Sense and antisense Oligodeoxynucleotides to Glun1 Nmdar are Cognitive Enhancers (Nootropics) and protective agents in normal and ischemic (Anoxic) conditions-In vitro study

Main Article Content

Anatoly A Mokrushin

Abstract

Aims: Implication of modified N-methyl-D-aspartate receptors (NMDAR) in synaptic plasticity and learning was investigated in normal and pathological conditions.


Study design: We studied the efficiency of synaptic plasticity, the development of the long-term potentiation/depression (LTP/LTD) in olfactory cortex slices, treated with antisense or sense oligodeoxynucleotides (aODNs and sODNs) to the GluN1 subunit of NMDAR.


Main outcome: aODNs induced the LTD development in slices after high-frequency tetanization. Contrariwise, in sliced treated with sODNs the enhanced LTP developed. Under conditions of severe anoxia (10 min), treatment of slices with aODNs and sODNs contributed to the preservation of synaptic activity which has been blocked in the control untreated slices. In practical implications such directed up- and down regulation of NMDAR might be useful in the readjustment of brain activity by the controlling balance of excitation/inhibition.

Article Details

Mokrushin, A. A. (2017). Sense and antisense Oligodeoxynucleotides to Glun1 Nmdar are Cognitive Enhancers (Nootropics) and protective agents in normal and ischemic (Anoxic) conditions-In vitro study. Archives of Pharmacy and Pharmaceutical Sciences, 1(1), 013–023. https://doi.org/10.29328/journal.hps.1001003
Research Articles

Copyright (c) 2017 Mokrushin AA.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Traynelis SF, Lonnie PW, Chris JMcB, Frank SM, Katie MV, et al. Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev. 2010; 62: 405-496. Ref.: https://goo.gl/V74An8

Rebola N, Srikumar BN, Mulle C. Activity-dependent synaptic plasticity of NMDA receptors. J Physiol. 2010; 588: 93-99. Ref.: https://goo.gl/7FgVTV

Paoletti P, Neyton J. NMDA receptor subunits: function and pharmacology. Curr Opin Pharmacol. 2007; 7: 39-47. Ref.: https://goo.gl/kEujvi

Cull-Candy SG, Leszkiewicz DN. Role of distinct NMDA receptor subtypes at central synapses. SciSTKE. 2004; 255: 16. Ref.: https://goo.gl/ZhDLx7

Ulbrich MH, Isacoff EY. Rules of engagement for NMDA receptor subunits. PNAS. 2008; 105: 14163-14168. Ref.: https://goo.gl/xw2ZR8

Salussolia CL, Prodromou M, Borker P, Wollmuth LP. Arrangement of subunits in functional NMDA receptors. J Neurosci. 2010; 31: 11295-11304. Ref.: https://goo.gl/KXPdRd

Cammarota M, De Stein ML, Paratcha G, Bevilaqua LR, Izquierdo I, et al. Rapid and transient learning-associated increase in NMDA NR1 subunitin the rat hippocampus. Neurochem Res. 2000; 25: 567-572. Ref.: https://goo.gl/TzCSPK

Bellone C, Nicoll RA. Rapid bidirectional switching of synaptic NMDA receptors. Neuron. 2007; 55: 779-785. Ref.: https://goo.gl/pkNATy

Mahajan SS, Thai KH, Chen K, Ziff E. Exposure of neurons to excitotoxic levels of glutamate induces cleavage of the RNA editing enzyme, adenosine deaminase acting on RNA 2, and loss of GLUR2 editing. Neuroscience. 2011; 25: 305-315. Ref.: https://goo.gl/svz56N

Wright A, Vissel B. The essential role of AMPA receptor GluR2 subunit RNA editing in the normal and diseased brain. Front Mol Neurosci. 2012; 5: 34-37. Ref.: https://goo.gl/NYri12

Weeber EJ, Sweatt JD. Molecular neurobiology of human cognition. Neuron. 2002; 33: 845-848. Ref.: https://goo.gl/yDcD1g

Collingridge GL,Volianskis A, Bannister N, France G, et al. The NMDA receptor as a target for cognitive enhancement. Neuropharmacology. 2013; 64: 13-26. Ref.: https://goo.gl/EfERFG

Lai SK, Wong CKC, Yang MS, Yung KK. Changes in expression of N-methyl-D-aspartate receptor subunits in the rat neostriatum after a single dose of antisense oligonucleotide specific for N-methyl-D-aspartate receptor onesubunit. Neuroscience. 2000; 98: 493-500. Ref.: https://goo.gl/SrvMmE

Lui PW, Yeung CW, Yung WH, Shi Y, Chen LW, et al. Ablation of Gene Expression of N-Methyl-D-Aspartate Receptor One by Antisense Oligonucleotides in Striatal Neurons in Culture. Neurosignals. 2005; 14: 303-316. Ref.: https://goo.gl/SNDjAT

