Recent studies have highlighted the important role of the postsynaptic NMDAR-PSD95-CaMKII pathway for synaptic transmission and related neuronal injury. Here, we tested changes in the components of this pathway upon microwave-induced neuronal structure and function impairments. Ultrastructural and functional changes were induced in hippocampal neurons of rats and in PC12 cells exposed to microwave radiation. We detected abnormal protein and mRNA expression, as well as posttranslational modifications in the NMDAR-PSD95-CaMKII pathway and its associated components, such as synapsin I, following microwave radiation exposure of rats and PC12 cells. Thus, microwave radiation may induce neuronal injury via changes in the molecular organization of postsynaptic density and modulation of the biochemical cascade that potentiates synaptic transmission.

1.
Kesari KK, Kumar S, Behari J: Pathophysiology of microwave radiation: effect on rat brain. Appl Biochem Biotechnol 2012;166:379-388.
2.
Mortazavi SM, Mahbudi A, Atefi M, Bagheri S, Bahaedini N, Besharati A: An old issue and a new look: electromagnetic hypersensitivity caused by radiations emitted by GSM mobile phones. Technol Health Care 2011;19:435-443.
3.
Del Vecchio G, Giuliani A, Fernandez M, Mesirca P, Bersani F, Pinto R, Ardoino L, Lovisolo GA, Giardino L, Calza L: Effect of radiofrequency electromagnetic field exposure on in vitro models of neurodegenerative disease. Bioelectromagnetics 2009;30:564-572.
4.
Rebola N, Srikumar BN, Mulle C: Activity-dependent synaptic plasticity of NMDA receptors. J Physiol 2010;588:93-99.
5.
Cavara NA, Hollmann M: Shuffling the deck anew: how NR3 tweaks NMDA receptor function. Mol Neurobiol 2008;38:16-26.
6.
Schrattenholz A, Soskic V: NMDA receptors are not alone: dynamic regulation of NMDA receptor structure and function by neuregulins and transient cholesterol-rich membrane domains leads to disease-specific nuances of glutamate-signalling. Curr Top Med Chem 2006;6:663-686.
7.
Lau CG, Zukin RS: NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders. Nat Rev Neurosci 2007;8:413-426.
8.
Swulius MT, Kubota Y, Forest A, Waxham MN: Structure and composition of the postsynaptic density during development. J Comp Neurol 2010;518:4243-4260.
9.
Moyano S, Frechilla D, Del Rio J: NMDA receptor subunit and CaMKII changes in rat hippocampus induced by acute MDMA treatment: a mechanism for learning impairment. Psychopharmacology (Berl) 2004;173:337-345.
10.
Sanhueza M, Fernandez-Villalobos G, Stein IS, Kasumova G, Zhang P, Bayer KU, Otmakhov N, Hell JW, Lisman J: Role of the CaMKII/NMDA receptor complex in the maintenance of synaptic strength. J Neurosci 2011;31:9170-9178.
11.
Xu M, Chandler LJ, Woodward JJ: Ethanol inhibition of recombinant NMDA receptors is not altered by coexpression of CaMKII-alpha or CaMKII-beta. Alcohol 2008;42:425-432.
12.
Gardoni F, Mauceri D, Malinverno M, Polli F, Costa C, Tozzi A, Siliquini S, Picconi B, Cattabeni F, Calabresi P, Di Luca M: Decreased NR2B subunit synaptic levels cause impaired long-term potentiation but not long-term depression. J Neurosci 2009;29:669-677.
13.
Gardoni F, Polli F, Cattabeni F, Di Luca M: Calcium-calmodulin-dependent protein kinase II phosphorylation modulates PSD-95 binding to NMDA receptors. Eur J Neurosci 2006;24:2694-2704.
14.
Bayer KU, De Koninck P, Leonard AS, Hell JW, Schulman H: Interaction with the NMDA receptor locks CaMKII in an active conformation. Nature 2001;411:801-805.
