Calretinin-containing axons and neurons are resistant to an intrastriatal 6-hydroxydopamine lesion

Relative preservation of dopaminergic axons in patches and a subcallosal layer was observed in the dorsal, lateral and caudal striatum 4 weeks after intrastriatal injection of 6-hydroxydopamine (6-OHDA), a neurotoxin selective for catecholaminergic neurons. Since calcium binding proteins are reported to provide neuroprotective influence in neurons, differences in the distribution of the calcium binding proteins might be related to the different vulnerabilities of dopaminergic neurons and axons to neurotoxins. To address this possibility, we characterized patches of relatively dense tyrosine hydroxylase-immunoreactive (TH-IR) axons in intrastriatal 6-OHDA lesioned rats, focusing on two calcium binding proteins, calbindin (CB) and calretinin (CR). The patches and subcallosal layer of preserved dopaminergic axons in the striatum of rats lesioned with 6-OHDA contained CR, a 31-kDa calcium-binding protein, but interestingly not CB. Dopaminergic neurons containing CR in the substantia nigra pars compacta (SNpc) were relatively spared compared to those that did not contain CR. Taken together, our data indicate that dopaminergic axons and neurons containing CR in the nigrostriatal pathway are more resistant to 6-OHDA lesion than those that do not contain CR.