The effects of donor stage on the survival and function of embryonic striatal grafts in the adult rat brain. II. Correlation between positron emission tomography and reaching behaviour.
Grafts of embryonic striatal primordia are able to elicit behavioural recovery in rats which have received an excitotoxic lesion to the striatum, and it is believed that the P zones or striatal-like tissue within the transplants play a crucial role in these functional effects. We performed this study to compare the effects of different donor stage of embryonic tissue on both the morphology (see accompanying paper) and function of striatal transplants. Both the medial and lateral ganglionic eminence was dissected from rat embryos of either 10 mm, 15 mm, 19 mm, or 23 mm crown-rump length, and implanted as a cell suspension into adult rats which had received an ibotenic acid lesion 10 days prior to transplantation. After four months the animals were tested on the "staircase task" of skilled forelimb use. At 10-14 months rats from the groups which had received grafts from 10 mm or 15 mm donor embryos were taken for positron emission tomography scanning in a small diameter positron emission tomography scanner, using ligands to the dopamine D1 and D2 receptors, [11C]SCH 23390 and [11C]raclopride, respectively. A lesion-alone group was also scanned with the same ligands for comparison. Animals which had received transplants from the 10 mm donors showed a significant recovery with their contralateral paw on the "staircase test". No other groups showed recovery on this task. Similarly, the animals with grafts from the youngest donors showed a significant increase in D1 and D2 receptor binding when compared to the lesion-alone group. No increase in signal was observed with either ligand in the group which had received grafts from 15 mm donors. Success in paw reaching showed a strong correlation to both the positron emission tomography signal obtained and the P zone volume of the grafts. These results suggest that striatal grafts from younger donors (10 mm CRL) give greater behavioural recovery than grafts prepared from older embryos. This recovery is due to both the increased proportion of striatal-like tissue within the grafts and an increase in functional D1 and D2 dopamine receptors measured by positron emission tomography, i.e. a more extensive integration of the graft with the host brain.
Fricker
R A
RA
Department of Experimental Psychology and MRC Cambridge Centre for Brain Repair, University of Cambridge, U.K.
Torres
E M
EM
Hume
S P
SP
Myers
R
R
Opacka-Juffrey
J
J
Ashworth
S
S
Brooks
D J
DJ
Dunnett
S B
SB
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000000981:diagnostic imaging*; D016380:Brain Tissue Transplantation; D002470:Cell Survival / Q000502:physiology*; D003342:Corpus Striatum / Q000637:transplantation*; D004624:Embryo Transfer; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014055:Tomography, Emission-Computed