NEUROTROPHINS AND THEIR TRK RECEPTORS IN CULTURED-CELLS OF THE GLIAL LINEAGE AND IN WHITE-MATTER OF THE CENTRAL-NERVOUS-SYSTEM

Previous studies have analyzed the expression of different members of the neurotrophin family and their trk receptors in glial cultures comp osed mainly or exclusively of type-1 astrocytes, whereas only partial data have been published on other cultured glial types. In this articl e we compare the mRNA levels for neurotrophins (NGF, BDNF, NT-3, NT-4) and their high-affinity receptors (trkA, trkB, trkC) in cultures enri ched in specific glial types, such as microglia, type-1 astroglia, and cells of the O/2A lineage (type-2 astroglia and oligodendroglia). Rel atively high levels of NGF mRNA (comparable to those observed in adult rat cerebral cortex) are present in all types of cultured glial cells , except for a low level of expression in cultures enriched in microgl ial cells. in contrast, BDNF mRNA is undetectable in all cultures exam ined. NT-3 and NT-4 mRNA molecules, at a level equal to that observed in adult rat cerebral cortex, are easily detected in type-1 astrocyte cultures, whereas their hybridization signals are undetectable in cell s of the O/2A lineage and in microglial cultures. The analysis of neur otrophin receptor mRNAs confirms the absence of trkA mRNA, the presenc e of relatively high levels of trkB mRNA (70-100% of cerebral cortex v alues), and low levels of trkC mRNA (10-18% of cerebral cortex values) in both cultured astroglial and oligodendroglial cells. Only very low levels of trkB and trkC mRNAs are observed in microglial cultures. Al though cultured glial cells express mainly mRNAs encoding for the trun cated form of trkB and trkC, a low level of mRNA encoding for the full -length catalytic form of these receptors is detected by the sensitive ribonuclease protection assay. However, NT-3 and NT-4 increase zif/26 8 expression in oligodendroglial cultures, but not in type-1 astroglia l cultures. The presence of these transcripts has been also examined i n white matter regions that are devoid of neuronal cell bodies and enr iched in glial cells (optic nerve and the corpus callosum). Both corpu s callosum and optic nerve show the presence of NGF, NT-3, and NT-4 mR NA, whereas BDNF mRNA level is very low or undetectable; trkA mRNA is absent, although both the truncated and full-length trkB and trkC mRNA are detected. In conclusion, in vivo (central nervous system white ma tter) and in vitro (glial cultures) results support the hypothesis tha t cells of the glial lineage can be both a source of neurotrophins and a cellular target for their actions.