Sprouting of dopaminergic axons after striatal injury: Confirmation by markers not dependent on dopamine metabolism

Striatal injury increases dopamine metabolism in the nigrostriatal system b ut it is unclear whether this response is due to increased synthesis and ac tivation of tyrosine hydroxylase within existing dopamine terminals and/or branching and sprouting of new terminals. While monitoring the density of t yrosine hydroxylase immunoreactive fibers suggests that sprouting occurs, t his technique alone cannot adequately answer this question since the intens ity of staining and thus the visibility of individual fibers are intimately linked to dopaminergic activity. However, by examining axons and their bra nches using markers that are independent of dopamine metabolism it is possi ble to determine whether dopaminergic sprouting does in fact take place. On e month after using a Scouten wire knife to create a small lesion in the le ft striatum of normal C57/bl-6 mice, silver staining revealed an increase i n the total number of neuronal fibers throughout the injured striatum. This was accompanied by intense staining of tyrosine hydroxylase-positive fiber s around the wound and an increased density of striatal fibers labeled with dextran-biotin after injection of this neuronal tracer into the substantia nigra 1 month after striatal surgery and 5 days prior to sacrifice. The in crease in tyrosine hydroxylase immunoreactivity confirms previous observati ons of increased dopaminergic activity after striatal injury. The increases in silver staining and dextran-biotin transport provide independent eviden ce that this increase in dopaminergic activity occurs because of sprouting of new fibers originating in the substantia nigra, (C) 1999 Academic Press.