Dócs Klaudia, Hegyi Zoltán, Holló Krisztina, Kis Gréta, Hegedűs Krisztina, Antal Miklós
Department of Anatomy, Histology and Embryology, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, Nagyerdei krt 98, Debrecen, 4032, Hungary.
Brain Struct Funct. 2015 Sep;220(5):2625-37. doi: 10.1007/s00429-014-0813-x. Epub 2014 Jun 19.
The importance of 2-AG-mediated endogenous cannabinoid signaling in spinal pain control has recently been well substantiated. Although the degradation of 2-AG seems to be essential in cannabinoid-mediated spinal nociceptive information processing, no experimental data are available about the cellular distribution of monoacylglycerol lipase (MGL), the main degrading enzyme of 2-AG in the spinal dorsal horn. Thus, here we investigated the cellular distribution of MGL in laminae I-II of the spinal gray matter with immunocytochemical methods and revealed an abundant immunoreactivity for MGL in the rodent superficial spinal dorsal horn. We addressed the co-localization of MGL with markers of peptidergic and non-peptidergic primary afferents, axon terminals of putative glutamatergic and GABAergic spinal neurons, as well as astrocytic and microglial profiles, and we found that nearly 17 % of the peptidergic (immunoreactive for CGRP), a bit more than 10 % of the axon terminals of putative glutamatergic spinal neurons (immunoreactive for VGLUT2), and approximately 20 % of the astrocytic (immunoreactive for GFAP) profiles were immunolabeled for MGL. On the other hand, however, axon terminals of non-peptidergic (binding isolectin-B4) nociceptive primary afferents and putative inhibitory spinal neurons (immunoreactive for VGAT) as well as microglial (immunoreactive for CD11b) profiles showed negligible immunostaining for MGL. The results suggest that only nociceptive inputs arriving through a population of CGRP immunoreactive fibers are modulated by the spinal DGLα-MGL pathway. We also postulate that the DGLα-MGL signaling pathway may modulate spinal excitatory but not inhibitory neural circuits.
2-花生四烯酸甘油（2-AG）介导的内源性大麻素信号传导在脊髓疼痛控制中的重要性最近已得到充分证实。尽管2-AG的降解似乎在大麻素介导的脊髓伤害性信息处理中至关重要，但关于单酰甘油脂肪酶（MGL），即2-AG在脊髓背角的主要降解酶的细胞分布，尚无实验数据。因此，我们在此用免疫细胞化学方法研究了脊髓灰质I-II层中MGL的细胞分布，并揭示了啮齿动物脊髓背角浅层中MGL有丰富的免疫反应性。我们研究了MGL与肽能和非肽能初级传入神经标记物、假定的谷氨酸能和γ-氨基丁酸能脊髓神经元的轴突终末以及星形胶质细胞和小胶质细胞形态的共定位，发现近17%的肽能神经（对降钙素基因相关肽[CGRP]免疫反应）、略多于10%的假定谷氨酸能脊髓神经元的轴突终末（对囊泡谷氨酸转运体2[VGLUT2]免疫反应）以及约20%的星形胶质细胞（对胶质纤维酸性蛋白[GFAP]免疫反应）形态被MGL免疫标记。然而，另一方面，非肽能（结合异凝集素B4）伤害性初级传入神经和假定的抑制性脊髓神经元（对囊泡抑制性氨基酸转运体[VGAT]免疫反应）的轴突终末以及小胶质细胞（对CD11b免疫反应）形态对MGL的免疫染色可忽略不计。结果表明，只有通过一群CGRP免疫反应性纤维传入的伤害性输入受脊髓二酰甘油脂肪酶α-单酰甘油脂肪酶（DGLα-MGL）途径调节。我们还推测，DGLα-MGL信号通路可能调节脊髓兴奋性而非抑制性神经回路。
