Name: a pilot study on the repetitive transcranial magnetic stimulation of a&#946; and tau levels in rhesus monkey cerebrospinal fluid
Uploaded: 2021-09-03T15:00:00
Description: Watch this Scientific Journal Video about A Pilot Study on the Repetitive Transcranial Magnetic Stimulation of AÃŽÂ² and Tau Levels in Rhesus Monkey Cerebrospinal Fluid at JoVE.com

作者要感谢四川绿屋生物科技有限公司提供的猴子椅和其他相关设备。这项研究没有得到公共，商业或非营利部门任何资助机构的具体资助。

所有实验均根据中华人民共和国科技部制定的《实验动物护理和使用指南》以及《巴塞尔宣言》的原则进行。四川大学华西医院动物护理委员会（中国成都）批准。 图1 显示了这里使用的单盲自控研究设计。
1. rTMS 设备
<ol><li>使用8形磁场刺激线圈执行rTMS刺激。</li>
</ol>2. 动物
<ol><li>将雄性恒河猴（玛卡卡穆拉塔，5公斤，5岁?...

<ol>
	<li>Niemantsverdriet, E., Valckx, S., Bjerke, M., Engelborghs, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alzheimer's+disease+CSF+biomarkers:+clinical+indications+and+rational+use.">Alzheimer's disease CSF biomarkers: clinical indications and rational use.</a> Acta Neurologica Belgica. 117 (3), 591-602 (2017).</li><li>Ohnishi, S., Takano, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Amyloid+fibrils+from+the+viewpoint+of+protein+folding.">Amyloid fibrils from the viewpoint of protein folding.</a> Cellular and Molecular Life Sciences. 61 (5), 511-524 (2004).</li><li>Hernandez, F., Avila, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tauopathies.">Tauopathies.</a> Cellular and Molecular Life Sciences. 64 (17), 2219-2233 (2007).</li><li>Ballard, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alzheimer's+disease.">Alzheimer's disease.</a> Lancet. 377 (9770), 1019-1031 (2011).</li><li>De Meyer, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnosis-independent+Alzheimer+disease+biomarker+signature+in+cognitively+normal+elderly+people.">Diagnosis-independent Alzheimer disease biomarker signature in cognitively normal elderly people.</a> Archives of Neurology. 67 (8), 949-956 (2010).</li><li>Jansen, W. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prevalence+of+cerebral+amyloid+pathology+in+persons+without+dementia:+a+meta-analysis.">Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.</a> JAMA. 313 (19), 1924-1938 (2015).</li><li>Iaccarino, H. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gamma+frequency+entrainment+attenuates+amyloid+load+and+modifies+microglia.">Gamma frequency entrainment attenuates amyloid load and modifies microglia.</a> Nature. 540 (7632), 230-235 (2016).</li><li>Martorell, A. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multi-sensory+gamma+stimulation+ameliorates+Alzheimer's-associated+pathology+and+improves+cognition.">Multi-sensory gamma stimulation ameliorates Alzheimer's-associated pathology and improves cognition.</a> Cell. 177 (2), 256-271 (2019).</li><li>Kobayashi, M., Pascual-Leone, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+magnetic+stimulation+in+neurology.">Transcranial magnetic stimulation in neurology.</a> Lancet Neurology. 2 (3), 145-156 (2003).</li><li>Post, A., Muller, M. B., Engelmann, M., Keck, M. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Repetitive+transcranial+magnetic+stimulation+in+rats:+evidence+for+a+neuroprotective+effect+in+vitro+and+in+vivo.">Repetitive transcranial magnetic stimulation in rats: evidence for a neuroprotective effect in vitro and in vivo.</a> European Journal of Neuroscience. 11 (9), 3247-3254 (1999).</li><li>Huang, Z., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Low-frequency+repetitive+transcranial+magnetic+stimulation+ameliorates+cognitive+function+and+synaptic+plasticity+in+APP23/PS45+mouse+model+of+Alzheimer's+disease.">Low-frequency repetitive transcranial magnetic stimulation ameliorates cognitive function and synaptic plasticity in APP23/PS45 mouse model of Alzheimer's disease.</a> Frontiers in Aging Neuroscience. 9, 292 (2017).</li><li>Tan, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Low-frequency+(1+Hz)+repetitive+transcranial+magnetic+stimulation+(rTMS)+reverses+Abeta(1-42)-mediated+memory+deficits+in+rats.">Low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) reverses Abeta(1-42)-mediated memory deficits in rats.</a> Experimental Gerontology. 48 (8), 786-794 (2013).</li><li>Bai, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Repetitive+transcranial+magnetic+stimulation+reverses+Abeta1-42-induced+dysfunction+in+gamma+oscillation+during+working+memory.">Repetitive transcranial magnetic stimulation reverses Abeta1-42-induced dysfunction in gamma oscillation during working memory.