Endogenous neural precursors influence grafted neural stem cells and contribute to neuroprotection in the parkinsonian rat.
Endogenous neural precursors influence grafted neural stem cells and contribute to neuroprotection in the parkinsonian rat.
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内源性神经前体会影响移植的神经干细胞，并有助于帕金森氏大鼠的神经保护。
DOI：
10.1111/j.1460-9568.2012.08019.x
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发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
Collier TJ
中科院分区：
文献类型：
--
作者：
Madhavan L;Daley BF;Sortwell CE;Collier TJ
Neuroprotective and neurorescue effects after neural stem/precursor cell (NPC) transplantation have been reported, but the mechanisms underlying such phenomena are not well understood. Our recent findings in a rat Parkinson’s disease (PD) model indicate that transplantation of NPCs before a 6-hydroxydopamine (6-OHDA) insult can result in nigrostriatal protection which is associated with endogenous NPC proliferation, migration and neurogenesis. Here, we sought to determine whether the observed endogenous NPC response (1) contributes to transplanted NPC - mediated neuroprotection and/or (2) affects graft phenotype and function. Host Fischer 344 rats were administered the antimitotic agent cytosine-β-D-arabinofuranoside (Ara-C) to eliminate actively proliferating endogenous neural precursors before being transplanted with NPCs and treated with 6-OHDA to induce nigrostriatal degeneration. Behavioral and histological analyses demonstrate that the neuroprotective response observed in NPC transplanted animals which had not received Ara-C was significantly attenuated in animals which did receive pre-transplant Ara-C. Also, while grafts in Ara-C treated animals showed no decrease in cell number, they exhibited significantly reduced expression of the neural stem cell regulators nestin and sonic hedgehog. In addition, inhibition of the endogenous NPC response resulted in an exaggerated host glial reaction. Overall, the study establishes for the first time that endogenous NPCs contribute to transplanted NPC-mediated therapeutic effects by affecting both grafted and mature host cells in unique ways. Thus, both endogenous and transplanted NPCs are important in creating an environment suitable for neural protection and rescue, and harnessing their synergistic interaction may lead to the optimization of cell-based therapies for PD.
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影响因子：
8.3
作者：
Kobayashi, Tohru;Ahlenius, Henrik;Lindvall, Olle
通讯作者：
Lindvall, Olle
影响因子：
5.3
作者：
Han, SSW;Kang, DY;Fischer, I
通讯作者：
Fischer, I
影响因子：
16.2
作者：
HYNES, M;PORTER, JA;ROSENTHAL, A
通讯作者：
ROSENTHAL, A
DOI：
10.1098/rstb.2004.1474
发表时间：
2004-05-29
影响因子：
6.3
作者：
Imitola, J;Park, KI;Snyder, EY
通讯作者：
Snyder, EY
影响因子：
4.8
作者：
Mahmood, A;Lu, D;Chopp, M
通讯作者：
Chopp, M