Differential Regulation of Ciliary Neurotrophic Factor (CNTF) and CNTF Receptor α Expression in Astrocytes and Neurons of the Fascia Dentata after Entorhinal Cortex Lesion

Abstract

Neurotrophic factors have been implicated in reactive processes occurring in response to CNS lesions. Ciliary neurotrophic factor (CNTF), in particular, has been shown to ameliorate axotomy-induced degeneration of CNS neurons and to be upregulated at wound sites in the brain. To investigate a potential role of CNTF in lesion-induced degeneration and reorganization, we have analyzed the expression of CNTF protein and CNTF receptor alpha (CNTFR alpha) mRNA in the rat dentate gyrus after unilateral entorhinal cortex lesions (ECLs), using immunocytochemistry and nonradioactive in situ hybridization, respectively. In sham-operated as in normal animals, CNTF protein was not detectable by immunocytochemistry. Starting at 3 d after ECL, upregulation of CNTF expression was observed in the ipsilateral outer molecular layer (OML). Expression was maximal at around day 7, and at this stage immunoreactivity could be specifically localized to astrocytes in the ipsilateral OML. By day 14 postlesion, CNTF immunoreactivity had returned to control levels. CNTFR alpha mRNA was restricted to neurons of the granule cell layer in controls. Three days postlesion, prominent CNTFR alpha expression was observed in the deafferented OML. A similar but less prominent response was noticed in the contralateral OML. After 10 d, CNTFR alpha expression had returned to control levels. Double labeling for CNTFR alpha mRNA and glial fibrillary acidic protein (GFAP) showed that upregulation of CNTFR alpha occurred in reactive, GFAP-immunopositive astrocytes of the OML. A substantial reduction of CNTFR alpha expression in the deafferented granule cells was transiently observed at 7 and 10 d postlesion. Our results suggest a paracrine or autocrine function of CNTF in the regulation of astrocytic and neuronal responses after brain injury.