been reported that administration of GSK3 inhibitors improves spatial memory and ameliorates cognitive deficits in animal models of CNS diseases (reviewed in [68,69]); however, these actions are supposedly attributed to the long-term effect of GSK3 inhibition, not to the immediate/direct regulation of synaptic plasticity by the kinase.
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