Projection neurons in fetal striatal transplants are predominantly derived from the lateral ganglionic eminence

• Published in: Neuroscience Vol. 69; no. 4; pp. 1169 - 1182
• Main Authors: Olsson, M., Campbell, K., Wictorin, K., Björklund, A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-12-1995; Elsevier
• Subjects: Animals; Animals, Newborn; Biological and medical sciences; Brain Tissue Transplantation; Corpus Striatum - transplantation; DARPP-32; Development. Senescence. Regeneration. Transplantation; embryonic tissue graft; Female; Fundamental and applied biological sciences. Psychology; Ibotenic Acid - pharmacology; ibotenic acid lesion; Immunohistochemistry; Mice; Neural Pathways - physiology; Prosencephalon - physiology; Rats; Rats, Sprague-Dawley; Rodentia; striatal development; Vertebrates: nervous system and sense organs; xenograft; AchE; E; striatal development; embryonic tissue graft; DARPP-32; M6; MGE; LGE; DMEM; xenograft; TH; KPBS; NHS; ibotenic acid lesion; Rat; Rodentia; Central nervous system; Huntington disease; Telencephalon; Projection; Basal ganglion; Corpus striatum; Transplantation; Vertebrata; Mammalia; Mouse; Brain (vertebrata)
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/0306-4522(95)00325-D

In the present study, we have characterized aspects of integration, growth and phenotypic differentation of embryonic grafts derived from the selective dissection of either the lateral or medial portion of the ganglionic eminences of the rodent forebrain. Donor tissues were derived from embryonic day 15 rat, or embryonic day 14 mouse embryos, and injected as single cell suspensions into the striatum or substantia nigra of adult rats previously subjected to an intrastriatal ibotenic acid lesion. Two to six weeks following grafting, immunocytochemical detection of DARPP-32, the 32,000 mol. wt dopamine-and cyclic AMP-regulated phosphoprotein, was used to identify areas with a striatum-like phenotype within both the intrastriatal and the intranigral grafts. It was thus revealed that all the lateral ganglionic eminence grafts, irrespective of their replacement, were dominated by striatum-like tissue (up to 90% of the total graft volume), while the medial ganglionic eminence transplants were only sparsely positive (< 10% of the total graft volume). These striatum-like regions of the grafts were selectively innervated by tyrosine hydroxylase immunopositive fibres from the host substantia nigra. Furthermore, axons derived from the lateral ganglionic eminence mouse grafts placed in the striatum, as detected by the mouse-specific neuronal marker M6, showed a more extensive and directed outgrowth towards the globus pallidus when compared to fibres emanating from the medial ganglionic eminence grafts. Mouse lateral and medial ganglionic eminence grafts placed into the substancia nigra exhibited similar fibre outgrowth patterns: both types of grafts thus innervated the substantia nigra-pars reticulata and extended axons into the cerebral peduncle.
These results show the DARPP-32-positive striatal projection neurons are derived, for the most part, from the lateral ganglionic eminence and that the restricted lateral ganglionic eminence dissection provides a more optimal source of striatal tissue for grafting in the rat Huntington model.