</a> Currrent Alzheimer Research. 15 (6), 570-577 (2018).</li><li>Heo, J. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spatial+distribution+of+glucose+hypometabolism+induced+by+intracerebroventricular+streptozotocin+in+monkeys.">Spatial distribution of glucose hypometabolism induced by intracerebroventricular streptozotocin in monkeys.</a> Journal of Alzheimers Disease. 25 (3), 517-523 (2011).</li><li>Lee, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Insulin/IGF+signaling-related+gene+expression+in+the+brain+of+a+sporadic+Alzheimer's+disease+monkey+model+induced+by+intracerebroventricular+injection+of+streptozotocin.">Insulin/IGF signaling-related gene expression in the brain of a sporadic Alzheimer's disease monkey model induced by intracerebroventricular injection of streptozotocin.</a> Journal of Alzheimers Disease. 38 (2), 251-267 (2014).</li><li>Zhang, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Temporal+analysis+of+blood-brain+barrier+disruption+and+cerebrospinal+fluid+matrix+metalloproteinases+in+rhesus+monkeys+subjected+to+transient+ischemic+stroke.">Temporal analysis of blood-brain barrier disruption and cerebrospinal fluid matrix metalloproteinases in rhesus monkeys subjected to transient ischemic stroke.</a> Journal of Cerebral Blood Flow and Metabolism. 37 (8), 2963-2974 (2017).</li><li>Liao, X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Repetitive+transcranial+magnetic+stimulation+as+an+alternative+therapy+for+cognitive+impairment+in+Alzheimer's+disease:+a+meta-analysis.">Repetitive transcranial magnetic stimulation as an alternative therapy for cognitive impairment in Alzheimer's disease: a meta-analysis.</a> Journal of Alzheimers Disease. 48 (2), 463-472 (2015).</li><li>Hwang, J. M., Kim, Y. H., Yoon, K. J., Uhm, K. E., Chang, W. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Different+responses+to+facilitatory+rTMS+according+to+BDNF+genotype.">Different responses to facilitatory rTMS according to BDNF genotype.</a> Clinical Neurophysiology. 126 (7), 1348-1353 (2015).</li><li>Uhm, K. E., Kim, Y. H., Yoon, K. J., Hwang, J. M., Chang, W. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=BDNF+genotype+influence+the+efficacy+of+rTMS+in+stroke+patients.">BDNF genotype influence the efficacy of rTMS in stroke patients.</a> Neuroscience Letters. 594, 117-121 (2015).</li><li>Ahmed, M. A., Darwish, E. S., Khedr, E. M., El Serogy, Y. M., Ali, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+low+versus+high+frequencies+of+repetitive+transcranial+magnetic+stimulation+on+cognitive+function+and+cortical+excitability+in+Alzheimer's+dementia.">Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer's dementia.</a> Journal of Neurology. 259 (1), 83-92 (2012).</li><li>Tan, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Low-frequency+(1+Hz)+repetitive+transcranial+magnetic+stimulation+(rTMS)+reverses+A&#946;(1-42)-mediated+memory+deficits+in+rats.">Low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) reverses A&#946;(1-42)-mediated memory deficits in rats.</a> Experimental Gerontology. 48 (8), 786-794 (2013).</li><li>Cotelli, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improved+language+performance+in+Alzheimer+disease+following+brain+stimulation.">Improved language performance in Alzheimer disease following brain stimulation.</a> Journal of Neurology Neurosurgery and Psychiatry. 82 (7), 794-797 (2011).</li><li>Dobrowolska, J. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=CNS+amyloid-beta,+soluble+APP-alpha+and+-beta+kinetics+during+BACE+inhibition.">CNS amyloid-beta, soluble APP-alpha and -beta kinetics during BACE inhibition.</a> Journal of Neuroscience. 34 (24), 8336-8346 (2014).</li><li>Sankaranarayanan, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=First+demonstration+of+cerebrospinal+fluid+and+plasma+A+beta+lowering+with+oral+administration+of+a+beta-site+amyloid+precursor+protein-cleaving+enzyme+1+inhibitor+in+nonhuman+primates.">First demonstration of cerebrospinal fluid and plasma A beta lowering with oral administration of a beta-site amyloid precursor protein-cleaving enzyme 1 inhibitor in nonhuman primates.</a> Journal of Pharmacology Experimental Therapeutics. 328 (1), 131-140 (2009).</li><li>Schoenfeld, H. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effect+of+angiotensin+receptor+neprilysin+inhibitor,+sacubitril/valsartan,+on+central+nervous+system+amyloid-beta+concentrations+and+clearance+in+the+cynomolgus+monkey.">The effect of angiotensin receptor neprilysin inhibitor, sacubitril/valsartan, on central nervous system amyloid-beta concentrations and clearance in the cynomolgus monkey.</a> Toxicology and Applied Pharmacology. 323, 53-65 (2017).</li><li>Blennow, K., Mattsson, N., Scholl, M., Hansson, O., Zetterberg, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Amyloid+biomarkers+in+Alzheimer's+disease.">Amyloid biomarkers in Alzheimer's disease.</a> Trends in Pharmacological Sciences. 36 (5), 297-309 (2015).</li><li>Janelidze, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=CSF+Abeta42/Abeta40+and+Abeta42/Abeta38+ratios:+better+diagnostic+markers+of+Alzheimer+disease.">CSF Abeta42/Abeta40 and Abeta42/Abeta38 ratios: better diagnostic markers of Alzheimer disease.</a> Annals of Clinical and Translational Neurology. 3 (3), 154-165 (2016).</li><li>Vogelgsang, J., Wedekind, D., Bouter, C., Klafki, H. W., Wiltfang, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reproducibility+of+Alzheimer's+disease+cerebrospinal+fluid-biomarker+measurements+under+clinical+routine+conditions.">Reproducibility of Alzheimer's disease cerebrospinal fluid-biomarker measurements under clinical routine conditions.</a> Journal of Alzheimers Disease. 62 (1), 203-212 (2018).</li><li>Dubois, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Advancing+research+diagnostic+criteria+for+Alzheimer's+disease:+the+IWG-2+criteria.">Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria.</a> Lancet Neurology. 13 (6), 614-629 (2014).</li><li>Schuff, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MRI+of+hippocampal+volume+loss+in+early+Alzheimer's+disease+in+relation+to+ApoE+genotype+and+biomarkers.">MRI of hippocampal volume loss in early Alzheimer's disease in relation to ApoE genotype and biomarkers.</a> Brain. 132, 1067-1077 (2009).</li><li>Stricker, N. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=CSF+biomarker+associations+with+change+in+hippocampal+volume+and+precuneus+thickness:+implications+for+the+Alzheimer's+pathological+cascade.">CSF biomarker associations with change in hippocampal volume and precuneus thickness: implications for the Alzheimer's pathological cascade.</a> Brain Imaging and Behavior. 6 (4), 599-609 (2012).</li><li>Cirrito, J. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synaptic+activity+regulates+interstitial+fluid+amyloid-beta+levels+in+vivo.">Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo.</a> Neuron. 48 (6), 913-922 (2005).</li><li>Duits, F. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Performance+and+complications+of+lumbar+puncture+in+memory+clinics:+Results+of+the+multicenter+lumbar+puncture+feasibility+study.">Performance and complications of lumbar puncture in memory clinics: Results of the multicenter lumbar puncture feasibility study.</a> Alzheimers &amp; Dementia. 12 (2), 154-163 (2016).</li><li>Engelborghs, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Consensus+guidelines+for+lumbar+puncture+in+patients+with+neurological+diseases.">Consensus guidelines for lumbar puncture in patients with neurological diseases.</a> Alzheimers Dement. 8, 111-126 (2017).</li><li>Costerus, J. M., Brouwer, M. C., van de Beek, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Technological+advances+and+changing+indications+for+lumbar+puncture+in+neurological+disorders.">Technological advances and changing indications for lumbar puncture in neurological disorders.</a> Lancet Neurology. 17 (3), 268-278 (2018).</li><li>Wang, Y. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cerebrospinal+fluid+leakage+and+headache+after+lumbar+puncture:+a+prospective+non-invasive+imaging+study.">Cerebrospinal fluid leakage and headache after lumbar puncture: a prospective non-invasive imaging study.</a> Brain. 138, 1492-1498 (2015).</li><li>Schmidt, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Detection+and+quantification+of+beta-amyloid,+pyroglutamyl+Abeta,+and+tau+in+aged+canines.">Detection and quantification of beta-amyloid, pyroglutamyl Abeta, and tau in aged canines.</a> Journal of Neuropathology and Experimental Neurology. 74 (9), 912-923 (2015).</li></ol>

