Yodlowski M L, Fredieu J R, Landis S C
J Neurosci. 1984 Jun;4(6):1535-48. doi: 10.1523/JNEUROSCI.04-06-01535.1984.
Previous studies of the development of cholinergic sympathetic innervation of sweat glands in rat footpads suggested that these terminals initially exhibit noradrenergic properties which are lost as the glands and their innervation mature. We have treated neonatal and adult rats with 6-hydroxydopamine (6-OHDA), a toxic congener of norepinephrine, and compared its effects on the cholinergic sympathetic innervation of sweat glands and the noradrenergic sympathetic innervation of the iris, salivary gland, and blood vessels. As reported by others, 6-OHDA treatment of neonates caused the destruction of noradrenergic fibers in the iris and salivary gland but did not affect other fibers projecting to these targets that stain for acetylcholinesterase (AChE). We found that 6-OHDA treatment of neonatal animals also caused the destruction of the sympathetic axons in immature sweat glands that possess catecholamine histofluorescence and tyrosine-hydroxylase-like immunoreactivity. Furthermore, when such animals were examined as adults, we found no AChE staining, vasoactive intestinal peptide (VIP)-like immunoreactivity, or characteristic sympathetic axonal varicosities. However, the denervated glands were invested by a plexus of sensory axons, some of which exhibited substance P-like immunoreactivity (SP-IR). An increase in the number of SP-IR fibers also occurred in the sympathetically denervated irides of these animals. Chronic treatment of neonates with guanethidine, another adrenergic sympathetic neurotoxin, resulted in similar loss of cholinergic sweat gland innervation. Treatment of adults rats with doses of 6-OHDA identical to those used to treat neonates caused the loss of noradrenergic fibers from the iris, salivary gland, and many blood vessels but did not noticeably affect AChE and VIP staining or axonal ultrastructure in the sweat glands. However, treatment with higher doses of 6-OHDA did cause significant axonal degeneration. The response of the sympathetic innervation of developing but not mature sweat glands to 6-OHDA provides evidence for a transition from noradrenergic to cholinergic phenotype during the development of sympathetic neurons in vivo similar to the transition observed in cell culture. The sprouting of sensory axons may be caused by NGF-like trophic influences present in some sympathetically denervated tissues.
以往对大鼠脚垫汗腺胆碱能交感神经支配发育的研究表明，这些终末最初表现出去甲肾上腺素能特性，随着腺体及其神经支配的成熟，这些特性会丧失。我们用去甲肾上腺素的毒性类似物6-羟基多巴胺（6-OHDA）处理新生大鼠和成年大鼠，并比较其对汗腺胆碱能交感神经支配以及虹膜、唾液腺和血管去甲肾上腺素能交感神经支配的影响。正如其他人所报道的，用6-OHDA处理新生大鼠会导致虹膜和唾液腺中去甲肾上腺素能纤维的破坏，但不影响投射到这些靶点且乙酰胆碱酯酶（AChE）染色阳性的其他纤维。我们发现，用6-OHDA处理新生动物也会导致未成熟汗腺中具有儿茶酚胺组织荧光和酪氨酸羟化酶样免疫反应性的交感轴突的破坏。此外，当将这些动物作为成年动物检查时，我们未发现AChE染色、血管活性肠肽（VIP）样免疫反应性或特征性的交感轴突膨体。然而，去神经支配的腺体被感觉轴突丛所包围，其中一些轴突表现出P物质样免疫反应性（SP-IR）。在这些动物的交感神经去支配的虹膜中，SP-IR纤维的数量也有所增加。用另一种肾上腺素能交感神经毒素胍乙啶长期处理新生大鼠，会导致胆碱能汗腺神经支配出现类似的丧失。用与处理新生大鼠相同剂量的6-OHDA处理成年大鼠，会导致虹膜、唾液腺和许多血管中去甲肾上腺素能纤维的丧失，但对汗腺中的AChE和VIP染色或轴突超微结构没有明显影响。然而，用更高剂量的6-OHDA处理确实会导致明显的轴突变性。发育中的但非成熟汗腺的交感神经支配对6-OHDA的反应，为体内交感神经元发育过程中从去甲肾上腺素能表型向胆碱能表型的转变提供了证据，这类似于在细胞培养中观察到的转变。感觉轴突的出芽可能是由一些交感神经去支配组织中存在的类神经生长因子营养影响所引起的。
