Cj. Leblanc et al., Morris water maze analysis of 192-IgG-saporin-lesioned rats and porcine cholinergic transplants to the hippocampus, CELL TRANSP, 8(1), 1999, pp. 131-142
Adults rats were lesioned with 192-IgG-saporin, an immunotoxin that targets
cholinergic neurons in the basal forebrain expressing the low-affinity ner
ve growth factor receptor (p75). One month later, rats received E30-35 porc
ine cholinergic neurons bilaterally into the hippocampus, and were tested i
n the Morris water maze and the passive avoidance task 4.56 months after tr
ansplantation (in two experiments, rats were retested in the water maze) fo
llowed by histological and cellular analyses. The 192-IgG-saporin-lesioned
animals displayed clear cognitive deficits in the Morris water maze. In all
experiments the lesioned animals had spatial probe deficits on day 5 testi
ng. A large variance was found among the transplanted animals, with individ
ual animals exhibiting improved performance, but little overall improvement
when compared to lesion-alone animals as a group. The relationships betwee
n behavioral performance and graft cholinergic factors were established by
histological analyses. Grafted animals exhibited an increase in cholinergic
innervation of the dentate gyrus (DG) region of the dorsal hippocampus whe
n compared to lesion-alone animals. There was a significant correlation bet
ween the level of cholinergic innervation in the dentate gyrus and spatial
navigation performance (latency and spatial probe) in the Morris water maze
task. These data provide evidence of memory and spatial deficits following
cholinergic denervation, and of target-specific growth of xenogeneic choli
nergic neurons into the hippocampus. The lack of a clear treatment (transpl
ant) effect in the behavioral measures leads us to believe that functional
restoration of cognitive function would require cholinergic reinnervation o
f both the hippocampus and the neocortex in this 192-IgG-saporin animal mod
el.