Expression of GAP43 mRNA in normally developing and transplanted neurons from the rat ventral mesencephalon.

Abstract

These experiments were designed to determine whether the neuronal growth-related protein GAP43 is expressed at high levels by neurons that collateralize extensively or have long periods of synaptogenesis. We also evaluated the effects of target availability on GAP43 expression. Dopaminergic neurons of the rat ventral mesencephalon (VM) were chosen for investigation because they undergo extensive collateralization and synaptogenesis during postnatal development. Double label in situ hybridization histochemistry (ISHH) and immunocytochemistry (ICC) were used to measure changes in GAP43 mRNA levels within tyrosine hydroxylase (TH)-immunoreactive and -nonimmunoreactive neurons of the VM during postnatal development (p5-adult). TH neurons show higher levels of GAP43 mRNA than do non-TH neurons throughout normal postnatal development and in the adult. This result may be due to more extensive axonal arborization and synaptic remodeling on the part of TH neurons as they innervate the striatum. To test the effects of target availability on GAP43 utilization, grafts of embryonic (e15) VM were placed within previously 6-hydroxydopamine (6-OHDA)-lesioned striata and allowed to develop for 10-28 days. Levels of GAP43 mRNA in grafted TH neurons were reduced at all time points. The short distance to target in the graft paradigm may shorten the overall axonal process length, resulting in lower requirements for growth-related proteins such as GAP43. However, grafted non-TH neurons had elevated levels of GAP43 mRNA, perhaps attributable to prolonged target seeking by neurons that have been isolated from their normal targets.