Aβ1-42是AD的一种公认的生物标志物，是一种与大脑中Aβ代谢和淀粉样蛋白斑块形成相关的CSF核心生物标志物，已广泛应用于临床试验和临床26。最近的研究表明，CSF Aβ42 / Aβ40比率是AD的更好的诊断生物标志物，而不是单独的Aβ42，因为它是AD型病理学的更好指标27，28。Tau和pTau蛋白在神经退行过程中释放...

淀粉样蛋白β（Aβ）和tau是重要的脑脊液生物标志物。Aβ由42个氨基酸（Aβ1-42）组成，是经β和γ分泌酶水解的跨膜淀粉样蛋白前体蛋白（APP）的产物1。Aβ1-42 由于其溶解度特性，可能在大脑中聚集成细胞外淀粉样蛋白斑块1，2。Tau 是一种微管相关蛋白，主要存在于轴突中，参与顺行轴突转运3。异常的tau过度磷酸化主要是由激酶和磷酸酶之间的不平衡引起的，导致tau从微管中脱离并形成神经原纤维缠结（NFT）1。tau在脑脊液中的浓度增加，因为tau和磷酸化的tau蛋白（pTau）在神经退行过程中被释放到细胞外空间。先前的研究表明，脑脊液生物标志物与阿尔茨海默病（AD）大脑的三种主要病理变化有关：细胞外淀粉样蛋白斑块，细胞内NFT形成和神经元损失4。Aβ 和 tau 浓度异常出现在 AD 的早期阶段，因此可进行早期 AD 诊断5，6。
2016年，Tsai等人发现，非侵入性光闪烁（40 Hz）降低了预沉积小鼠视觉皮层中Aβ1-40 和Aβ1-42 的水平7。最近，他们进一步报告说，听觉音调刺激（40 Hz）改善了识别和空间记忆，降低了5XFAD小鼠海马体和听觉皮层（AC）中的淀粉样蛋白水平，并降低了P301S tauopathy模型8中的pTau浓度。这些结果表明，非侵入性技术可能会影响Aβ和tau代谢。
作为一种非侵入性工具，经颅磁刺激（TMS）可以电刺激神经组织，包括脊髓、周围神经和大脑皮层9。此外，它可以改变大脑皮层在受刺激部位和功能连接中的兴奋性。因此，TMS已被用于治疗神经退行性疾病以及预后和诊断测试。TMS中最常见的临床干预形式rTMS可以诱导皮层激活，改变皮层的兴奋性，并调节认知/运动功能。
据报道，20 Hz rTMS对包括谷氨酸和Aβ在内的氧化应激源具有 体外 神经保护作用，并改善了小鼠单克隆海马HT22细胞的整体活力10。在1 Hz rTMS刺激后，海马体中β位点APP切割酶1，APP及其C端片段显着减少。值得注意的是，海马CA1的长期增强，空间学习和记忆的损害被逆转11，12。Bai等人在工作记忆测试中研究了rTMS对Aβ诱导的γ振荡功能障碍的影响。他们得出结论，rTMS可以逆转Aβ诱导的功能障碍，从而对工作记忆产生潜在的益处13。然而，关于rTMS对tau代谢的影响以及rTMS前后脑脊液中Aβ和tau的动态变化的报道很少。该协议描述了在不同频率（低频，1 Hz;高频，20 Hz和40 Hz）下rTMS对恒河猴CSF中Aβ和tau水平的影响的程序。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Anesthesia Puncture Kit for Single Use</td>
			<td>Weigao, Shandong, China</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>CCY-I magnetic field stimulator</td>
			<td>YIRUIDE MEDICAL, Wuhan, China</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>GraphPad Prism version 7.0</td>
			<td>GraphPad Software, Inc., San Diego, CA, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Human Amyloid Beta and Tau Magnetic Bead Panel</td>
			<td>EMD Millipore Corporation, Billerica, MA 01821 USA</td>
			<td></td>
			<td>liquid chip detection</td>
		</tr>
		<tr>
			<td>MILLIPLEX Analyst 5.1</td>
			<td>EMD Millipore Corporation, Billerica, MA 01821 USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Monkey Chair HH-E-1</td>
			<td>Brainsight, Cambridge, MA 02140 USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Zoletil 50</td>
			<td>Virbac, France</td>
			<td></td>
			<td>zolazepam&#8211;tiletamine</td>
		</tr>
	</tbody>
</table>