Standaert DG, Testa CM, Rudolf GD, Hollingsworth ZR. Inhibition of N-methyl-D-aspartate glutamate receptor subunit expression by antisense oligonucleotides reveals their role in striatal motor regulation. J Pharmacol Exp Ther. 1996; 276: 342-352. Ref.: https://goo.gl/vSdGQW

Lai SK, Ng TKY, Lau WK, Yang MS, Wong CKC, et al. Selective knock-down of gene expression of N-methyl-D-aspartate receptor one ameliorates parkinsonian motor symptom in 6-hydroxydopamine-lesioned rats. Neurochem Int. 2004; 45: 11-22. Ref.: https://goo.gl/RerZ5L

Rydh-Rinder M, Berge OG, Hokfelt T. Antinociceptive effects after intrathecal administration of phosphodiester-, 2'-allyl-, and C-5-propyne-modified antisense oligodeoxynucleotides targeting the NMDAR1 subunit in mouse. Mol Brain Res. 2001; 86: 23-33. Ref.: https://goo.gl/pCiGkk

Shimoyama N, Shimoyama M, Davis AM, Monaghan DT, Inturrisi CE. An antisense oligonucleotide to the N-methyl-D-aspartate (NMDA) subunit NMDAR1 attenuates NMDA- induced nociception, hyperalgesia, and morphine tolerance. J Pharmacol Exp Ther. 2005; 312: 834-840. Ref.: https://goo.gl/h4YJ8h

Xu A, Duan S, Zeng Y. Effects of intrathecal NMDA and AMPA receptor agonists or antagonists on antinociception of propofol. Acta Pharmacol Sinica. 2004; 25: 1-14. Ref.: https://goo.gl/mqV8i4

Lui PW, Yung KKL. Antisense knockdown of gene expression of NMDA receptor subunits in striatal neurons in culture. Soc Neurosci Abstr. 2001; 27: 2961-2965.

Cui Z, Wang H, Tan Y. Inducible and reversible NR1 knock-out reveals crucial role of the NMDA receptor in preserving remote memories in the brain. Neuron. 2004; 41: 781-793. Ref.: https://goo.gl/WAvru1

Belforte JE, Zsiros V, Sklar E, Jiang Z, Yu G, et al. Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes. Nat Neurosci. 2010; 13: 76-83. Ref.: https://goo.gl/k1XpFC

Rompala GR, Zsiros V, Zhang S, Kolata SM, Nakazawa K. Contribution of NMDA receptor hypofunction in prefrontal and cortical excitatory neurons to schizophrenia-like phenotypes. PLoS One. 2013; 8: 61278. Ref.: https://goo.gl/TXQgT6

Moy SS, Nikolova VD, Riddick NV, Baker LK, Koller BH. Preweaning sensorimotor deficits and adolescent hypersociability in Grin1 knockdown mice. Dev Neurosci. 2012; 34: 159-173. Ref.: https://goo.gl/sKRLy3

Milenkovic M, Mielnik CA, Ramsey AJ. NMDA receptor deficient mice display sexual dimorphism in the onset and severity of behavioural abnormalities. Genes Brain Behav. 2014; 13: 850-862. Ref.: https://goo.gl/qxo2Zh

Grosshans DR, Clayton DA, Coultrap SJ, Browning MD. LTP leads to rapid surface expression of NMDA but not AMPA receptors in adult rat CA1. Nat Neurosci. 2002; 5: 27-33. Ref.: https://goo.gl/N9LUfH

Baez MV, Oberholzer MV, Cercato MC, Snitcofsky M, Aguirre AI, et al. NMDA receptor subunits in the adult rat hippocampus undergo similar changes after 5 minutes in an open field and after LTP induction. PLoS One. 2013; 8: 55244. Ref.: https://goo.gl/5zyu3W

Henderson AK, Pittman QJ, Teskey GC. High frequency stimulation alters motor maps, impairs skilled reaching performance and is accompanied by an upregulation of specific GABA, glutamate and NMDA receptor subunits. Neuroscience. 2012; 215: 98-113. Ref.: https://goo.gl/idmGp7

Mokrushin AA. Peptide-dependent mechanisms of neural plasticity in olfactory cortex slices. Dissertation Doctor Sciences. Pavlov Institute Physiology Russian Academy of Sciences, Saint-Petersburg. Russia. 1997.

Wahlestedt C, Golanov E, Yamamoto S, Yee F, Ericson H, et al. Antisense oligodeoxynucleotides to NMDA-R1 receptor channel protect cortical neurons from excitotoxicity and reduce focal ischaemic infarctions. Nature. 1993; 363: 260-263. Ref.: https://goo.gl/nbgJdW

Mokrushin A, Pavlinova L. Hsp70 promotes synaptic transmission in the brain slices damaged by the contact with blood clot. Eur J Pharmacol. 2012; 677: 55-62. Ref.: https://goo.gl/1AV9Rx

Liu L,Wong TP, Pozza M, Lingenhoehl K, Wang Y, et al. Role of NMDA receptor subtypes in governing the direction of hippocampal synaptic plasticity. Science. 2004; 304: 1021-1024. Ref.: https://goo.gl/AtYDMR

