Zhang Q, Shi T J, Ji R R, Zhang Y Z, Sundler F, Hannibal J, Fahrenkrug J, Hökfelt T
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Brain Res. 1995 Dec 24;705(1-2):149-58. doi: 10.1016/0006-8993(95)01150-1.
Pituitary adenylate cyclase-activating polypeptide (PACAP) has recently been demonstrated in sensory neurons. In the present study on rat 17.5% of all neurons, mainly of small size, contained PACAP in normal dorsal root ganglia (DRGs). Transection of the sciatic nerve induced a rapid and strong upregulation in PACAP peptide and mRNA levels which could be seen already after 15 h. After 3 days more than 51.5% of neurons of different sizes expressed PACAP. However, the intensity of PACAP-LI in the DRG neurons declined after 10 days. Thirty days after axotomy, 56.7% of the DRG neurons still expressed PACAP, but with a low intensity, in fact even lower than in normal controls. No VIP- or NPY-positive neurons were observed in normal or axotomized DRGs at 15 h. However a distinct increase in VIP and NPY levels were seen 3 days after the lesion, and their levels were considerably higher after 30 days. PACAP was often present in neurons expressing VIP, NPY and/or galanin. Thus, 3 days after injury, PACAP was present in 84.4%, 95.7%, and 76.8% of the VIP-, NPY-, and galanin-positive neurons, respectively. PACAP was also found in nerve fibers in control sciatic nerves. After nerve ligation, accumulation of PACAP was seen mainly proximal to the injury but also distally, suggesting both anterograde and retrograde transport of the peptide. Also a moderate increase (about 20%) in PACAP levels was found in the superficial spinal dorsal horn 3 days after nerve transection. Taken together, our results suggest that PACAP is involved in the response to nerve injury. The very high levels of expression in different populations of DRG neurons after axotomy, and its different time course as compared to galanin, NPY and VIP indicate that it may play a complementary and/or different role than these peptides in the adaptation to nerve injury, especially in its early phase.
垂体腺苷酸环化酶激活多肽（PACAP）最近在感觉神经元中被发现。在本项针对大鼠的研究中，正常背根神经节（DRG）中17.5%的神经元（主要是小尺寸神经元）含有PACAP。坐骨神经横断后，PACAP肽和mRNA水平迅速且强烈上调，在15小时后即可观察到。3天后，超过51.5%的不同大小的神经元表达PACAP。然而，DRG神经元中PACAP免疫反应性强度在10天后下降。轴突切断30天后，56.7%的DRG神经元仍表达PACAP，但强度较低，实际上甚至低于正常对照组。在15小时时，正常或轴突切断的DRG中未观察到VIP或NPY阳性神经元。然而，损伤3天后VIP和NPY水平明显升高，30天后它们的水平更高。PACAP常存在于表达VIP、NPY和/或甘丙肽的神经元中。因此，损伤3天后，PACAP分别存在于84.4%、95.7%和76.8%的VIP、NPY和甘丙肽阳性神经元中。在对照坐骨神经的神经纤维中也发现了PACAP。神经结扎后，PACAP的积累主要见于损伤部位近端，但也见于远端，提示该肽既有顺行运输也有逆行运输。神经横断3天后，脊髓背角浅层的PACAP水平也有适度升高（约20%）。综上所述，我们的结果表明PACAP参与了对神经损伤的反应。轴突切断后DRG神经元不同群体中PACAP的高表达水平，以及与甘丙肽、NPY和VIP相比其不同的时间进程，表明它在适应神经损伤，尤其是早期阶段，可能发挥与这些肽互补和/或不同的作用。
