Citation

Gruenbaum BF, Zlotnik A, Frenkel A, Fleidervish I, Boyko M. Metabolites (Basel) 2022; 12(5).

Copyright

(Copyright © 2022, MDPI: Multidisciplinary Digital Publications Institute)

DOI

10.3390/metabo12050459

PMID

unavailable

Abstract

Depression is a significant cause of disability and affects millions worldwide; however, antidepressant therapies often fail or are inadequate. Current medications for treating major depressive disorder can take weeks or months to reach efficacy, have troubling side effects, and are limited in their long-term capabilities. Recent studies have identified a new set of glutamate-based approaches, such as blood glutamate scavengers, which have the potential to provide alternatives to traditional antidepressants. In this review, we hypothesize as to the involvement of the glutamate system in the development of depression. We identify the mechanisms underlying glutamate dysregulation, offering new perspectives on the therapeutic modalities of depression with a focus on its relationship to blood-brain barrier (BBB) permeability. Ultimately, we conclude that in diseases with impaired BBB permeability, such as depression following stroke or traumatic brain injury, or in neurogenerative diseases, the glutamate system should be considered as a pathway to treatment. We propose that drugs such as blood glutamate scavengers should be further studied for treatment of these conditions. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Language: en

Keywords

human; cognition; suicide; systematic review; traumatic brain injury; ketamine; depression; central nervous system; schizophrenia; mortality; major depression; hippocampus; epilepsy; antidepressant agent; Alzheimer disease; cerebrovascular accident; messenger RNA; hypertension; amyotrophic lateral sclerosis; alanine aminotransferase; aspartate aminotransferase; brain hemorrhage; brain function; positron emission tomography; nuclear magnetic resonance spectroscopy; Parkinson disease; 4 aminobutyric acid; GABAergic system; multiple sclerosis; monoamine; thrombosis; subarachnoid hemorrhage; Article; Huntington chorea; frontal cortex; n methyl dextro aspartic acid; alanine; autoradiography; cerebrospinal fluid; receptor binding; astrocyte; nerve cell plasticity; blood brain barrier; Western blotting; glutamic acid; proton nuclear magnetic resonance; n methyl dextro aspartic acid receptor blocking agent; in situ hybridization; neocortex; serine; excitotoxicity; carotid artery; entorhinal cortex; glutamine; GABAergic transmission; alpha amino 3 hydroxy 5 methyl 4 isoxazolepropionic acid; aquaporin 4; pyruvic acid; pyridoxal 5 phosphate; glutamate receptor; ischemic stroke; glutamatergic transmission; metabotropic receptor; acute ischemic stroke; amino acid receptor affecting agent; aspartate aminotransferase isoenzyme 1; blood glutamate scavengers; blood vessel occlusion; blood–brain barrier; claudin 5; excitatory amino acid; glutamate; glutamate transporter; microdialysis; oxaloacetic acid; oxoglutarate dehydrogenase; perirhinal cortex