ABSTRACT
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.
Subject(s)
Hippocampus/pathology , Hippocampus/physiopathology , Maze Learning/physiology , NIH 3T3 Cells/transplantation , Regeneration/physiology , Analysis of Variance , Animals , Atrophy , Brain-Derived Neurotrophic Factor/metabolism , Fibroblast Growth Factor 2/metabolism , Hippocampus/metabolism , Ibotenic Acid , Immunohistochemistry , Male , Mice , Neurons/pathology , Neurons/physiology , Rats , Rats, Wistar , Recovery of Function/physiologyABSTRACT
We have demonstrated in our previous studies that ventral subicular lesion induces neurodegeneration of the hippocampus and produces cognitive impairment in rats. In the present study, the efficacy of transplanted green fluorescent protein (GFP)-labeled hippocampal cell line (H3-GFP) cells in establishing functional recovery in ventral subicular lesioned rats has been evaluated. The survival of H3-GFP transplants and their ability to express trophic factors in vivo were also investigated. Adult male Wistar rats were subjected to selective lesioning of ventral subiculum and were transplanted with H3-GFP cells into the cornu ammonis 1 (CA1) hippocampus. The transplants settled mainly in the dentate gyrus and expressed neurotrophic factors, brain-derived neurotrophic factor (BDNF), and basic fibroblast growth factor (bFGF). The ventral subicular lesioned (VSL) rats with H3-GFP transplants showed enhanced expression of BDNF in the hippocampus and performed well in eight-arm radial maze and Morris water maze tasks. The VSL rats without hippocampal transplants continued to show cognitive impairment in task learning. The present study demonstrated the H3-GFP transplants mediated recovery of cognitive functions in VSL rats. Our study supports the notion of graft meditated host regeneration and functional recovery through trophic support, although these mechanisms require further investigation.
