發(fā)布時(shí)間：2014-03-10
深腦刺激可能減輕抑郁癥狀的證據(jù)(仇子龍）
Posted by Biome on 3rd March 2014
經(jīng)顱磁刺激（TMS: Transcranial magnetic stimulation）被認(rèn)為可以影響大腦神經(jīng)電活動(dòng)，而且對(duì)于治療抑郁癥有顯著的療效，并于2008年獲得美國食品藥品管理署（FDA）的使用批準(zhǔn)。穿透力更強(qiáng)的深顱腦刺激被嘗試應(yīng)用于治療更嚴(yán)重的神經(jīng)系統(tǒng)疾病比如帕金森氏病，然而對(duì)于這種電磁刺激治療方法的生物學(xué)機(jī)制知之甚少。有關(guān)抑郁癥的成年神經(jīng)再生學(xué)說認(rèn)為抑郁癥狀的緩解伴隨著成年海馬齒狀回的神經(jīng)再生。最近發(fā)表在Molecular Brain 上的一篇研究探索了在嚙齒類動(dòng)物模式中深腦磁刺激（DMS: Deep-brain magnetic stimulation）對(duì)海馬新生神經(jīng)元以及對(duì)抑郁癥相關(guān)指標(biāo)的影響。
來自中國科學(xué)院上海生命科學(xué)研究院的仇子龍研究員領(lǐng)導(dǎo)的研究團(tuán)隊(duì)，通過對(duì)野生型小鼠進(jìn)行顯微水平的檢測發(fā)現(xiàn)深腦磁刺激可以促進(jìn)成年及老年小鼠神經(jīng)干細(xì)胞增殖并且促進(jìn)成年海馬新生神經(jīng)元樹突發(fā)育。這些令人震驚的神經(jīng)元形態(tài)改變伴隨著電活動(dòng)誘導(dǎo)基因表達(dá)的上調(diào)，包括會(huì)被電擊療法激活的成纖維生長因子fgf1b基因等。
行為學(xué)實(shí)驗(yàn)表明對(duì)實(shí)驗(yàn)誘導(dǎo)抑郁的小鼠模型進(jìn)行深腦磁刺激可以顯著減輕其抑郁表型。而通過給小鼠照射伽馬射線來殺死大腦海馬內(nèi)增殖的神經(jīng)前體細(xì)胞則表明深腦磁刺激治療抑郁的效果依賴于海馬內(nèi)的新生神經(jīng)元。一個(gè)在抑郁狀態(tài)下下調(diào)的基因MKP1在經(jīng)過深腦磁刺激后的表達(dá)水平也得到了恢復(fù)。此外,電生理實(shí)驗(yàn)表明深腦磁刺激可以有效的在約束壓力刺激的實(shí)驗(yàn)大鼠（一種社會(huì)心理壓力模型）中恢復(fù)海馬的突觸可塑性―長時(shí)程增強(qiáng)（LTP: Long-term potentiation）水平。這一發(fā)現(xiàn)表明深腦磁刺激對(duì)神經(jīng)可塑性有重要的調(diào)控作用。最后，研究者令人吃驚的發(fā)現(xiàn)深腦磁刺激可以改善神經(jīng)發(fā)育類疾病瑞特綜合癥小鼠模型的焦慮相關(guān)表型，甚至延長其壽命。
深腦磁刺激對(duì)成年嚙齒類動(dòng)物海馬神經(jīng)生長以及電活動(dòng)的調(diào)節(jié)作用，為電磁刺激的治療提供了新的生物學(xué)依據(jù)，促進(jìn)更多對(duì)電磁刺激的研究進(jìn)而幫助治療神經(jīng)精神類疾病。深腦磁刺激在嚙齒類動(dòng)物抑郁模型中的分子、生理學(xué)以及行為學(xué)的研究結(jié)果加深了我們對(duì)抑郁癥的病理學(xué)了解，特別為電磁刺激對(duì)人類抑郁癥的治療提供強(qiáng)有力的支持證據(jù)。
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.
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