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，它将酪氨酸转化为L-DOPA。近年来，一些研究者报道TH免疫反应不仅存在于已知的儿茶酚胺能神经元，而且也存在于非儿茶酚胺能神经元。本研究用免疫细胞化学方法对这些异位TH神经元进行了研究，并提出了其中一些神经元产生L-DOPA作为终产物的可能性。(1)本文观察了大鼠下丘脑内左旋多巴（L-DOPA）免疫反应神经元的分布及其摄取L-DOPA的能力。在经典多巴胺能细胞组（A11、A12、A13和A14）中检测到弱L-DOPA免疫反应（IR）神经元。在弓状核腹外侧部、弓状核腹侧背侧区（VLAR/PA）、下丘脑前部室周区和弓状核尾侧部均发现L-DOPA阳性神经元。腹腔注射利血平（10 mg/kg）、外周氨基酸脱羧酶（AADC）抑制剂（Ro 4 -4602）和左旋多巴（50 mg/kg）可诱导多巴胺在神经元中的免疫反应，其分布与含AADC神经元的分布一致。然而，这些处理不能诱导VLAR/PA中的多巴胺-IR神经元。本研究结果表明，在强染色的L-DOPA神经元的脱羧活性为零或非常低，并进一步支持的假设，这些神经元产生L-DOPA作为最终产物。(2)在日本猕猴（macacafuscata）下丘脑，室旁核尾侧部和漏斗核腹外侧部有非儿茶酚胺能TH-IR神经元。(3)用大鼠TH的cDNA探针进行原位杂交研究，TH mRNA阳性细胞显示出与TH IR神经元相似的分布模式。

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.