McAllister BB, Dyck RH. Zinc transporter 3 (ZnT3) and vesicular zinc in central nervous system function. Neurosci Biobehav Rev. 2017;80:329–50.

Article  CAS  PubMed  Google Scholar 

Krall RF, Tzounopoulos T, Aizenman E. The function and regulation of Zinc in the brain. Neuroscience. 2021;457:235–58.

Article  CAS  PubMed  Google Scholar 

Adlard PA, Parncutt J, Lal V, James S, Hare D, Doble P, et al. Metal chaperones prevent zinc-mediated cognitive decline. Neurobiol Dis. 2015;81:196–202.

Article  CAS  PubMed  Google Scholar 

Ayton S, Lei P, Appukuttan AT, Renoir T, Foliaki S, Chen F, et al. Brain Zinc Deficiency exacerbates cognitive decline in the R6/1 model of Huntington’s Disease. Neurotherapeutics. 2020;17(1):243–51.

Article  CAS  PubMed  Google Scholar 

Nakashima AS, Dyck RH. Zinc and cortical plasticity. Brain Res Rev. 2009;59(2):347–73.

Article  CAS  PubMed  Google Scholar 

Kodirov SA, Takizawa S, Joseph J, Kandel ER, Shumyatsky GP, Bolshakov VY. Synaptically released zinc gates long-term potentiation in fear conditioning pathways. Proc Natl Acad Sci U S A. 2006;103(41):15218–23.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Takeda A, Tamano H, Imano S, Oku N. Increases in extracellular zinc in the amygdala in acquisition and recall of fear experience and their roles in response to fear. Neuroscience. 2010;168(3):715–22.

Article  CAS  PubMed  Google Scholar 

Khan MZ, Zheng YB, Yuan K, Han Y, Lu L. Extracellular zinc regulates contextual fear memory formation in male rats through MMP-BDNF-TrkB pathway in dorsal hippocampus and basolateral amygdala. Behav Brain Res. 2023;439(114230):114230.

Article  CAS  PubMed  Google Scholar 

Whittle N, Hauschild M, Lubec G, Holmes A, Singewald N. Rescue of impaired fear extinction and normalization of cortico-amygdala circuit dysfunction in a genetic mouse model by dietary zinc restriction. J Neurosci. 2010;30(41):13586–96.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hershfinkel M. The Zinc sensing receptor, ZnR/GPR39, in Health and Disease. Int J Mol Sci. 2018;19(2).

Besser L, Chorin E, Sekler I, Silverman WF, Atkin S, Russell JT, et al. Synaptically released zinc triggers metabotropic signaling via a zinc-sensing receptor in the hippocampus. J Neurosci. 2009;29(9):2890–901.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang JV, Ren PG, Avsian-Kretchmer O, Luo CW, Rauch R, Klein C, et al. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake. Science. 2005;310(5750):996–9.

Article  CAS  PubMed  Google Scholar 

Lauwers E, Landuyt B, Arckens L, Schoofs L, Luyten W. Obestatin does not activate orphan G protein-coupled receptor GPR39. Biochem Biophys Res Commun. 2006;351(1):21–5.

Article  CAS  PubMed  Google Scholar 

Yasuda S, Miyazaki T, Munechika K, Yamashita M, Ikeda Y, Kamizono A. Isolation of Zn2 + as an endogenous agonist of GPR39 from fetal bovine serum. J Recept Signal Transduct Res. 2007;27(4):235–46.

Article  CAS  PubMed  Google Scholar 

Holst B, Egerod KL, Schild E, Vickers SP, Cheetham S, Gerlach LO, et al. GPR39 signaling is stimulated by zinc ions but not by obestatin. Endocrinology. 2007;148(1):13–20.

Article  CAS  PubMed  Google Scholar 

Ganay T, Asraf H, Aizenman E, Bogdanovic M, Sekler I, Hershfinkel M. Regulation of neuronal pH by the metabotropic zn(2+)-sensing Gq-coupled receptor, mZnR/GPR39. J Neurochem. 2015;135(5):897–907.

