Chen L W, Wei L C, Lang B, Ju G, Chan Y S
Institute of Neuroscience, The Fourth Military Medical University, Xi'an 710032, PR China.
Neuroscience. 2001;106(1):149-60. doi: 10.1016/s0306-4522(01)00255-x.
We have examined the distribution of dopamine neurons expressing alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor subunits (glutamate receptors 1, 2/3 and 4) in the A8-A15 regions of the rat brain using double immunofluorescence. The distribution of glutamate receptor 1- or 2/3-like immunoreactive neurons completely overlapped that of tyrosine hydroxylase-like immunoreactive neurons in dopamine cell groups in the retrorubral field (A8), the substantia nigra (A9), the ventral tegmental area and the nucleus raphe linealis (A10), and the rostral hypothalamic periventricular nucleus (A14, A15). In the caudal hypothalamic periventricular nucleus (A11), arcuate nucleus (A12) and zona incerta (A13), the distribution was partially overlapping. Neurons double-labeled for tyrosine hydroxylase and glutamate receptor 1 or 2/3 immunoreactivities were, however, exclusively found in certain dopamine cell regions: in areas A14-A15, 85-88% of tyrosine hydroxylase-containing neurons expressed glutamate receptor 1 and 22-25% expressed glutamate receptor 2/3, while in areas A8-A10, 20-43% expressed glutamate receptor 1 and 63-84% expressed glutamate receptor 2/3. In contrast, the double-labeled neurons were hardly detected in the A11-A13 regions. No tyrosine hydroxylase-positive neurons displayed glutamate receptor 4 immunoreactivity, though a partially overlapping distribution of tyrosine hydroxylase- and glutamate receptor 4-immunopositive neurons was also seen in regions A8-10, A11 and A13. The present study has demonstrated the morphological evidence for direct modulation of dopamine neurons via AMPA receptors in rat mesencephalon and hypothalamus. This distribution may provide the basis for a selective dopamine neuron loss in neurodegenerative disorders, such as Parkinson's disease.
我们利用双重免疫荧光法检测了大鼠脑A8 - A15区域中表达α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体亚基（谷氨酸受体1、2/3和4）的多巴胺能神经元的分布情况。在红核后区（A8）、黑质（A9）、腹侧被盖区和中缝线性核（A10）以及下丘脑室周核前部（A14、A15）的多巴胺能细胞群中，谷氨酸受体1或2/3样免疫反应性神经元的分布与酪氨酸羟化酶样免疫反应性神经元的分布完全重叠。在尾侧下丘脑室周核（A11）、弓状核（A12）和未定带（A13）中，分布部分重叠。然而，酪氨酸羟化酶和谷氨酸受体1或2/3免疫反应性双重标记的神经元仅在某些多巴胺能细胞区域被发现：在A14 - A15区域，85 - 88%含酪氨酸羟化酶的神经元表达谷氨酸受体1，22 - 25%表达谷氨酸受体2/3，而在A8 - A10区域，20 - 43%表达谷氨酸受体1，63 - 84%表达谷氨酸受体2/3。相比之下，在A11 - A13区域几乎检测不到双重标记的神经元。虽然在A8 - 10、A11和A13区域也观察到酪氨酸羟化酶和谷氨酸受体4免疫阳性神经元的部分重叠分布，但没有酪氨酸羟化酶阳性神经元显示谷氨酸受体4免疫反应性。本研究为通过AMPA受体直接调节大鼠中脑和下丘脑的多巴胺能神经元提供了形态学证据。这种分布可能为神经退行性疾病（如帕金森病）中多巴胺能神经元的选择性丢失提供基础。
