Rekha J, Chakravarthy Sridhara, Veena L R, Kalai Vani P, Choudhury Rupam, Halahalli Harsha N, Alladi Phalguni Anand, Dhanushkodi Anandh, Nirmala M, Swamilingiah Geetha M, Agrahari Maulishree, Raju T R, Panicker M M, Kutty Bindu M
Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences (NIMHANS Deemed University), Bangalore, India.
Behav Neurosci. 2009 Dec;123(6):1197-217. doi: 10.1037/a0017655.
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.
我们在之前的研究中已经证明，腹侧海马下托损伤会诱导大鼠海马神经退行性变并导致认知障碍。在本研究中，评估了移植绿色荧光蛋白（GFP）标记的海马细胞系（H3-GFP）细胞对腹侧海马下托损伤大鼠建立功能恢复的疗效。还研究了H3-GFP移植细胞在体内的存活情况及其表达营养因子的能力。成年雄性Wistar大鼠接受腹侧海马下托的选择性损伤，并将H3-GFP细胞移植到海马的海马角1（CA1）区。移植细胞主要定居在齿状回，并表达神经营养因子、脑源性神经营养因子（BDNF）和碱性成纤维细胞生长因子（bFGF）。移植了H3-GFP细胞的腹侧海马下托损伤（VSL）大鼠海马中BDNF的表达增强，并且在八臂放射状迷宫和莫里斯水迷宫任务中表现良好。未进行海马移植的VSL大鼠在任务学习中继续表现出认知障碍。本研究证明了H3-GFP移植介导了VSL大鼠认知功能的恢复。我们的研究支持移植物通过营养支持介导宿主再生和功能恢复的观点，尽管这些机制需要进一步研究。
