Neurofisiopatologia, IRCCS Fondazione S Lucia, Roma, Italy.
Cell Death Dis. 2011 May 5;2(5):e154. doi: 10.1038/cddis.2011.35.
At odd with traditional views, effective sub-thalamic nucleus (STN) deep brain stimulation (DBS), in Parkinson's disease (PD) patients, may increase the discharge rate of the substantia nigra pars reticulata and the internal globus pallidus (GPi), in combination with increased cyclic guanosine monophosphate (cGMP) levels. How these changes affect the basal ganglia (BG) output to the motor thalamus, the crucial structure conveying motor information to cortex, is critical. Here, we determined the extracellular GABA concentration in the ventral anterior nucleus (VA) during the first delivery of STN-DBS (n=10) or following levodopa (LD) (n=8). Both DBS and subdyskinetic LD reversibly reduced (-30%) VA GABA levels. A significant correlation occurred between clinical score and GABA concentration. By contrast, only STN-DBS increased GPi cGMP levels. Hence, STN-ON and MED-ON involve partially different action mechanisms but share a common target in the VA. These findings suggest that the standard BG circuitry, in PD, needs revision as relief from akinesia may take place, during DBS, even in absence of reduced GPi excitability. However, clinical amelioration requires fast change of thalamic GABA, confirming, in line with the old model, that VA is the core player in determining thalamo-cortical transmission.
与传统观点相反，在帕金森病（PD）患者中，有效的丘脑底核（STN）深部脑刺激（DBS）可能会增加黑质网状部和内苍白球（GPi）的放电率，同时增加环鸟苷酸（cGMP）水平。这些变化如何影响基底节（BG）向运动丘脑的输出，而运动丘脑是将运动信息传递到皮层的关键结构，这一点至关重要。在这里，我们在 STN-DBS 的第一次传递（n=10）或左旋多巴（LD）后（n=8），确定了腹前核（VA）中的细胞外 GABA 浓度。DBS 和亚运动性 LD 都可可逆地降低（-30%）VA GABA 水平。临床评分与 GABA 浓度之间存在显著相关性。相比之下，只有 STN-DBS 增加了 GPi 的 cGMP 水平。因此，STN-ON 和 MED-ON 涉及部分不同的作用机制，但在 VA 中有共同的靶点。这些发现表明，在 PD 中，标准的 BG 回路需要修正，因为即使在 GPi 兴奋性降低的情况下，DBS 也可能会缓解运动不能。然而，临床改善需要快速改变丘脑 GABA，这与旧模型一致，即 VA 是决定丘脑皮质传递的核心因素。