Bloodgood BL, Sabatini BL. Regulation of synaptic signaling by postsynaptic, non-glutamate receptor ion channels. J Physiol. 2008; 586: 1475-1480. Ref.: https://goo.gl/CjH5A7

Citri A, Malenka RC. Synaptic plasticity: multiple forms, functions, and mechanisms. Neuropsychopharmacology. 2008; 33: 18-41. Ref.: https://goo.gl/TWhNSM

Lei S, McBain CJ. Distinct NMDA receptors provide differential modes of transmission at mossy fiber-interneuron synapses. Neuron. 2002; 33: 921-933. Ref.: https://goo.gl/jjWree

Kohr G. NMDA receptor function: subunit composition versus spatial distribution. Cell Tissue Res. 2006; 326: 439-446. Ref.: https://goo.gl/Lwc4Kr

Mayer ML. Structure and mechanism of glutamate receptor ion channel assembly, activition and modulation. Curr Opin Neurobiol. 2011; 21: 283-290. Ref.: https://goo.gl/aLqeHi

Zhong WX, Dong ZF, Tian M, Cao J, Xu L, et al. N-methyl-D-aspartate receptor-dependent long-term potentiation in CA1 region affects synaptic expression of glutamate receptor subunits and associated proteins in the whole hippocampus. Neuroscience. 2006; 141: 1399-1413. Ref.: https://goo.gl/orceEF

Alvarez VA, Ridenour DA, Sabatini BL. Distinct structural and ionotropic roles of NMDA receptors in controlling spine and synapse stability. J Neurosci. 2007; 27: 7365-7376. Ref.: https://goo.gl/N2ciGc

Simòes PF, Silva AP, Pereira F, Marques E, Grade S, et al. Methamphetamine induces alterations on hippocampal NMDA and AMPA receptor subunit levels and impairs spatial working memory. Neuroscience. 2007; 150: 433-441. Ref.: https://goo.gl/wRdQs2

Triller A, Choquet D. Surface trafficking of receptors between synaptic and extrasynaptic membranes: and yet they do move! Trends Neurosci. 2005; 28: 133-139. Ref.: https://goo.gl/PFXYza

Kopp C, Longordo F, Lüthi A. Experience-dependent changes in NMDA receptor composition at mature central synapses. Neuropharmacology. 2007; 53: 1-9. Ref.: https://goo.gl/dnYUxV

Bard L, Groc L. Glutamate receptor dynamics and protein interaction: lessons from the NMDA receptor. Mol Cell Neurosci. 2011; 48: 298-307. Ref.: https://goo.gl/fELEzw

Ladépêche L, Dupuis JP, Groc L. Surface trafficking of NMDA receptors: Gathering from a partner to another. Semin. Cell Dev Biol. 2014; 27: 3-13. Ref.: https://goo.gl/rBmbGS

Roberts EB, Meredith MA, Ramoa AS. Suppression of NMDA receptor function using antisens DNA block ocular dominance plasticity while preserving visual responses. J Neurophysiol. 1998; 80: 1021-1032. Ref.: https://goo.gl/vqJkgh

Gilmour G, Dix S, Fellini L, Gastambide F, Plath N, et al. NMDA receptors, cognition and schizophrenia-testing the validity of the NMDA receptor hypofunction hypothesis. Neuropharmacology. 2012, 62: 1401-1412. Ref.: https://goo.gl/RUCFmc

Machaalani R, Waters KA. Distribution and quantification of NMDA R1 mRNA and protein in the piglet brainstem and effects of intermittent hypercapnic hypoxia (IHH). Brain Res. 2002; 951: 293-300. Ref.: https://goo.gl/rypiZX

Cui H, Hayashi A, Sun HS, Belmares MP, Cobey C, et al. PDZ protein interactions underlying NMDA receptor-mediated excitotoxicity and neuroprotection by PSD-95 inhibitors. J Neurosci. 2007; 27: 9901-9915. Ref.: https://goo.gl/55XrmW

Toro CT, Hallak JE, Dunham JS, Leite JP, Sakamoto AC, et al. The NR1 N-methyl-D-aspartate subunit and brainderived neurotrophic factor in temporal lobe epilepsy hippocampus: a comparison of patients with and without coexisting psychiatric symptoms. Epilepsia. 2007; 48: 2352-2356. Ref.: https://goo.gl/Lp6KHW

MacGregor DG, Avshalumov MV, Rice ME. Brain edema induced by in vitro ischemia: causal factors and neuroprotection. J Neurochem. 2003; 85: 1402-1411. Ref.: https://goo.gl/EqtDir

Samoĭlov MO, Mokrushin AA. Peptide modulation of synaptic plasticity induced by anoxia. Dokl Akad Nauk. 1997; 357: 565-567. Ref.: https://goo.gl/LFZB9

Samoĭlov MO, Mokrushin AA. The role of endogenous neuromodulator peptides in enhancement of the functional tolerance of brain neurons to anoxia. Biull Eksp Biol Med. 1998; 125: 503-505. Ref.: https://goo.gl/fqzj5b