Developmental changes in cerebellar endothelin-1 receptors in the neurologic mouse lurcher mutant.
In order to elucidate the role of neuromodulator endothelin-1 (ET-1) in cerebellar degeneration we determined ET-1 receptor binding in the control and lurcher mice cerebella at different postnatal (P) ages. The lurcher mutant is a suggested animal model for human cerebellar ataxias. The cerebellar membranes were prepared from 5 to 20 day old lurcher mice and littermate controls. ET-1 receptor binding was determined using radioligand assay and affinity cross-linking. There was a significant decrease in [125I]ET-1 receptor binding with increasing postnatal age in the control and lurcher mice cerebella. Lurcher mice showed a significant increase in [125I]ET-1 receptor binding at P 9 to P 20 as compared with the controls. Whereas, at P5 to P7 no significant change was observed. By autoradiography, ET-1 receptors were localized in tile granule cell layer of 15 day old control and lurcher mice cerebella. Whereas, the lUrcher mice showed an increase in [125I]ET-1 binding in the cerebellum as compared with the littermate controls. The results of the present study suggest that the increase in ET-1 receptor binding as early as P9 (when neuronal loss is minimal) in the lurcher mutant may reflect upregulation of ET-1 receptors in the degenerating neurons. At P 15 to P 20, when about 50% to 75% neurons are lost respectively, these changes may also reflect astrogliosis.
Vig
P J
PJ
Department of Neurology, University of Mississippi Medical Center, Jackson 39216, USA.
Desaiah
D
D
Subramony
S H
SH
Fratkin
J D
JD
D000367:Age Factors; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D002531:Cerebellum / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D017466:Receptors, Endothelin / Q000187:drug effects* / Q000502:physiology*
D016232:Endothelins; D017466:Receptors, Endothelin