Mitrofanis John, Ashkan Keyoumars, Wallace Bradley A, Benabid Alim-Louis
Department of Clinical Neurosciences, University of Joseph Fourier, Grenoble, France.
J Neurocytol. 2004 Jul;33(4):429-40. doi: 10.1023/B:NEUR.0000046573.28081.dd.
In view of the recent focus on the zona incerta (and surrounding regions) as a target for deep brain stimulation in patients with Parkinson Disease, we have explored incertal cyto and chemoarchitecture in normal and MPTP (methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated macaque monkeys. Brains were processed for routine tyrosine hydroxylase (TH), nitric oxide synthase (NOs), parvalbumin (Pv) and calbindin D 28k (Cal) immunocytochemistry, as well as for Nissl staining. We show four main sectors in the zona incerta, namely rostral, dorsal, ventral and caudal, each with a largely distinct cytoarchitecture. Each of the antibodies screened had signature distribution patterns across the zona incerta; TH+ cells were localised within the rostral sector, NOs+ cells were concentrated in the dorsal sector, Pv+ cells were found mainly in the ventral sector and Cal+ cells were distributed uniformly across all sectors. These patterns match closely those reported in non primates. We found no major differences in the distribution and shape of labelled cells in the zona incerta of MPTP-treated monkeys when compared to control. In conclusion, we report that the primate zona incerta shows considerable cyto and chemoarchitectonic heterogeneity; that it forms a nucleus with distinct sectors presumably associated with diverse functions--from generating arousal to shifting attention, and from controlling visceral activity to influencing posture and locomotion. These functions have been proposed for the zona incerta of non primates. Our results have clinical implications, in that deep brain stimulation of the zona incerta (or parts thereof) could manifest in signs and symptoms other than those associated with the motor system. Such clinical stimulations could well involve other systems, including those of arousal, attention and visceral control.
鉴于最近将未定带（及周边区域）作为帕金森病患者深部脑刺激靶点的研究重点，我们对正常和经1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的猕猴的未定带细胞结构和化学结构进行了探索。对大脑进行常规酪氨酸羟化酶（TH）、一氧化氮合酶（NOs）、小白蛋白（Pv）和钙结合蛋白D 28k（Cal）免疫细胞化学处理以及尼氏染色。我们在未定带中显示出四个主要区域，即嘴侧、背侧、腹侧和尾侧，每个区域在细胞结构上基本都有明显差异。所筛选的每种抗体在整个未定带都有独特的分布模式；TH阳性细胞位于嘴侧区域，NOs阳性细胞集中在背侧区域，Pv阳性细胞主要见于腹侧区域，Cal阳性细胞均匀分布于所有区域。这些模式与非灵长类动物中报道的模式非常吻合。与对照组相比，我们发现经MPTP处理的猴子未定带中标记细胞的分布和形状没有重大差异。总之，我们报告灵长类动物的未定带显示出相当大的细胞和化学结构异质性；它形成一个具有不同区域的核，推测这些区域与多种功能相关——从产生觉醒到转移注意力，从控制内脏活动到影响姿势和运动。这些功能也被认为存在于非灵长类动物的未定带中。我们的结果具有临床意义，即对未定带（或其部分区域）进行深部脑刺激可能会表现出与运动系统无关的体征和症状。这种临床刺激很可能涉及其他系统，包括觉醒、注意力和内脏控制等系统。
