High levels of histidine decarboxylase in the striatum of mice and rats.

High levels of histidine decarboxylase in the striatum of mice and rats.
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DOI:
10.1016/j.neulet.2011.03.050
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发表时间:
2011-05-16
影响因子:
2.5
通讯作者:
Pittenger C
Pittenger C
中科院分区:
医学4区
文献类型:
--
作者:
Krusong K;Ercan-Sencicek AG;Xu M;Ohtsu H;Anderson GM;State MW;Pittenger C

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神经递质组胺产生于下丘脑后部的结节乳头核;这些神经元广泛投射到整个中枢神经系统。组氨酸脱羧酶(HDC)从组氨酸合成组胺;在大脑中,其mRNA仅在下丘脑后部表达。组胺受体在整个前脑中表达,包括皮质、海马和基底神经节,表明这些结构的功能性神经支配。我们研究了HDC蛋白在小鼠和大鼠解剖组织中的分布,预期它将反映下丘脑组胺能轴突投射的密度,从而定性地平行于已知的组胺受体分布。正如预期的那样,在下丘脑中发现了高水平的HDC蛋白。令人惊讶的是,它在小鼠纹状体中的水平非常高。HDC蛋白在皮质、海马和小脑中低10倍。使用HDC敲除小鼠证实了通过蛋白质印迹进行的HDC检测的特异性。在大鼠的纹状体中也发现了类似的高水平HDC蛋白。纹状体不,但是,含有组胺的显著升高,相对于其他前脑结构,我们证实了这一事实,使用HPLC。纹状体中HDC蛋白和组胺水平之间的这种差异表明基底神经节中的组胺代谢和神经传递可能具有独特的特征,其细节仍有待阐明。
The neurotransmitter histamine is produced in the tuberomamillary nucleus of the posterior hypothalamus; these neurons project broadly throughout central nervous system. Histidine decarboxylase (HDC) synthesizes histamine from histidine; in the brain, its mRNA is expressed exclusively in the posterior hypothalamus. Histamine receptors are expressed throughout the forebrain, including in cortex, hippocampus, and basal ganglia, suggesting functional innervation of these structures. We investigated the distribution of HDC protein in dissected tissue from mouse and rat, anticipating that it would reflect the density of hypothalamic histaminergic axonal projections and thus qualitatively parallel the known distribution of histamine receptors. HDC protein was found at high levels in hypothalamus, as anticipated. Surprisingly, it was found at comparably high levels in mouse striatum. HDC protein was 10-fold lower in cortex, hippocampus, and cerebellum. Specificity of HDC detection by Western blot was confirmed using HDC knockout mice. Similar high levels of HDC protein were found in dissected striatum from rat. Striatum does not, however, contain comparably elevated of histamine, relative to other forebrain structures; we confirmed this fact using HPLC. This discrepancy between HDC protein and histamine levels in the striatum suggests that histamine metabolism and neurotransmission in basal ganglia may have unique characteristics, the details of which remain to be elucidated.
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