NIH-3T3 fibroblast transplants enhance host regeneration and improve spatial learning in ventral subicular lesioned rats

Transplants, besides providing neural replacement, also stimulate host regeneration, which could serve as a powerful means to establish functional recovery in CNS insults. Earlier, we have reported the H3-GFP transplant mediated recovery of cognitive functions in the ventral subicular lesioned rats. In the present study, we demonstrate the efficacy of a non-neural fibroblast transplants in mediating host regeneration and functional recovery in ventral subicular lesioned rats.Adult male Wistar rats were lesioned with ibotenic acid in the ventral subiculum (VSL) and were transplanted with NIH-3T3 fibroblast cells into CA1 region of the hippocampus. Ventral subicular lesioning impaired the spatial task performances in rats and produced considerable degree of dendritic atrophy of the hippocampal pyramidal neurons. Two months following transplantation, the transplants were seen in the dentate gyrus and expressed BDNF and bFGF. Further, the VSL rats with fibroblast transplants showed enhanced expression of BDNF in the hippocampus and enhanced dendritic branching and increased spine density in the CA1 hippocampal pyramidal neurons. Transplantation of fibroblast cells also helped to establish functional recovery and the rats with transplants showed enhanced spatial learning performances. We attribute the recovery of cognitive functions to the graft mediated host regeneration, although the mechanisms of functional recovery remain to be elucidated.

Research highlights▶ The ventral subicular lesion caused hippocampal neurodegeneration and cognitive impairment. ▶ The lesioned rats with fibroblast transplants showed enhanced hippocampal BDNF expression. ▶ The fibroblast cells express MAP-2 in vivo suggesting its ability to transform into neural lineage. ▶ The transplanted rats showed enhanced dendritic branching and spine density of hippocampal neurons. ▶ The lesioned rats with fibroblast transplants showed complete behavioral recovery.