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.

Thy-1 immunoreactivity distinguishes patches/striosomes from matrix in the early postnatal striatum of the rat.

At P0, P2 and P3, islands of increased density of Thy-1-immunoreactive (Thy-1-IR) material, which coincided with the islands of dense dopaminergic axons, were noted in the striatum. By P5, the distribution of Thy-1-IR material was homogeneous throughout the developing striatum, but islands of dense dopaminergic axons persisted. The pattern of appearance of Thy-1, which is involved in extension of neurites and stabilization of synapses, suggests that it is involved in formation of connections between the substantia nigra and striatum in the developing rat brain.

Mesostriatal dopaminergic axons transiently express high levels of NILE during development.

The distribution of nerve growth factor-inducible large external (NILE) glycoprotein in the developing mesostriatal dopaminergic system was studied by immunolabeling prenatal, postnatal, and adult rat brains for both NILE and tyrosine hydroxylase (TH). NILE-immunoreactive (NILE-IR) material outlined the TH-immunoreactive (TH-IR) neurons in the ventral mesencephalon at ages E14, E15, and E16 but not at later ages. Fascicles of TH-IR axons in the developing mesostriatal dopaminergic tract were strongly immunoreactive for NILE from E15 through E20. In the postnatal brain, NILE-IR material no longer clearly outlined the fascicles of dopaminergic axons as they ran from the mesencephalon to the striatum. In the striatum of postnatal and adult rats, NILE-IR material was diffusely distributed through the neuropil. Our observations suggest that NILE may play a role in guidance of growing dopaminergic axons in the developing mesostriatal tract and aggregation of the dopaminergic axons into fascicles.

Mesencephalic dopaminergic cells exhibit increased density of neural cell adhesion molecule and polysialic acid during development.

In the developing mesencephalon of the rat, the dopaminergic neurons are generated in the ventricular zone of the basal plate between E11 and E15 and then migrate along radial glia to the ventral surface of the developing mesencephalon. To study the factors that control migration and maturation of the dopaminergic neurons, we immunolabeled embryo and pups, ages E12-P21, for neural cell adhesion molecule (NCAM), polysialic acid (PSA) - a polysaccharide found in high amounts on NCAM during development, tyrosine hydroxylase (TH) - a marker of mesencephalic dopaminergic cells, and vimentin - the major cytoskeletal protein in radial glia in the rat. At E13, we noted that cells throughout the mesencephalon contained NCAM-immunoreactive (NCAM-IR) material but that cells along the ventral surface of the mesencephalon contained an increased amount of NCAM-IR material and PSA-immunoreactive (PSA-IR) material. At this age, we first noted a small number of TH-immunoreactive (TH-IR) cells adjacent to the marginal zone of the ventral surface of the mesencephalon. Many of the TH-IR cells contained an increased density of NCAM-IR material. At age E14, the pattern of increased density of NCAM-IR material on cells along the ventral surface of the mesencephalon persisted and a conspicuous amount of PSA-IR material was also noted on cells in this region. TH-IR cells were more numerous, and a striking number of the TH-IR cells also contained an increased amount of NCAM-IR material and PSA-IR material. With increasing age the distribution of NCAM-IR material and PSA-IR material in the mesencephalon became more uniform. Our work suggests that NCAM may be involved in control of migration and synthesis of TH in the dopaminergic cells of the developing mesencephalon.