a pilot study on the repetitive transcranial magnetic stimulation of a&#946; and tau levels in rhesus monkey cerebrospinal fluid

先前的研究表明，非侵入性闪烁的光和听觉音调刺激可能会影响大脑中的Aβ和tau代谢。作为一种非侵入性技术，重复经颅磁刺激（rTMS）已被应用于神经退行性疾病的治疗。本研究探讨了rTMS对恒河猴脑脊液（CSF）中Aβ和tau水平的影响。这是一项单盲、自我控制的研究。使用三种不同的频率（低频，1 Hz;高频，20 Hz和40 Hz）的rTMS来刺激恒河猴的双侧背外侧前额叶皮层（DLPFC）。使用导管插入术收集脑脊液。所有样品均进行液体芯片检测以分析CSF生物标志物（Aβ42，Aβ42 / Aβ40，tTau，pTau）。脑脊液生物标志物水平在rTMS刺激后随时间变化。刺激后，脑脊液中的Aβ42 水平在所有频率（1 Hz，20 Hz和40 Hz）下均呈上升趋势，高频（p<0.05）的差异比低频差异更大。 
高频rTMS后，脑脊液总Tau（tTau）水平在rTMS后时间点（p<0.05）立即升高，并逐渐下降24 h。此外，结果表明，磷酸化Tau（pTau）的水平在40 Hz rTMS（p<0.05）后立即增加。Aβ42/Aβ40 的比率在1 Hz和20 Hz时呈上升趋势（p<0.05）。低频（1 Hz）刺激的tau水平没有显着差异。因此，rTMS的高频（20 Hz和40 Hz）可能对恒河猴脑脊液中的Aβ和tau水平产生积极影响，而低频（1 Hz）rTMS只能影响Aβ水平。

结果表明，rTMS可以影响恒河猴脑脊液中的Aβ和tau水平。在不同频率（1 Hz，20 Hz和40 Hz）下进行rTMS刺激后，脑脊液生物标志物水平随时间变化。
Aβ42 和 Aβ42/Aβ40 如图4A所示，在1 Hz rTMS刺激后，Aβ42水平在24 h内逐渐升高（p<0.05），并在冲洗期后?...

