Astrocytes from cerebral cortex or striatum attract adult host serotoninergic axons into intrastriatal ventral mesencephalic co-grafts

The identification of axon growth inhibitory molecules offers new hopes for repair of the injured CNS. However, the navigational ability of adult CNS axons and the guidance cues they can recognize are still essentially unknow n. Astrocytes may express guidance molecules and are known to have differen t regional phenotypes. To evaluate their influence on the affinity of adult serotoninergic (5-HT) axons for a projection target, we co-implanted astro cytes from the neonatal striatum, cortex, or ventral mesencephalon together with fetal ventral mesencephalic, tissue into the striatum of adult rats. Two months after surgery; quantification after in vitro 5-[1,2-H-3]serotoni n ([H-3]5-HT) uptake and autoradiography showed that ventral mesencephalic grafts with co-grafted cortical or striatal astrocytes were four times and three times, respectively, more densely innervated by host 5-HT axons than control ventral mesencephalic, grafts with or without co-grafted ventral me sencephalic astrocytes. Immunohistochemistry for glial fibrillary acidic pr otein, vimentin, or chondroitin-sulfate proteoglycans revealed no qualitati ve or quantitative differences in host astroglial scar or production of inh ibitory molecules that could explain these differences in 5-HT innervation. These results demonstrate that astrocytes grown in culture from different brain regions have the potential to influence the growth and maintenance of adult 5-HT axons in a graft of neural tissue from another brain region. It should now be feasible to identify the molecules expressed by cultured cor tical or striatal, but not by ventral mesencephalic, astrocytes that have t hese tropic actions on 5-HT axons of the neostriatum.