Long-Term Effects of Repetitive Transcranial Magnetic Stimulation on Markers for Neuroplasticity: Differential Outcomes in Anesthetized and Awake Animals

Long-Term Effects of Repetitive Transcranial Magnetic Stimulation on Markers for Neuroplasticity: Differential Outcomes in Anesthetized and Awake Animals
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DOI:
10.1523/jneurosci.6751-10.2011
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发表时间:
2011-05-18
影响因子:
5.3
通讯作者:
Zangen, Abraham
Zangen, Abraham
中科院分区:
医学1区
文献类型:
--
作者:
Gersner, Roman;Kravetz, Elena;Zangen, Abraham

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重复经颅磁刺激(rTMS)的长期影响与神经可塑性有关,但大多数生理学研究仅评估了刺激对神经化学标记物的直接影响。此外,尽管已知基线兴奋性状态在rTMS结果中起主要作用,但自发神经活动在超可塑性中的作用尚未研究。本研究的第一个目的是评估和比较高,低频rTMS的神经可塑性的标志物,如BDNF和AMPA受体的GluR 1亚基的长期影响。第二个目的是评估这些影响是否依赖于自发的神经活动,通过比较麻醉和清醒大鼠的rTMS诱导的神经化学变化。每天10次的高或低频率rTMS应用于大鼠大脑,3天后,BDNF,GluR 1和磷酸化GluR 1的水平进行了评估,在海马,边缘前皮质和纹状体。我们发现高频刺激对神经可塑性标记物产生了深远的影响;在清醒的动物中增加它们,而在麻醉的动物中减少它们。相比之下,低频刺激在两种状态下都不会对这些标记物产生显著的长期影响。这项研究强调了rTMS期间自发神经活动的重要性,并证明高频rTMS可以诱导对BDNF和GluR 1的长期影响,这可能是这种治疗在神经可塑性相关疾病中的临床益处的基础。
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.