D'Ascanio P, Arrighi P, Pompeiano O
Dipartimento di Fisiologia e Biochimica, Università di Pisa, Italy.
Arch Ital Biol. 1998 Mar;136(2):83-102.
c-Fos mRNA and the related Fos-protein are rapidly induced by physiological stimuli and can be used as molecular markers of neural activation and plasticity. In a recent study (14), we found that rats submitted to unilateral labyrinthectomy (UL) displayed an asymmetric increase in the expression of both c-fos and Fos-protein not only in several vestibular, precerebellar and cerebellar structures and the caudate-putamen, but also in the locus coeruleus (LC)-complex, whose neurons integrate labyrinthine signals and are apparently involved in the plastic changes which are at the basis of vestibular compensation. In the present study we investigated the putative noradrenergic nature of the Fos-positive LC neurons observed after UL by combining Fos-protein immunocytochemistry with the immunocytochemical detection of tyrosine hydroxylase (TH), a synthetizing enzyme of noradrenaline. The experiments were performed in rats sacrificed 3, 6 and 24 h after surgical lesion of one labyrinth. The results obtained were in agreement with the previous findings, showing that already 3 h after UL an asymmetric increase of the c-fos and/or Fos-protein expression occurred in the vestibular nuclei, the inferior olive, the cerebellar cortex and the caudate-putamen. Most interestingly, the Fos-protein expression markedly increased in the LC-complex of both sides, although mainly ipsilaterally to the intact side. It appeared also that several Fos-positive LC-complex neurons were probably noradrenergic in nature, as they could be double-labeled with the Fos/TH technique. These findings were attenuated 6 h after UL and disappeared after 24 h, when partial compensation of the vestibular syndrome had occurred. Thus, UL results in asymmetric functional activation in the LC region of well identified noradrenergic neurons. This finding is attributed to the fact that asymmetric stimulation of labyrinth receptors gives rise to asymmetric changes in firing rate of LC neurons (45). Since these neurons send noradrenergic afferents to several target structures such as the vestibular nuclei, the inferior olive, the cerebellar cortex and the caudate-putamen, we postulated that the asymmetric labyrinthine activation of the noradrenergic LC system, occurring after UL, could increase the Fos-protein expression in the above mentioned brain structures. This possibility could then represent a key factor in determining the plastic changes, which are at the basis of vestibular compensation.
c-Fos信使核糖核酸（mRNA）及相关的Fos蛋白可被生理刺激迅速诱导，可用作神经激活和可塑性的分子标记物。在最近一项研究（14）中，我们发现接受单侧迷路切除术（UL）的大鼠不仅在几个前庭、小脑前和小脑结构以及尾状核 - 壳核中，而且在蓝斑（LC）复合体中，c-fos和Fos蛋白的表达均出现不对称增加，该复合体的神经元整合迷路信号，显然参与了作为前庭代偿基础的可塑性变化。在本研究中，我们通过将Fos蛋白免疫细胞化学与酪氨酸羟化酶（TH，去甲肾上腺素的合成酶）的免疫细胞化学检测相结合，研究了UL后观察到的Fos阳性LC神经元的假定去甲肾上腺素能性质。实验在一侧迷路手术损伤后3、6和24小时处死的大鼠中进行。获得的结果与先前的发现一致，表明UL后仅3小时，前庭核、下橄榄核、小脑皮质和尾状核 - 壳核中就出现了c-fos和/或Fos蛋白表达的不对称增加。最有趣的是，两侧LC复合体中Fos蛋白表达均显著增加，尽管主要在完整侧的同侧。似乎一些Fos阳性LC复合体神经元可能本质上是去甲肾上腺素能的，因为它们可以用Fos/TH技术进行双重标记。这些发现在UL后6小时减弱，并在24小时后消失，此时前庭综合征已部分代偿。因此，UL导致已明确的去甲肾上腺素能神经元的LC区域出现不对称功能激活。这一发现归因于迷路感受器的不对称刺激导致LC神经元放电率出现不对称变化（45）。由于这些神经元向几个靶结构如前庭核、下橄榄核、小脑皮质和尾状核 - 壳核发送去甲肾上腺素能传入纤维，我们推测UL后发生的去甲肾上腺素能LC系统的不对称迷路激活可能会增加上述脑结构中Fos蛋白的表达。这种可能性可能是决定作为前庭代偿基础的可塑性变化的关键因素。
