Participation of Glutamatergic Ionotropic Receptors in Excitotoxicity: The Neuroprotective Role of Prolactin. (1st May 2021)

• Record Type: Journal Article
• Authors: Rodriguez-Chavez, V.; Moran, J.; Molina-Salinas, G.; Zepeda Ruiz, W.A.; Rodriguez, M.C.; Picazo, O.; Cerbon, M.
• Is Part Of: Neuroscience. Volume 461(2021)
• Page Start: 180
• Page End: 193
• Publication Date: 2021-05-01
• Subjects: AD Alzheimer's disease -- AIF Apoptosis-inducing factor -- AKT Protein kinase B -- ALS Amyotrophic Lateral Sclerosis -- AMPAR Alfa-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor -- BDNF Brain-derived neurotrophic factor -- Ca2+ Calcium -- cAMP Cyclic adenosine monophosphate -- CREB cAMP responsive element binding protein -- CTD Carboxyl terminal domain -- DG Dentate gyrus -- DR Delta receptor -- E2 Estradiol -- ECD Extracellular domain -- ER Endoplasmic reticulum -- ERK Extracellular signal-regulated kinase -- FOXO Group of transcription factors -- GD Glucose deprivation -- GH Growth hormone -- Gln Glutamine -- Glu Glutamate -- ICD Intracellular domain -- IGF-1 Insulin-like growth factor 1 -- iGluRs Ionotropic glutamatergic receptors -- IP3Rs Inositol-1, 4, 5-tris-phosphate receptors -- JACOB Synapto-nuclear messenger protein -- K+ Potassium -- KAR Kainic Acid receptor -- LBD Ligand-binding domain -- LTD Long-term depression -- LTP Long-term potentiation -- MAPK Mitogen-activated protein kinase -- Mg2+ Magnesium -- MK-801 Dizocilpine hydrogen malate -- Na+ Sodium -- NCX Na+/Ca2+ exchanger -- NFT Neurofibrillary tangles -- NMDAR N-methyl-d-aspartate acid receptor -- NTD Amino terminal domain -- OVX Ovariectomized rats -- p-AKT Phospho AKT -- PD Parkinson's disease -- PMCA Plasmatic membrane Ca2+ transporters -- PRL Prolactin -- ROS Reactive oxygen species -- RyRs Ryanodine receptors -- SLC High-affinity glutamate and neutral amino acid transporter family -- TPA Tissue-type plasminogen activator -- βA Beta amyloid; glutamatergic receptors -- excitotoxicity -- prolactin -- neuroprotection; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2021.02.027
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Glutamate overstimulation induces excitotoxicity and neuronal cell death. Excitotoxicity is involved in several neurological and neurodegenerative diseases. Advances have been made in the knowledge of neuroprotection against excitotoxicity. Prolactin is promising hormone for neuroprotection against excitotoxicity. Abstract: Glutamate (Glu) is known as the main excitatory neurotransmitter in the central nervous system. It can trigger a series of processes ranging from synaptic plasticity to neurophysiological regulation. To carry out its functions, Glu acts via interaction with its cognate receptors, which are ligand-dependent. Glutamatergic receptors include ionotropic and metabotropic categories. The first allows the passage of ions through the postsynaptic membrane, while the metabotropic subtype activates signaling cascades through second messengers. It is well known that an excess of extracellular Glu concentration induces overstimulation of ionotropic glutamatergic receptors (iGluRs), causing the excitotoxicity phenomenon that leads to neuronal damage and cell death. Excitotoxicity plays a crucial role in different brain pathologies such as brain strokes, epilepsy and neurodegenerative disorders. However, until now, there are no effective neuroprotective compounds to prevent or rescue neurons from excitotoxicity. Thus, the continuous elucidation of the molecular mechanisms underlying excitotoxicity in order to prevent damage or neuronal death is necessary. Therefore, the aim of this review was to summarize the current knowledge regarding iGluRs, while describing their structures and molecular mechanisms of action, including their role in excitotoxicity, as well as the current strategies to reduce excitotoxic damage. Particularly, strategies mediated by prolactin, a somatotropin family-related hormone that displays a significant neuroprotective effect against both Glu and kainic acid-induced excitotoxicity in the hippocampus, are described. Finally, the role of prolactin as a possible molecule in the treatment of excitotoxicity in neurological diseases is discussed.