Zhou X, Rodriguez W I, Casillas R A, Ma V, Tam J, Hu Z, Lelievre V, Chao A, Waschek J A
Department of Psychiatry and Mental Retardation Research Center, University of California at Los Angeles, Neuropsychiatric Institute, Los Angeles 90024, USA.
J Neurosci Res. 1999 Sep 15;57(6):953-61.
It has been demonstrated that pituitary adenylate cyclase activating polypeptide (PACAP) promotes the survival of neurons in culture and can inhibit neuronal cell death after experimental injury. Furthermore, peripheral axotomy results in increased PACAP gene expression in sensory and sympathetic neurons, suggesting that PACAP might be a mediator in the injury response in certain parts of the nervous system. However, changes in PACAP expression have not been reported in injured motor neurons, despite the significant problem of motor neuron degeneration in injury and in several neurological diseases. We examined here changes in gene expression of PACAP and two high-affinity PACAP receptors, PAC(1) and VPAC(2), in adult rat motor neurons after facial nerve axotomy by in situ hybridization. PACAP gene expression was very low in facial motor neurons of normal rats. However, a robust time-dependent increase in PACAP mRNA was observed in the facial motor nucleus in most or all axotomized motor neurons. This induction was detectable 6 hr after axotomy, and peaked at 48 hr, when expression on the injured side averaged more than 20-fold higher than that on the contralateral side. Thereafter, PACAP mRNA levels decreased slightly, but remained more than 10-fold elevated for as long as 30 days after axotomy. In contrast to PACAP, gene expression for both the PAC(1) and VPAC(2) receptor was high in facial motor neurons of normal rats. No significant change was observed for VPAC(2) receptor gene expression in facial motor neurons after axotomy, whereas gene expression for the PAC(1) receptor became significantly decreased. The results indicate that the PACAP ligand receptor system is tightly regulated in the facial motor nucleus after axotomy, providing evidence that PACAP may be involved in motor injury responses.
已证实垂体腺苷酸环化酶激活多肽（PACAP）可促进培养的神经元存活，并能抑制实验性损伤后的神经元细胞死亡。此外，外周轴突切断术会导致感觉神经元和交感神经元中PACAP基因表达增加，这表明PACAP可能是神经系统某些部位损伤反应的介质。然而，尽管在损伤和几种神经疾病中运动神经元变性是一个重大问题，但尚未有关于损伤的运动神经元中PACAP表达变化的报道。我们在此通过原位杂交研究了成年大鼠面神经切断术后运动神经元中PACAP及其两种高亲和力PACAP受体PAC(1)和VPAC(2)的基因表达变化。正常大鼠的面神经运动神经元中PACAP基因表达非常低。然而，在大多数或所有切断轴突的运动神经元的面神经运动核中，观察到PACAP mRNA呈强烈的时间依赖性增加。这种诱导在轴突切断后6小时即可检测到，并在48小时达到峰值，此时损伤侧的表达平均比对侧高20倍以上。此后，PACAP mRNA水平略有下降，但在轴突切断后长达30天内仍保持升高10倍以上。与PACAP相反，正常大鼠面神经运动神经元中PAC(1)和VPAC(2)受体的基因表达都很高。轴突切断后，面神经运动神经元中VPAC(2)受体基因表达未观察到显著变化，而PAC(1)受体的基因表达则显著降低。结果表明，轴突切断后面神经运动核中PACAP配体受体系统受到严格调控，这为PACAP可能参与运动损伤反应提供了证据。
