19-06-08(10:33:07)
Authors:
Franziska Marschinke
Per-Arne Oldenborg
Ingrid Strömberg
Institutions:
Integrative medical biology
Histology with cellbiology
Title of abstract : Blocking CD47 affects nerve fiber formation from cultured VM dopamine neurons
Abstract text:
Fetal ventral mesencephalic (VM) cultures have been utilized to find guiding cues for dopamine nerve fiber formation to enhance outgrowth from grafted dopamine neurons in Parkinson´s disease. Dopamine nerve fiber growth in VM cultures occurs in two timely separated sequences. Long-distance outgrowth is found at early time points, without any guidance of glial cells and it disappears at longer time points. A long-term dopamine nerve fiber outgrowth appears at 5 to 7 days in vitro in the presence of glial cells. The integrin associated protein CD47 is expressed in all tissues and serves as a ligand for the signal regulatory protein (SIRP) α, which is e.g. a promoter for migration. VM tissue from CD47 +/+ and CD47-/- mice were used to study astrocytic migration and the outgrowth of the different dopamine nerve fiber populations. The cultures were performed either at days 7 or 14 and stained for tyrosine hydroxylase (TH), an indirect marker for dopamine neurons and an astrocytic marker. TH–immunohistochemistry demonstrated that the non-glial-guided nerve fiber outgrowth in CD47-/- mice reached significantly longer distances from the tissue slice with a massive appearance compared to CD47+/+ mice after 14 DIV. A similar effect appeared when adding CD47 antibodies to the medium of CD47+/+ cultures. Neither at day 7 nor at day 14 the astrocytic migration and the glial-guided dopamine nerve fiber outgrowth in CD47-/- mice displayed a difference compared CD47+/+ mice. It has been observed that the non-glial-guided dopamine nerve fiber outgrowth do not degenerate after 14DIV.
