Embryonic donor age and dissection influences striatal graft development and functional integration in a rodent model of Huntington's disease.
The method of embryonic dissection and the age of the donor material remain areas of controversy in the preparation of striatal tissue for intrastriatal implantation. This study explores the relationship between these two parameters with respect to the morphology, function, and physiological integration of the resultant grafts. Tissue derived from embryos of 14 and 16 days of gestation (CRL 10-11 and 14-15 mm, respectively) was prepared as whole, lateral, and medial ganglionic eminence suspensions (WGE, LGE, and MGE, respectively). The embryonic material was implanted into the excitotoxically lesioned striatum of host rats. Grafts derived from E14 LGE attenuated drug-induced rotational bias whereas grafts from E14 MGE ameliorated contralateral deficits in paw reaching. Six months after grafting retrograde tracing of graft projections to the globus pallidus was performed followed by electrical excitation of cortical afferent fibers. Grafts derived from E14 WGE had the largest volume of striatum-like tissue and more striatal neurons compared to LGE from the same donor age. These results suggest that MGE tissue as well as LGE plays a role in the structural and functional integration of striatal grafts.
Watts
C
C
MRC Cambridge Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom. cw209@cam.ac.uk
Brasted
P J
PJ
Dunnett
S B
SB
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D016380:Brain Tissue Transplantation / Q000379:methods; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation; D002465:Cell Movement; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000196:embryology / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation*; D003913:Dextroamphetamine / Q000494:pharmacology; D004195:Disease Models, Animal; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D005260:Female; D006085:Graft Survival; D006816:Huntington Disease / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D009419:Nerve Tissue Proteins; D009475:Neurons, Afferent / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism; D011597:Psychomotor Performance; D017378:Quinolinic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D000110:Acetylcholinesterase; D017378:Quinolinic Acid; D003913:Dextroamphetamine