Kowall N W, Quigley B J, Krause J E, Lu F, Kosofsky B E, Ferrante R J
Neurology Service, Massachusetts General Hospital, Boston 02114.
Regul Pept. 1993 Jul 2;46(1-2):174-85. doi: 10.1016/0167-0115(93)90028-7.
Substance P immunoreactivity is localized in discrete subsets of neurons in the human cerebral cortex and basal ganglia. In the normal human cerebral cortex, a subset of aspiny local circuit neurons in deep cortical layers and the cortical subplate contain preprotachykinin mRNA and substance P immunoreactive. These neurons, which contain NADPH diaphorase (NO synthase) activity, are strikingly depleted in Alzheimer's disease--in contrast to other local circuit neurons--suggesting that they may be an early target of the degenerative process. In the human basal ganglia, substance P immunoreactivity and mRNA are localized in a subset of spiny striatal neurons that project to the internal segment of the globus pallidus. These neurons are enriched in D1 dopamine receptors and dynorphin, and are calbindin and DARP 32 immunoreactive. A separate subset of aspiny striatal local circuit neurons also contain substance P immunoreactivity. Fiber and terminal staining is prominent in the matrix compartment of the ventromedial striatum and persists dorsally as a rim outlining patches that contain lesser amounts of immunoreactivity. Intense fiber and terminal staining is found in the pars reticulata of the substantia nigra. In Huntington's disease, substance P is depleted in the striatum in parallel with the dorsoventral gradient of neuronal loss. Terminal staining is progressively depleted in the pallidum and substantia nigra in tandem with striatal atrophy. Substance P receptor immunoreactivity, defined with two polyclonal antisera raised against synthetic peptides derived from the substance P receptor sequence, intensely labels a subset of large neurons in the nucleus basalis and striatum identical to neurons labeled with choline acetyltransferase and nerve growth factor receptor antibodies (although striatal cholinergic neurons do not contain nerve growth factor receptor immunoreactivity in the human). These cholinergic neurons resist degeneration in Huntington's disease but are sensitive to degeneration in Alzheimer's disease. Less intensely labeled neurons include pyramidal neurons in the hippocampal CA2 field, nonpyramidal neurons in CA1-4, pyramidal and nonpyramidal neurons in deep neocortical layers and in the cortical subplate. Substance P receptor immunoreactivity is not well defined in the human globus pallidus or substantia nigra.
P物质免疫反应性定位于人类大脑皮质和基底神经节的离散神经元亚群中。在正常人类大脑皮质中，深层皮质层和皮质下板中的一类无棘局部回路神经元含有前速激肽原mRNA和P物质免疫反应性。这些含有NADPH黄递酶（一氧化氮合酶）活性的神经元，与其他局部回路神经元相比，在阿尔茨海默病中显著减少，这表明它们可能是退化过程的早期靶点。在人类基底神经节中，P物质免疫反应性和mRNA定位于投射到苍白球内侧段的一类有棘纹状体神经元中。这些神经元富含D1多巴胺受体和强啡肽，且具有钙结合蛋白和DARP 32免疫反应性。另一类无棘纹状体局部回路神经元亚群也含有P物质免疫反应性。纤维和终末染色在腹内侧纹状体的基质区很明显，并在背侧持续存在，形成一个勾勒出免疫反应性较低的斑块的边缘。在黑质网状部发现强烈的纤维和终末染色。在亨廷顿病中，P物质在纹状体中与神经元损失的背腹梯度平行减少。随着纹状体萎缩，苍白球和黑质中的终末染色逐渐减少。用针对P物质受体序列衍生的合成肽产生的两种多克隆抗血清所定义的P物质受体免疫反应性，强烈标记基底核和纹状体中的一类大神经元，这些神经元与用胆碱乙酰转移酶和神经生长因子受体抗体标记的神经元相同（尽管在人类中纹状体胆碱能神经元不含有神经生长因子受体免疫反应性）。这些胆碱能神经元在亨廷顿病中抵抗退化，但在阿尔茨海默病中对退化敏感。标记强度较低的神经元包括海马CA2区的锥体细胞、CA1 - 4区的非锥体细胞、深层新皮质层和皮质下板中的锥体细胞和非锥体细胞。在人类苍白球或黑质中，P物质受体免疫反应性不明确。