Article  CAS  PubMed  Google Scholar 

Jackson VR, Nothacker HP, Civelli O. GPR39 receptor expression in the mouse brain. NeuroReport. 2006;17(8):813–6.

Article  CAS  PubMed  Google Scholar 

Popovics P, Stewart AJ. GPR39: a zn(2+)-activated G protein-coupled receptor that regulates pancreatic, gastrointestinal and neuronal functions. Cell Mol Life Sci. 2011;68(1):85–95.

Article  CAS  PubMed  Google Scholar 

Chorin E, Vinograd O, Fleidervish I, Gilad D, Herrmann S, Sekler I, et al. Upregulation of KCC2 activity by zinc-mediated neurotransmission via the mZnR/GPR39 receptor. J Neurosci. 2011;31(36):12916–26.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Perez-Rosello T, Anderson CT, Schopfer FJ, Zhao Y, Gilad D, Salvatore SR, et al. Synaptic Zn2 + inhibits neurotransmitter release by promoting endocannabinoid synthesis. J Neurosci. 2013;33(22):9259–72.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Blaesse P, Airaksinen MS, Rivera C, Kaila K. Cation-chloride cotransporters and neuronal function. Neuron. 2009;61(6):820–38.

Article  CAS  PubMed  Google Scholar 

Medina I, Friedel P, Rivera C, Kahle KT, Kourdougli N, Uvarov P, et al. Current view on the functional regulation of the neuronal K(+)-Cl(-) cotransporter KCC2. Front Cell Neurosci. 2014;8(27):27.

PubMed  PubMed Central  Google Scholar 

Rivera C, Voipio J, Payne JA, Ruusuvuori E, Lahtinen H, Lamsa K, et al. The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature. 1999;397(6716):251–5.

Article  CAS  PubMed  Google Scholar 

Pressey JC, de Saint-Rome M, Raveendran VA, Woodin MA. Chloride transporters controlling neuronal excitability. Physiol Rev. 2023;103(2):1095–135.

Article  CAS  PubMed  Google Scholar 

Sunuwar L, Gilad D, Hershfinkel M. The zinc sensing receptor, ZnR/GPR39, in health and disease. Front Biosci (Landmark Ed). 2017;22(9):1469–92.

Article  CAS  PubMed  Google Scholar 

Gilad D, Shorer S, Ketzef M, Friedman A, Sekler I, Aizenman E, et al. Homeostatic regulation of KCC2 activity by the zinc receptor mZnR/GPR39 during seizures. Neurobiol Dis. 2015;81:4–13.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen NN, Zhao DJ, Sun YX, Wang DD, Ni H. Long-Term effects of Zinc Deficiency and Zinc Supplementation on Developmental Seizure-Induced Brain damage and the underlying GPR39/ZnT-3 and MBP expression in the Hippocampus. Front Neurosci. 2019;13(920):920.

Article  PubMed  PubMed Central  Google Scholar 

Doboszewska U, Socała K, Pieróg M, Nieoczym D, Sawicki J, Szafarz M, et al. TC-G 1008 facilitates epileptogenesis by acting selectively at the GPR39 receptor but non-selectively activates CREB in the hippocampus of pentylenetetrazole-kindled mice. Cell Mol Life Sci. 2023;80(5):133.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Doboszewska U, Socała K, Pieróg M, Nieoczym D, Sawicki J, Sajnóg A et al. Dietary zinc differentially regulates the effects of the GPR39 receptor agonist, TC-G 1008, in the maximal electroshock seizure test and pentylenetetrazole-kindling model of Epilepsy. Cells. 2023;12(2).

Vinti V, Dell’Isola GB, Tascini G, Mencaroni E, Cara GD, Striano P, et al. Temporal lobe Epilepsy and Psychiatric Comorbidity. Front Neurol. 2021;12(775781):775781.

Article  PubMed  PubMed Central  Google Scholar 

Tellez-Zenteno JF, Patten SB, Jetté N, Williams J, Wiebe S. Psychiatric comorbidity in epilepsy: a population-based analysis. Epilepsia. 2007;48(12):2336–44.

Article  PubMed