Glutamine and New Pharmacological Targets to Treat Suicidal Ideation
Glutamate is the major excitatory neurotransmitter in the central nervous system, and it is linked with the amino acid glutamine through a metabolic relationship of enzymatic compound interconversion and transportation, also known as the glutamate-glutami
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ontents 1 The Glutamate-Glutamine Cycle 2 Glutamate-Glutamine Cycle and Psychopathology of Suicide 3 Evidence of Glutamate-Glutamine Cycle Changes in Suicidal Behaviours 3.1 Glutamine Synthetase 3.2 Phosphate-Activated Glutaminase 3.3 Glutamate Receptors 3.4 Glutamate Transporters 4 Glutamine-Glutamate as the Target of New Anti-suicide Drugs 4.1 Glutamine Synthetase 4.2 NMDA Receptor 5 Conclusion References
Abstract Glutamate is the major excitatory neurotransmitter in the central nervous system, and it is linked with the amino acid glutamine through a metabolic relationship of enzymatic compound interconversion and transportation, also known as the glutamate-glutamine cycle.
L. Jimenez-Treviño, L. Gonzalez-Blanco, and P. A. Saiz Martinez (*) Department of Psychiatry, University of Oviedo, Oviedo, Spain Biomedical Research Networking Centre in Mental Health (CIBERSAM), Oviedo, Spain Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain Mental Health Services of Principado de Asturias (SESPA), Oviedo, Spain e-mail: [email protected] C. Alvarez-Vázquez Mental Health Services of Principado de Asturias (SESPA), Oviedo, Spain J. Rodríguez-Revuelta Department of Psychiatry, University of Oviedo, Oviedo, Spain Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain Mental Health Services of Principado de Asturias (SESPA), Oviedo, Spain © Springer Nature Switzerland AG 2020 Curr Topics Behav Neurosci https://doi.org/10.1007/7854_2020_168
L. Jimenez-Treviño et al.
A growing body of evidence suggests involvement of the glutamatergic neurotransmitter system in suicidal behaviours. The initial evidence comes from the pathophysiology of neuropsychiatric disorders, as disruptions in glutamate neurotransmission have been found underlying pathology in multiple suicide-related psychiatric conditions such as major depressive disorder, schizophrenia, posttraumatic stress disorder, and bipolar disorder. Existing data from experimental animal models and human in vivo studies also demonstrate that glutamate plays a key role in suicide-related personality traits including aggression and impulsive aggression. Further studies on glutamate system dysfunction underlying suicidal behaviours have focused on the different steps of the glutamate-glutamine cycle: an inflammation-mediated reduction of glutamine synthetase activity has been found in depressed suicide attempters, phosphate-activated glutaminase genes are reduced in suicide completers, and gene expression abnormalities in NMDA receptors have also been discovered in suicide victims. Evidence of a role of the glutamate-glutamine cycle in suicidal behaviours unveils new targets for anti-suicide interventions. Lithium’s mechanism to reduce the risk of suicide in people with mood disorders may be related to its ability to increase glutamine synthetase, whereas novel NMDA antagonists such as ketamine [or its S(+) enantiomer esketamine] have already demonstrated positive results in reducing suicidal ideation. Keywords Esketamine
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