Watch this Scientific Journal Video about A Pilot Study on the Repetitive Transcranial Magnetic Stimulation of AÃŽÂ² and Tau Levels in Rhesus Monkey Cerebrospinal Fluid at JoVE.com

A Pilot Study on the Repetitive Transcranial Magnetic Stimulation of AÃƒÅ½Ã‚Â² and Tau Levels in Rhesus Monkey Cerebrospinal Fluid

在这里，我们描述了一项试点研究的程序，以探索不同频率（1 Hz / 20 Hz / 40 Hz）的重复经颅磁刺激对恒河猴脑脊液中Aβ和tau代谢的影响。

恒河猴脑脊液中Aβ和Tau水平重复经颅磁刺激的试点研究

Previous studies have demonstrated that a non-invasive light-flickering regime and auditory tone stimulation could affect A&#946; and tau metabolism in ...

该协议使用连续大水池CSF采样方法来探索rTMS对恒河猴α-β和tau水平的影响。该技术使用一种新颖的脑脊液采样方法，允许在完全清醒的条件下重复脑脊液采样，不良事件的风险较低。演示该程序的将是西南医科大学生理学系的研究助理张英谦和四川大学研究生谭慧鑫。在给予镇痛并确认麻醉成功后，将五岁的雄性恒河猴放在手术台上，以侧卧位，并对下背部周围的区域进行消毒。驼背，将膝盖朝胸部。在腰椎L4至L5之间插入一根脊髓针，然后将其推入，直到有爆音表明进入腰椎囊箱，其中装有韧带黄韧带。继续进一步推动针头，直到出现第二次爆破声，表明进入硬脑膜，然后从脊柱针中取出针头并收集脑脊液滴。接下来，在透视引导下进行导管插入，方法是将硬膜外导管通过穿刺针插入蛛网膜下腔，直到它在大水池中浮力。然后进行移植植入，从穿刺部位向头部做一个五厘米的切口，并将皮肤与皮下组织隔离开来，以放置采样口。将端口连接到硬膜外导管的末端，将端口植入皮肤下并缝合切口。对于脑脊液收集，使用笼杆约束猴子并保持背部弯曲。然后用酒精棉签擦拭，并将注射器插入采样口的中心，通过导管从大蓄水池中提取脑脊液。丢弃前200微升脑脊液，然后收集一毫升脑脊液进行分析。实验前将猴子固定在猴子椅上，以避免在rTMS干预期间中断，然后在猴子清醒时收集CSF进行生物标志物分析，以避免麻醉药物的影响。在蛛网膜下腔导管插入术后的第三天和实验开始前两周，用猴子椅子进行适应性训练，每天两次，每次30分钟。在用猴子椅进行适应性训练后一周和正式实验开始前一周进行rTMS自适应训练或假刺激，以避免在刺激过程中受到振动和声音的阻碍实验进度。对于假刺激，请使用产生振动和声音但不产生磁场的假线圈。刺激后，向猴子提供食物，以帮助它适应这个过程。根据国际10至20系统定位双侧背外侧前额叶皮层，并使用三种不同的频率进行三次不同的rTMS疗程，冲刷期不超过24小时。连续三天每天进行两次第一次，第二次和第三次训练。要分析四种脑脊液生物标志物，请使用微创导管插入术来收集脑脊液。在五个时间点收集CSF，每个时间点以三分钟的间隔收集四个样本。在收集了三个频率的总共60个样品后，将它们编号并储存在零下80摄氏度的冰箱中长达一个月。实验结束后，根据制造商的说明对所有样品进行液体芯片检测。在一次赫兹rTMS刺激后，Abeta42水平在24小时内逐渐升高。与20赫兹的rTMS类似，Abeta42水平随着时间的推移而增加，并在刺激后六小时达到峰值。相反，在40赫兹刺激后，Abeta42水平在rTMS后的时间点立即显着增加，然后缓慢下降。使用1赫兹和20赫兹rTMS刺激后，Abeta42与Abeta40的比率呈上升趋势，并在刺激后两小时显着增加。然而，在40赫兹时，比率没有显着差异。脑脊液中的tTau水平在20和40赫兹rTMS刺激后立即升高并逐渐降低。然而，在一赫兹刺激后没有显着差异。pTau水平在40赫兹刺激后立即升高，24小时后降至基线水平以下。相比之下，对于1赫兹和20赫兹的刺激，pTau水平呈现下降趋势。需要多个猴子脑脊液样本的研究人员可以考虑这种连续的蓄水池大脑脊液采样方法。

