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Pain Sensitization
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Pharmacological studies have identified the many neurotransmitters and neuromodulators that are involved in pain processes in the dorsal horn. The excitatory amino acid glutamate has a major role in nociceptive transmission in the dorsal horn. Glutamate acts at NMDA receptors, non-NMDA receptors such as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate and metabotropic glutamate receptors (Figure 71.2).
A Neurochemical Approach to Elucidate Metabotropic vs. Ionotropic Glutamate Receptor Activities in Rat Hippocampal Slices
Published in Avital Schurr, Benjamin M. Rigor, BRAIN SLICES in BASIC and CLINICAL RESEARCH, 2020
Darryle D. Schoepp, Manisha A. Desai
One of the primary ways used to describe the functions of ionotropic glutamate receptors in hippocampus has been to study agonist-induced electrophysiological responses. However, distinct properties of these receptor subtypes have also been described with the use of a biochemical assay in which ionotropic glutamate receptor-induced neurotransmitter release is measured. In the hippocampus, ionotropic glutamate receptors modulate the release of a number of neurotransmitters that are either intrinsic to the hippocampal formation or that are released in the hippocampus from extrinsic afferents.49 For instance, studies measuring excitatory amino acid-induced release of 3-norepinephrine (3H-NE) have provided a great deal of information on the regulation of ionotropic glutamate receptors in the hippocampal formation.
Pharmacological Management of Amyotrophic Lateral Sclerosis
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Shalini Mani, Chahat Kubba, Tanya Sharma, Manisha Singh
Glutamate communicates with an assortment of definite receptor and system for transportation to create a functional synapse during the excitatory action in the CNS. Excitotoxicity is a phenomenon caused due to excessive stimulation of glutamate receptors shown in both acute as well as chronic neurodegenerative diseases. Extreme and deregulated activation of glutamate receptors is the primary cause of excitotoxicity. When these receptors are exposed to high or steadily increasing concentrations of glutamate for lengthened periods of time, the cells expressing these receptors begin to die (Choi, 1994). In physiologic circumstances, glutamate level are retained at nanomolar concentration range (Herman and Jahr, 2007), which is insufficient to cause high-affinity glutamate receptor activation. However, glutamate concentration can rise upto millimolar amounts during synaptic discharge events (Beato and Scimemi, 2009). Ca2+-permeable receptors primarily cultivate excitotoxicity. Incursion of Ca2+ is buffered by the endoplasmic reticulum (ER) and the mitochondria are responsible for the moderation of Ca2+, and disturbance of intracellular compartmentalization of Ca2+ or its surplus can lead to cell death (Bonda et al., 2011).
Oleanolic acid and ursolic acid: therapeutic potential in neurodegenerative diseases, neuropsychiatric diseases and other brain disorders
Published in Nutritional Neuroscience, 2023
Chen Chen, Qidi Ai, Axi Shi, Nan Wang, Lina Wang, Yuhui Wei
Rai et al. found that UA (25 mg/kg) can improve the behavioral defects of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-induced PD mouse model, restore dopamine levels and protect dopaminergic neurons [37]. The research team subsequently discovered that MPTP causes increased expression of IBA1 and TNF-α, and activation of NF-κB, and these increased inflammatory response markers can also be reversed by UA (25 mg/kg), thereby acting as a neuroprotective agent [38]. In a rotenone-induced PD rat model, UA (5, 10 mg/kg) is found to improve motor function and cognitive dysfunction significantly, which may be attributed to the protection of TH (tyrosine hydroxylase)-positive neurons from degeneration. In addition, the oxidative stress and inflammation caused by rotenone are greatly reduced by UA. Mitochondrial dysfunction is also one of the pathogenic mechanism underlying PD, and UA can eliminate the inhibitory effect of rotenone on mitochondrial complex I and promote mitochondrial biogenesis [39]. α-synuclein (α-syn) plays a central role in the pathogenesis of PD, and UA (25 mg/kg) can reduce the overexpression of α-syn and regulate phosphorylation of signaling kinases related to cell survival including Akt and ERK in a rotenone-induced PD mouse model [40]. Excitotoxicity is the rapid neuronal death caused by glutamate receptor activation. When UA is at a low concentration (5-15 μM), it can resist the formation of free radicals and the decrease of mitochondrial membrane potential induced by kainic acid, a glutamate receptor agonist, and thus play a neuroprotective role [41].
Dopaminergic and glutamatergic biomarkers disruption in addiction and regulation by exercise: a mini review
Published in Biomarkers, 2022
Muhammad Abdullah, Li-Chung Huang, Shih-Hsien Lin, Yen Kuang Yang
Similarly, glutamatergic projections from the prefrontal cortex, anterior cingulate cortex, hippocampus and amygdala to the ventral tegmental area (VTA) and NAc play a central role in addiction initiation, drug-associated memory consolidation, abstinence and relapse (Tzschentke and Schmidt 2003, Yager et al.2015). These projections of glutamatergic neurons increase dopamine release from the dopaminergic nerve endings into the NAc. Studies have shown that blockage of these projections either by lesions or inhibition through glutamate receptor antagonists prevent addiction-related behaviours, and cue associated reinstatement and relapse (Yager et al.2015). Pharmacological agents acting as NMDA or AMPA receptor antagonists have been targeted as treatments for drug addiction in animal and clinical studies (D’Souza 2015, Olive 2016). Furthermore, cortical and thalamocortical glutamatergic projections have direct synaptic connections with D1 and D2 medium spiny neuron (MSNs), which have a postulated role in the reward pathway (Gardoni and Bellone 2015).
Clinical effects and outcomes of perampanel overdoses reported to U.S. poison centers
Published in Clinical Toxicology, 2022
Faisal Syed Minhaj, James B. Leonard, Wendy Klein-Schwartz
Perampanel is a newer antiepileptic agent that was approved in the United States in 2012 for use in adults with partial onset seizures [1]. The mechanism of action for perampanel is unique among antiepileptic agents as it inhibits glutamate activity on AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. Glutamate is the primary excitatory neurotransmitter in the central nervous system acting on AMPA glutamate receptors. Perampanel is thought to antagonize this receptor and decrease the overstimulation that can occur with seizure activity, leading to decreased signal transmission. Currently, there are few published case reports describing acute overdose [2–5]. Reported symptoms include prolonged central nervous system depression, respiratory depression, and aggressive behavior requiring chemical and physical restraints. Recently, approval was expanded for more seizure disorders and for use in the pediatric population, potentially increasing availability.