15.
Wang H, Peng R, Zhou H, Wang S, Gao Y, Wang L, Yong Z, Zuo H, Zhao L, Dong J, Xu X, Su Z: Impairment of long-term potentiation induction is essential for the disruption of spatial memory after microwave exposure. Int J Radiat Biol 2013;89:1100-1107.
16.
Inaloz SS, Dasdag S, Ceviz A, Bilici A: Acceptable radiation leakage of microwave ovens on pregnant and newborn rat brains. Clin Exp Obstet Gynecol 1997;24:215-219.
17.
Suvorov NB, Medvedeva MV, Vasilevskii NN, Ur'iash VV, Aleksandrova ZhG: Cumulated biological effects of microwaves and their reflection in behavior, work capacity, growth of body mass and state of brain neurons (in Russian). Radiobiologiia 1989;29:660-666.
18.
Fukui Y, Hoshino K, Inouye M, Kameyama Y: Effects of hyperthermia induced by microwave irradiation on brain development in mice. J Radiat Res 1992;33:1-10.
19.
Gaidamkin NA, Davydov BI, Zuev VG, Tikhonchuk VS: Ultrastructure of the cerebral cortex in the rat after the effect of electromagnetic impulse (in Russian). Arkh Anat Gistol Embriol 1988;95:14-18.
20.
Zhao L, Peng RY, Wang SM, Wang LF, Gao YB, Dong J, Li X, Su ZT: Relationship between cognition function and hippocampus structure after long-term microwave exposure. Biomed Environ Sci 2012;25:182-188.
21.
Wang L, Peng R, Hu X, Gao Y, Wang S, Zhao L, Dong J, Su Z, Xu X, Gao R, Lei C: Abnormality of synaptic vesicular associated proteins in cerebral cortex and hippocampus after microwave exposure. Synapse 2009;63:1010-1016.
22.
Paoletti P, Neyton J: NMDA receptor subunits: function and pharmacology. Curr Opin Pharmacol 2007;7:39-47.
23.
Elfverson M, Linde AM, Le Greves P, Zhou Q, Nyberg F, Johansson T: Neurosteroids allosterically modulate the ion pore of the NMDA receptor consisting of NR1/NR2B but not NR1/NR2A. Biochem Biophys Res Commun 2008;372:305-308.
24.
Xu SJ, Chen Z, Zhu LJ, Shen HQ, Luo JH: Visual recognition memory is related to basic expression level of NMDA receptor NR1/NR2B subtype in hippocampus and striatum of rats. Acta Pharmacol Sin 2005;26:177-180.
25.
Rammes G, Hasenjager A, Sroka-Saidi K, Deussing JM, Parsons CG: Therapeutic significance of NR2B-containing NMDA receptors and mGluR5 metabotropic glutamate receptors in mediating the synaptotoxic effects of beta-amyloid oligomers on long-term potentiation (LTP) in murine hippocampal slices. Neuropharmacology 2011;60:982-990.
26.
Varas MM, Perez MF, Ramirez OA, de Barioglio SR: Increased susceptibility to LTP generation and changes in NMDA-NR1 and -NR2B subunits mRNA expression in rat hippocampus after MCH administration. Peptides 2003;24:1403-1411.
27.
Cousins SL, Kenny AV, Stephenson FA: Delineation of additional PSD-95 binding domains within NMDA receptor NR2 subunits reveals differences between NR2A/PSD-95 and NR2B/PSD-95 association. Neuroscience 2009;158:89-95.
28.
D'Mello R, Marchand F, Pezet S, McMahon SB, Dickenson AH: Perturbing PSD-95 interactions with NR2B-subtype receptors attenuates spinal nociceptive plasticity and neuropathic pain. Mol Ther 2011;19:1780-1792.
29.
Sun QJ, Duan RS, Wang AH, Shang W, Zhang T, Zhang XQ, Chi ZF: Alterations of NR2B and PSD-95 expression in hippocampus of kainic acid-exposed rats with behavioural deficits. Behav Brain Res 2009;201:292-299.
