TARGET-DEPRIVED CNS NEURONS EXPRESS THE NGF GENE WHILE REACTIVE GLIA AROUND THEIR AXONAL TERMINALS CONTAIN LOW AND HIGH-AFFINITY NGF RECEPTORS

Reactive gliosis is part of the response of central nervous system to injury and neurodegeneration. Cellular components of the reactive glio sis have the capability to synthesize neurotrophic factors, and thus a re capable of affecting the fate of neuronal populations in the injure d tissue. In this study, we explored the putative involvement of react ive glia-derived neurotrophins in sustaining the axonal projections of target-deprived neurons. Neuronal targets of the dorsal column nuclei neurons were suppressed through excitotoxic lesion of the ventrobasal complex of the rat thalamus (VB). Despite the development of reactive gliosis, neither up-regulation of NGF, nor BDNF or NT3 mRNA could be detected by solution hybridization in the lesioned site at all times t ested. In contrast, expression of the LNGFR gene increased progressive ly up to 90 days post-lesion. Immunocytochemical studies localized the LNGFR protein in a subset of small cells with ramified processes rese mbling microglia at 7 and 20 days post-lesion. At longer times, double immunolabelling studies revealed that a substantial part of LNGFR-imm unoreactive cells filling the area of neuronal loss were neither micro glial cells nor astrocytes although presence of LNGFR in a subset of m icroglial cells could not be excluded. Previous ultrastructural studie s of the kainate-lesioned VB suggest that these LNGFR-immunoreactive c ells correspond to oligodendrocytes and/or Schwann cells. At 2 months post-lesion, when LNGFR expression was maximal, increased levels of tr kA mRNA were detected in the lesioned site. Immunocytochemical studies revealed the presence of numerous trkA-immunoreactive astrocytes. Trk B mRNA, encoding the full-length high-affinity receptor for BDNF, rema ined undetectable by non-isotopic in situ hybridization. In contrast t o the lack of neurotrophin gene expression by glial components of the lesioned VB, dorsal column nuclei neurons contained NGF mRNA as reveal ed by in situ hybridization studies at 10 days prior to enhanced LNGFR expression in the lesion - and 2 months post-lesion. In addition, the number and the staining intensity of NGF mRNA-positive neurons was in creased in the target-deprived neurons, as compared with the contra-la teral nucleus projecting to intact targets. These results show that gl ial cells present in a reactive gliosis which develops in the kainic a cid-lesioned thalamus, do not synthesize neurotrophins but instead pro duce high levels of both low- and high-affinity NGF receptors, LNGFR b y Schwann cells/oligodendrocytes and possibly a subset of microglial c ells, and trkA by reactive astrocytes. Presence of NGF mRNA in dorsal column nuclei neurons indicates that these neurons may be a source of ligand for these receptors. These results demonstrate that the differe nt components required for NGF involvement in the 'cross-talk' between neurons and reactive gliosis are present in this experimental model: NGF in neurons, NGF receptors in reactive glial cells. They thus raise the possibility that target-deprived neurons and their glial environm ent have the potential to interact through the NGF/NGF receptors syste m.