An evaluation of neuroplasticity and behavior after deep brain stimulation of the nucleus accumbens in an animal model of depression.
An evaluation of neuroplasticity and behavior after deep brain stimulation of the nucleus accumbens in an animal model of depression.
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DOI：
10.1227/neu.0b013e3182237346
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发表时间：
2011-12
期刊：
影响因子：
4.8
通讯作者：
Van Bockstaele EJ
中科院分区：
文献类型：
--
作者：
Falowski SM;Sharan A;Reyes BA;Sikkema C;Szot P;Van Bockstaele EJ
最近的兴趣已经证明了延髓核（NAcc）作为脑深部电刺激（DBS）治疗抑郁症的潜在靶点。证明NAcc的DBS是抑郁症的有效治疗方式，并且与这些行为变化相关的化学和结构变化是神经可塑性的标志。将深部脑刺激器放置在雄性Wistar-Kyoto大鼠的NAcc中。各组分为假手术组（无刺激）、间歇组（3 h/d，持续2周）和连续组（持续刺激2周）。在刺激前和刺激后，用旷场试验评价探索行为和焦虑样行为。前额叶皮质（PFC）的组织样本进行处理与去甲肾上腺素能活性，包括去甲肾上腺素能合成酶酪氨酸羟化酶的标志物的Western印迹分析。用高效液相色谱法分析组织中的儿茶酚胺水平。Golgi-Cox染色观察皮质锥体神经元的形态学特征。受试者接受间歇性和连续刺激的NAcc表现出增加的探索行为和减少焦虑样行为。酪氨酸羟化酶的表达水平降低PFC后，间歇性和连续DBS，多巴胺和去甲肾上腺素水平下降后，连续刺激。Golgi-Cox染色表明，DBS增加了PFC的锥体神经元的顶端和基底树突的长度。脑深部电刺激诱导PFC的行为改善和神经化学和形态学改变，表现出不同的刺激目标区域的大脑电路内的变化。这种观察到的树突可塑性可能是这种治疗的疗效的基础。
Recent interest has demonstrated the nucleus accumbens (NAcc) as a potential target for the treatment of depression with deep brain stimulation (DBS). To demonstrate that DBS of the NAcc is an effective treatment modality for depression and that chemical and structural changes associated with these behavioral changes are markers of neuroplasticity. A deep brain stimulator was placed in the NAcc of male Wistar-Kyoto rats. Groups were divided into sham (no stimulation), intermittent (3 h/d for 2 weeks), or continuous (constant stimulation for 2 weeks). Exploratory and anxietylike behaviors were evaluated with the open-field test before and after stimulation. Tissue samples of the prefrontal cortex (PFC) were processed with Western blot analysis of markers of noradrenergic activity that included the noradrenergic synthesizing enzyme tyrosine hydroxylase. Analysis of tissue levels for catecholamines was achieved with high-performance liquid chromatography. Morphological properties of cortical pyramidal neurons were assessed with Golgi-Cox staining. Subjects undergoing intermittent and continuous stimulation of the NAcc exhibited an increase in exploratory behavior and reduced anxietylike behaviors. Tyrosine hydroxylase expression levels were decreased in the PFC after intermittent and continuous DBS, and dopamine and norepinephrine levels were decreased after continuous stimulation. Golgi-Cox staining indicated that DBS increased the length of apical and basilar dendrites in pyramidal neurons of the PFC. Deep brain stimulation induces behavioral improvement in and neurochemical and morphological alterations of the PFC that demonstrate changes within the circuitry of the brain different from the target area of stimulation. This observed dendritic plasticity may underlie the therapeutic efficacy of this treatment.