Basal EGR-1 (zif268, NGFI-A, Krox-24) expression in developing striatal patches: role of dopamine and glutamate.

Egr-1 (also known as zif268, NGFI-A, or Krox 24) is an immediate-early gene of the zinc finger family that exhibits relatively high constitutive expression in the brain, as well as inducibility by seizure activity, stimulants, and salient physiological stimuli. Immunocytochemical detection of the Egr-1 protein in the developing striatum revealed that in the late prenatal and early postnatal period, Egr-1 protein was expressed selectively in patches of striatal neurons under basal conditions. Egr-1 immunoreactivity was co-expressed with known markers of striatal patch neurons, indicating that expression was greatest in the striatal patch compartment. This patchy expression of Egr-1 transitioned to a nearly homogeneous pattern of Egr-1-immunoreactive cells by postnatal day 10, at which time most striatal neurons appeared to be Egr-1-immunoreactive. The dopamine D1 antagonist SCH23390 (0.5-1.0 mg/kg) reduced Egr-1 expression during the first week postnatal, but it was no longer effective at postnatal day 10. On the other hand, the noncompetitive NMDA antagonist MK-801 (0.5-1.0 mg/kg) became more effective at reducing Egr-1 expression with age. Neonatal destruction of nigrostriatal dopamine afferents reduced the basal pattern of Egr-1 expression for 2-3 days after the lesion, but then Egr-1 expression returned. Thus, Egr-1 expression in the developing striatum appears to be driven first by dopaminergic afferents, and then later in development by excitatory glutamatergic afferents.