title: Long-term effects of repetitive transcranial magnetic stimulation on markers for neuroplasticity: differential outcomes in anesthetized and awake animals.
abstract: Long-term effects of repetitive transcranial magnetic stimulation (rTMS) have been associated with neuroplasticity, but most physiological studies have evaluated only the immediate effects of the stimulation on neurochemical markers. Furthermore, although it is known that baseline excitability state plays a major role in rTMS outcomes, the role of spontaneous neural activity in metaplasticity has not been investigated. The first aim of this study was to evaluate and compare the long-term effects of high- and low-frequency rTMS on the markers of neuroplasticity such as BDNF and GluR1 subunit of AMPA receptor. The second aim was to assess whether these effects depend on spontaneous neural activity, by comparing the neurochemical alterations induced by rTMS in anesthetized and awake rats. Ten daily sessions of high- or low-frequency rTMS were applied over the rat brain, and 3 d later, levels of BDNF, GluR1, and phosphorylated GluR1 were assessed in the hippocampus, prelimbic cortex, and striatum. We found that high-frequency stimulation induced a profound effect on neuroplasticity markers; increasing them in awake animals while decreasing them in anesthetized animals. In contrast, low-frequency stimulation did not induce significant long-term effects on these markers in either state. This study highlights the importance of spontaneous neural activity during rTMS and demonstrates that high-frequency rTMS can induce long-lasting effects on BDNF and GluR1 which may underlie the clinical benefits of this treatment in neuroplasticity-related disorders.
authors: Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Roman
authors: R
authors: Gersner
authors: Elena
authors: E
authors: Kravetz
authors: Jodie
authors: J
authors: Feil
authors: Gaby
authors: G
authors: Pell
authors: Abraham
authors: A
authors: Zangen
references: Addiction. 2009 Apr;104(4):653-60
references: 19183128
references: Pharmacopsychiatry. 2006 Mar;39(2):52-9
references: 16555165
references: Brain Stimul. 2010 Apr;3(2):95-118
references: 20633438
references: Neuroreport. 2004 Mar 22;15(4):717-20
references: 15094483
references: Cortex. 2009 Oct;45(9):1035-42
references: 19371866
references: Brain Res. 1996 May 25;722(1-2):217-21
references: 8813372
references: Clin Neurophysiol. 2006 Dec;117(12):2584-96
references: 16890483
references: Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15788-92
references: 15505222
references: Prog Neurobiol. 2005 Jun;76(2):99-125
references: 16099088
references: J Neurosci. 2009 Jul 8;29(27):8688-97
references: 19587275
references: Am J Psychiatry. 2002 Jul;159(7):1093-102
references: 12091184
references: Curr Opin Neurobiol. 1994 Jun;4(3):389-99
references: 7919934
references: Psychopharmacology (Berl). 2006 Jul;187(1):56-9
references: 16767416
references: Clin Neurophysiol. 2002 Aug;113(8):1249-57
references: 12140004
references: J Neurophysiol. 1995 Oct;74(4):1793-9
references: 8989415
references: Neuron. 1996 Jun;16(6):1179-88
references: 8663994
references: J Neurochem. 2008 Oct;107(2):522-32
references: 18752645
references: Neuron. 2004 Sep 30;44(1):5-21
references: 15450156
references: J Huazhong Univ Sci Technolog Med Sci. 2007 Aug;27(4):415-8
references: 17828499
references: Exp Brain Res. 2008 Jun;188(2):249-61
references: 18385988
references: Nat Neurosci. 2007 Sep;10(9):1089-93
references: 17726474
references: Prog Neurobiol. 2011 Jan;93(1):59-98
references: 21056619
references: J Affect Disord. 2006 Mar;91(1):83-6
references: 16448701
references: Nature. 2008 Oct 16;455(7215):894-902
references: 18923511
references: Neuropsychopharmacology. 2000 Aug;23(2):205-15
references: 10882847
references: Neuron. 2005 Oct 6;48(1):123-37
references: 16202713
references: J Pharmacol Exp Ther. 2005 Feb;312(2):801-8
references: 15375177
references: Nature. 2000 Jul 13;406(6792):147-50
references: 10910346
references: Eur J Neurosci. 2009 Mar;29(5):964-9
references: 19200060
references: Neuroscience. 2006 Sep 29;142(1):1-20
references: 16887277
references: Neuron. 2005 Jan 20;45(2):201-6
references: 15664172
references: Exp Brain Res. 2007 Jul;180(4):583-93
references: 17562028
references: Clin Neurophysiol. 2009 Dec;120(12):2008-2039
references: 19833552
references: Mol Psychiatry. 2010 Jan;15(1):80-92
references: 19621014
references: Anesthesiology. 2009 Apr;110(4):813-25
references: 19293698
references: J Neurosci. 2007 Apr 4;27(14):3807-12
references: 17409245
references: J Affect Disord. 2008 Apr;107(1-3):255-8
references: 17825920
references: Exp Brain Res. 2008 May;187(2):207-17
references: 18259738
references: Neuron. 2010 Apr 29;66(2):198-204
references: 20434997
references: Clin Neurophysiol. 2010 Apr;121(4):461-3
references: 20064742
references: Curr Drug Targets CNS Neurol Disord. 2003 Apr;2(2):123-9
references: 12769804
references: Biol Psychiatry. 2010 Jan 15;67(2):125-32
references: 19880094
references: BMC Pharmacol. 2008 Mar 04;8:6
references: 18318898
references: Apoptosis. 2006 Sep;11(9):1603-15
references: 16738805
references: J Physiol. 2002 Aug 1;542(Pt 3):951-61
references: 12154192
references: Brain. 1989 Feb;112 ( Pt 1):147-64
references: 2917276
references: Physiol Rev. 2006 Jul;86(3):1033-48
references: 16816145