Posted by Biome on 3rd March 2014
经颅磁刺激（TMS: Transcranial magnetic stimulation）被认为可以影响大脑神经电活动，而且对于治疗抑郁症有显著的疗效，并于2008年获得美国食品药品管理署（FDA）的使用批准。穿透力更强的深颅脑刺激被尝试应用于治疗更严重的神经系统疾病比如帕金森氏病，然而对于这种电磁刺激治疗方法的生物学机制知之甚少。有关抑郁症的成年神经再生学说认为抑郁症状的缓解伴随着成年海马齿状回的神经再生。最近发表在Molecular Brain 上的一篇研究探索了在啮齿类动物模式中深脑磁刺激（DMS: Deep-brain magnetic stimulation）对海马新生神经元以及对抑郁症相关指标的影响。
行为学实验表明对实验诱导抑郁的小鼠模型进行深脑磁刺激可以显著减轻其抑郁表型。而通过给小鼠照射伽马射线来杀死大脑海马内增殖的神经前体细胞则表明深脑磁刺激治疗抑郁的效果依赖于海马内的新生神经元。一个在抑郁状态下下调的基因MKP1在经过深脑磁刺激后的表达水平也得到了恢复。此外,电生理实验表明深脑磁刺激可以有效的在约束压力刺激的实验大鼠（一种社会心理压力模型）中恢复海马的突触可塑性―长时程增强（LTP: Long-term potentiation）水平。这一发现表明深脑磁刺激对神经可塑性有重要的调控作用。最后，研究者令人吃惊的发现深脑磁刺激可以改善神经发育类疾病瑞特综合症小鼠模型的焦虑相关表型，甚至延长其寿命。
Clues to how deep brain stimulation may alleviate depression
Posted by Biome on 3rd March 2014
Magnetic stimulation of the scalp is thought to influence neural activity of the brain and has been used in the successful treatment of depression, becoming approved for use in the US in 2008. More invasive deep brain magnetic stimulation (DMS) has also been used in patients with severe neuropsychiatric disorders, including Parkinson’s, however, the biological basis of electrostimulation as a therapeutic approach remains poorly understood. The adult neurogenesis hypothesis of depression suggests that recovery is marked by neural growth in the dentate gyrus of the hippocampus. A recent study in Molecular Brain now explores how DMS affects hippocampal neurons and other markers of depression in rodents.
Under microscopic examination of the hippocampus of wild type mice, Zilong Qiu from the Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China, and colleagues found that DMS treatment resulted in neural stem cell proliferation and promoted dendrite growth in both adult and senescent animals. These striking morphological findings are supplemented by data showing the upregulation of marker genes for neural activity, including the hippocampal Fgf1b gene that is known to be induced by electroconvulsive stimulation.
Additional behavioral studies found that DMS could rescue an experimentally induced depressed phenotype in mice ？C an effect that was shown to depend upon growth of new hippocampal neurons, by using gamma irradiation to experimentally knock out neural proliferation. Recovery under DMS treatment was accompanied by restoration of MKP-1, a gene that is dysregulated during depression. Furthermore, an electrophysiological study of rats undergoing restraint stress (a model for psychosocial stress) revealed a recovery of axonal long-term potentiation to non-depressed levels under DMS treatment. This latter finding, alongside the changes that were already demonstrated in neural gene activity, suggests that DMS plays a role in modulating synaptic plasticity. Lastly, DMS was shown to reverse the anxiety phenotype and, somewhat surprisingly, extend lifespan in a mouse model of the neurodevelopmental disorder, Rett syndrome.
The effect of DMS treatment on neuronal growth and activity, in the adult rodent hippocampus, provides a novel biological evidence base for electrostimulation that merits further investigation to help treat neuropsychiatric disorders. The observations that DMS reverses several molecular, physiological and behavioral correlates of depression in rodent models deepens our knowledge of the pathophysiology of depressive disease in particular, and strengthens support for the use of electrostimulation to treat depression in humans.