C-JUN-like immunoreactivity in the CNS of the adult rat: Basal and transynaptically induced expression of an immediate-early gene

Abstract

An immunocytochemical study of dorsal root ganglia, spinal cord and medulla oblongata was performed with antisera against the c-jun proto-oncogene encoded protein. The c-JUN-like immunoreactivity was restricted to the cell nucleus. In the CNS of untreated rats a basal c-JUN-like immunoreactivity was present in the nuclei of two types of neurons: motor and autonomic. Labelled nuclei could be seen in many motoneurons of the ventral horn of the entire length of spinal cord and the lower medulla oblongata, as well as in the area of the nucleus hypoglossus, the dorsal motor nucleus of nucleus vagus, nucleus ambiguus, nucleus facialis, nucleus abducens and motor nucleus of nucleus trigeminus. Additionally, labelled nuclei were found in the preganglionic sympathetic and preganglionic parasympathetic cells of the nucleus intermediolateralis and nucleus intercalatus in the spinal cord. In the medulla oblongata we found a cluster of cells with c-JUN-like immunoreactivity in an area between the dorsomedial part of the oral nucleus spinalis trigeminalis and the lateral border of the knee of facial nerve. Additionally, a second cluster of c-JUN-like immunoreactivity cells was visible between the ventromedial part of the oral nucleus spinalis trigeminalis and the lateral border of the rostral nucleus facialis. Examination of the characteristics of all cell groups with a basal c-JUN-like immunoreactivity in the spinal cord and lower brainstem revealed an overlapping distribution with cholinergic cell groups. Basal c-JUN-like immunoreactivity was also seen in the dorsal root ganglion cells. We examined the factors which can effect the expression of the c-JUN protein. Maximal expression of c-JUN-like immunoreactivity was observed after electrical stimulation of primary afferents. Stimulation of sciatic nerve at a strength sufficient to recruit Aδ- and C-fibres produced c-JUN-like immunoreactivity in many nuclei of the ipsilateral dorsal horn of the lumbar spinal cord. c-JUN-like immunoreactivity was first detectable at 30 min following the end of stimulation, reached a maximum after 1 h, remained unchanged for another l h and declined to the basal level after 16h. The distribution of c-JUN-like immunoreactivity in the lumbar cord coincided with the region of termination of sciatic nociceptive afferents. Contralateral c-JUN-like immunoreactivity appeared after 4h. After noxious mechanical stimulation of the plantar hindpaw c-JUN-like immunoreactivity occurred in the spinal area of termination of nociceptive afferents of the tibial nerve. Noxious stimulation did not provoke additional c-JUN-like immunoreactivity in dorsal root ganglia. Electrical stimulation of large myelinated Aα/β-fibres of sciatic nerve and non-noxious stimulation of peripheral sensory nerve receptors was not effective for induction of c-JUN-like immunoreactivity in spinal neurons. This is the first study demonstrating the expression c-JUN protein in vivo, a transcriptional operating protein with a functional relation to the extensively studied c-FOS protein. Our data demonstrate a basal constitutive expression of c-JUN in CNS of normal adult rat which is not paralleled by the expression of c-FOS protein, thus indicating a fundamental selective expression of these functionally related proteins. Furthermore, we reveal for the first time that transient expression of immediate early genes in spinal cord is a neurogenic consequence during nociception which is dependent upon the activation of nociceptive primary afferents.