Morphological Survey of L-DOPA Containing Neurons in the Central Nervous System.

酪氨酸羟化酶(TH)是儿茶酚胺合成的限速酶，它能将酪氨酸转化为L多巴。近年来，几个研究小组报道，不仅在众所周知的儿茶酚胺能神经元中检测到TH免疫反应，而且在非儿茶酚胺能神经元中也检测到TH免疫反应。在本研究中，我们用不敏感的免疫细胞化学方法研究了这些异位TH神经元，提出了其中一些神经元产生L-多巴的可能性。(1)观察了L-多巴免疫反应阳性神经元在大鼠下丘脑的免疫细胞化学分布及其摄取L-多巴的能力。在经典的多巴胺能细胞群(A11、A12、A13和A14)中可检测到弱的L-多巴酚丁胺免疫反应(IR)神经元。在弓状核的腹外侧部、脑腹面背侧的弓状核周围区(VLAR/PA)、下丘脑前部的脑室周围区和弓状核的尾侧部有较强的L-多巴-免疫反应阳性神经元。腹腔注射利血平(10 mg/kg)、外周氨基酸脱羧酶抑制剂(Ro4-4602)和L多巴(50 mg/kg)可诱导神经元内的多巴胺免疫反应，其分布与含有AADC的神经元的分布一致。然而，这些处理并不能在VLAR/PA中诱导出多巴胺免疫反应神经元。本研究结果提示，L多巴标记神经元的脱羧基活性为零或很低，进一步支持了这种神经元产生L多巴作为终末产物的假说。(2)在日本猕猴的下丘脑，非儿茶酚胺能的TH阳性神经元出现在室旁核的尾侧部和漏斗核的腹外侧部。(3)用大鼠TH的c DNA探针进行原位杂交研究，发现TH阳性细胞的分布模式与TH免疫阳性神经元相似。

Tyrosine hydroxylase (TH) is a rate-limiting enzyme for catecholamine synthesis, and it converts tyrosine to L-DOPA. In recent years, several groups of investigators have reported that TH-immunoreactivity is detleted not only in well-known catecholaminergic neurons but also in noncatecholaminergic neurons. In the present study, we investigated these ectopic TH neurons by asensitive immunocytochemical method, and presented the possibility that some of these neurons produce L-DOPA as an endproduct.(1) The immunocytochemical distribution of L-DOPA immunoreactive neurons and their ability to uptake L-DOPA were investigated in the rat hypothalamus. Weakly L-DOPA-immunoreactive (IR) neurons were detected in the classical dopaminergic cell groups (A11, A12, A13, and A14). Strongly L-DOPA-IR neurons were found in the ventrolateral part of the arcuate nucleus, periarcuate region just dorsal to the ventral surface of the brain (VLAR/PA), periventricular area of the anterior hypothalamus, and caudal part of the arcuate nucleus. Intraperitoneal treatment with reserpine (10 mg/kg), peripheric amino acid decarboxylase (AADC) inhibitor (Ro4-4602), and L-DOPA (50 mg/kg) induced dopamine immunoreactivity in neurons, which distribution was coincident with that of AADC-containing neurons. However, these treatments could not induce dopamine-IR neurons in VLAR/PA. The present finding suggests that the decarboxylating activity in strongly stained L-DOPA neurons is zero or very low, and further supports the hypothesis that these neurons produce L-DOPA as an end product.(2) In the hypothalamus of Japanese monkey (macaca fuscata), non-catecholaminergic TH-IR neurons were detected in the caudal part of the paraventricular nucleus and the ventrolateral part of the infundibular nucleus.(3) In in situ hybridization study using cDNA probes of rat TH, TH mRNA positive cells showed the similar distribution pattern of TH-IR neurons.