30.
Xia Z, Dudek H, Miranti CK, Greenberg ME: Calcium influx via the NMDA receptor induces immediate early gene transcription by a MAP kinase/ERK-dependent mechanism. J Neurosci 1996;16:5425-5436.
31.
Kass-Simon G, Zompa MA, Scappaticci AA, Zackroff RV, Hufnagel LA: Nucleolar binding of an anti-NMDA receptor antibody in hydra: a non-canonical role for an NMDA receptor protein? J Exp Zool A Ecol Genet Physiol 2009;311:763-775.
32.
Park CS, Elgersma Y, Grant SG, Morrison JH: α-Isoform of calcium-calmodulin-dependent protein kinase II and postsynaptic density protein 95 differentially regulate synaptic expression of NR2A- and NR2B-containing N-methyl-D-aspartate receptors in hippocampus. Neuroscience 2008;151:43-55.
33.
Xu S, Ning W, Xu Z, Zhou S, Chiang H, Luo J: Chronic exposure to GSM 1800-MHz microwaves reduces excitatory synaptic activity in cultured hippocampal neurons. Neurosci Lett 2006;398:253-257.
34.
Liboff AR, Cherng S, Jenrow KA, Bull A: Calmodulin-dependent cyclic nucleotide phosphodiesterase activity is altered by 20 microT magnetostatic fields. Bioelectromagnetics 2003;24:32-38.
35.
Chao HW, Tsai LY, Lu YL, Lin PY, Huang WH, Chou HJ, Lu WH, Lin HC, Lee PT, Huang YS: Deletion of CPEB3 enhances hippocampus-dependent memory via increasing expressions of PSD95 and NMDA receptors. J Neurosci 2013;33:17008-17022.
36.
Chen XB, Nelson CD, Li X, Winters CA, Azzam R, Sousa AA, Leapman RD, Gainer H, Sheng M, Reese TS: PSD-95 is required to sustain the molecular organization of the postsynaptic density. J Neurosci 2011;31:6329-6338.
37.
Cheng DM, Hoogenraad CC, Rush J, Ramm E, Schlager MA, Duong DM, Xu P, Wijayawardana SR, Hanfelt J, Nakagawa T: Relative and absolute quantification of postsynaptic density proteome isolated from rat forebrain and cerebellum. Mol Cell Proteomics 2006;5:1158-1170.
38.
Chen XB, Vinade L, Leapman RD, Petersen JD, Nakagawa T, Phillips TM, Sheng M, Reese TS: Mass of the postsynaptic density and enumeration of three key molecules. Proc Natl Acad Sci U S A 2005;102:11551-11556.
39.
Wang LF, Peng RY, Hu XJ, Gao YB, Wang SM, Li Y, Wang X, Zhao L, Gao RL, Ma JJ: Influence of microwave radiation on synaptic structure and function of hippocampus in Wistar rats (in Chinese). Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2007;25:211-214.
40.
Vaynman S, Ying Z, Gomez-Pinilla F: Interplay between brain-derived neurotrophic factor and signal transduction modulators in the regulation of the effects of exercise on synaptic-plasticity. Neuroscience 2003;122:647-657.
41.
Wang LF, Peng RY, Hu XJ, Gao YB, Wang SM, Gao RL, Xu XP, Su ZT, Dong J: Influence of microwave radiation on synapsin I expression in PC12 cells and its mechanism (in Chinese). Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2008;24:655-659.
42.
Bykhovskaia M: Synapsin regulation of vesicle organization and functional pools. Semin Cell Dev Biol 2011;22:387-392.
43.
Haddad JJ: N-methyl-D-aspartate (NMDA) and the regulation of mitogen-activated protein kinase (MAPK) signaling pathways: a revolving neurochemical axis for therapeutic intervention? Prog Neurobiol 2005;77:252-282.
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