Ciliary neurotrophic factor receptor alpha-immunoreactivity in the monkey central nervous system.

Abstract

Ciliary neurotrophic factor (CNTF) sustains the viability and phenotypic expression of a variety of neuronal populations in the central nervous system. Cranial and spinal motor neurons are particularly sensitive to the trophic effects of CNTF, and clinical trials are underway testing the potential therapeutic value of this trophic factor in patients with amyotrophic lateral sclerosis. Yet, the distribution of the alpha subunit of the receptor for ciliary neurotrophic factor (CNTFR alpha), which is essential for the trophic effects of CNTF to occur, is unknown in any primate species. Towards this end, the present study used a polyclonal antibody directed against CNTFR alpha to evaluate the distribution of CNTFR alpha-immunoreactive (-ir) cells within the brain and spinal cord of Cebus apella monkeys. CNTFR alpha-ir was found exclusively within neurons. In the anterior horn of the spinal cord, virtually all motor neurons were darkly immunoreactive for CNTFR alpha. A similar pattern of CNTFR alpha-ir was seen within all cranial motor nuclei with general somatic efferent function (III, IV, motor V, VI, VII, and XII cranial nerves). CNTFR alpha-ir was also seen in other regions involved with motor function including the Purkinje cells of the cerebellum, the substantia nigra pars compacta, red nucleus, dorsal motor nucleus of X cranial nerve, and giant neurons of sensory motor neocortex. A few CNTFR alpha-ir neurons were seen within the globus pallidus with concomitant terminal-like staining within the subthalamic nucleus. Autonomic regions such as the mesencephalic nucleus of the trigeminal nerve and the interomedial lateral cell column of the thoracic spinal cord also contained CNTFR alpha-ir neurons. Finally, the hippocampus displayed dense CNTFR alpha-ir within the pyramidal cell layer of the hippocampal formation and the granule cell layer of the dentate gyrus. The dense expression of this CNTFR alpha protein within regions subserving motor, autonomic, and sensory functions suggests that CNTFR alpha supports many central nervous system regions with diverse functions.