Research

JoVE Journal

Neuroscience

A Pilot Study on the Repetitive Transcranial Magnetic Stimulation of A&#946; and Tau Levels in Rhesus Monkey Cerebrospinal Fluid

A Novel Approach for Documenting Phosphenes Induced by Transcranial Magnetic Stimulation

一个新颖的方法记录经颅磁刺激诱发幻视

Stimulation of the human visual cortex produces a transient perception of light, known as a phosphene. Phosphenes are induced by invasive electrical ...

科研

神经科学

Combining Transcranial Magnetic Stimulation and fMRI to Examine the Default Mode Network

结合经颅磁刺激和功能磁共振成像检查默认模式网络

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful ...

State-Dependency Effects on TMS:  A Look at Motive Phosphene Behavior

依赖国家对TMS的：一看动机幻视行为

Transcranial magnetic stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate ...

The Use of Magnetic Resonance Spectroscopy as a Tool for the Measurement of Bi-hemispheric Transcranial Electric Stimulation Effects on Primary Motor Cortex Metabolism

磁共振波谱的用途，用于对初级运动皮层新陈代谢双半球经颅电刺激效果的测量工具一

Transcranial direct current stimulation (tDCS) is a neuromodulation technique that has been increasingly used over the past decade in the treatment of ...

Effects of Transcranial Alternating Current Stimulation on the Primary Motor Cortex by Online Combined Approach with Transcranial Magnetic Stimulation

经颅磁刺激在线联合方法对经颅交流电刺激对原发性运动皮层的影响

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific ...

Sample Preparation for Endopeptidomic Analysis in Human Cerebrospinal Fluid

人脑脊液 Endopeptidomic 分析的样品制备

This protocol describes a method developed to identify endogenous peptides in human cerebrospinal fluid (CSF). For this purpose, a previously developed ...

Online Transcranial Magnetic Stimulation Protocol for Measuring Cortical Physiology Associated with Response Inhibition

在线经颅磁刺激测量与反应抑制相关的皮质生理

We describe the development of a reproducible, child-friendly motor response inhibition task suitable for online Transcranial Magnetic Stimulation (TMS) ...

Combined Transcranial Magnetic Stimulation and Electroencephalography of the Dorsolateral Prefrontal Cortex

侧前额叶皮质联合经颅磁刺激与脑电图的研究

Transcranial magnetic stimulation (TMS) is a non-invasive method that produces neural excitation in the cortex by means of brief, time-varying magnetic ...

Bilateral Assessment of the Corticospinal Pathways of the Ankle Muscles Using Navigated Transcranial Magnetic Stimulation

导航经颅磁刺激踝关节脊椎通路的双边评价

Distal leg muscles receive neural input from motor cortical areas via the corticospinal tract, which is one of the main motor descending pathway in humans ...

In Vivo Imaging of Cerebrospinal Fluid Transport through the Intact Mouse Skull using Fluorescence Macroscopy

使用荧光宏镜检查,通过"完整小鼠头骨"进行脑脊液传输的 Vivo 成像

Cerebrospinal fluid (CSF) flow in rodents has largely been studied using ex vivo quantification of tracers. Techniques such as two-photon microscopy and ...