Neural grafting in a rat model of Huntington's disease: striosomal-like organization of striatal grafts as revealed by acetylcholinesterase histochemistry, immunocytochemistry and receptor autoradiography.
Grafts of fetal striatum were implanted in the form of a cell suspension into the brains of rats with prior ibotenic acid lesions of the caudate-putamen. The grafts were placed in three different sites: the lesioned caudate-putamen, or the denervated (but otherwise undamaged) globus pallidus and substantia nigra. After 3-6 months survival the grafts were investigated by means of immunohistochemistry and receptor autoradiography in combination with routine histology and acetylcholinesterase histochemistry. The grafts placed within the lesioned caudate-putamen were at least 10-fold larger larger than those placed in the substantia nigra region, with the grafts placed in the globus pallidus being of intermediate size. In all locations the acetylcholinesterase staining had an uneven, patchy distribution, which was most pronounced in the grafts located within the caudate-putamen. These patches did not bear any obvious relationship to variations in density of the neuronal perikarya within the grafted tissue. Many of the neuropeptide-immunoreactive neuron types present in the normal striatum, such as those containing substance P, [Met]enkephalin, somatostatin, cholecystokinin and neuropeptide Y were also detected in the grafted striatum along with acetylcholinesterase-positive staining. Acetylcholinesterase-positive, [Met]enkephalin-positive, substance P-positive and tyrosine hydroxylase-positive markers all showed uneven, patchy distributions in the grafts. This was also the case for the distribution of dopamine D2 and opiate receptors (as revealed by [3H]spiroperidol and [3H]diprenorphine autoradiography, respectively), whereas muscarinic receptor binding was even throughout the grafts. As is the case in the so-called striosomal patches (neurochemically defined compartments) in the immature intact striatum during the early postnatal period, patches of high acetylcholinesterase staining in the grafts showed partial correspondence with patches of high [Met]enkephalin fibre staining, and dopamine receptor density, and (although to a lesser degree) also with patches of high opiate receptor density and high substance P-immunoreactivity. This correspondence of patches also occurred between tyrosine hydroxylase fibre staining and acetylcholinesterase staining as revealed by grafts placed into the substantia nigra. These results suggest that the fetal striatal cell suspension grafts will give rise to a fairly normal range of striatal neuron and receptor types and that they develop at least some of the striosomal features characteristic for the normal striatum.(ABSTRACT TRUNCATED AT 400 WORDS)
Isacson
O
O
Department of Histology, University of Lund, Sweden.
Dawbarn
D
D
Brundin
P
P
Gage
F H
FH
Emson
P C
PC
Björklund
A
A
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D003342:Corpus Striatum / Q000196:embryology / Q000637:transplantation*; D006651:Histocytochemistry; D006816:Huntington Disease / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007051:Ibotenic Acid; D007150:Immunohistochemistry; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid; D000110:Acetylcholinesterase