Long-term potentiation promotes proliferation/survival and neuronal differentiation of neural stem/progenitor cells.
Long-term potentiation promotes proliferation/survival and neuronal differentiation of neural stem/progenitor cells.
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DOI：
10.1371/journal.pone.0076860
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang YT
中科院分区：
文献类型：
--
作者：
Cho T;Ryu JK;Taghibiglou C;Ge Y;Chan AW;Liu L;Lu J;McLarnon JG;Wang YT
神经干细胞（NSC）替代疗法被认为是治疗各种神经退行性疾病的一种有前途的细胞替代疗法。然而，目前NSC存活率和神经发生率低限制了其临床潜力。在这里，我们研究了海马长时程增强（LTP），突触可塑性的最好的表征形式之一，促进神经发生，促进增殖/生存和神经元分化的神经干细胞。我们发现，诱导海马LTP显着促进增殖/存活和神经元分化的内源性神经前体细胞（NPC）和外源性移植的神经干细胞在大鼠海马。通过全身应用受体拮抗剂3-[（R）-2-羧基哌嗪-4-基]-丙基-1-膦酸（CPP），通过药理学阻断N-甲基-D-天冬氨酸谷氨酸受体（NMDAR），防止LTP诱导，消除了这些效应。此外，使用NPC-神经元共培养系统，我们能够证明LTP促进的NPC神经发生至少部分是由LTP增加的神经元释放脑源性神经营养因子（BDNF）及其随后激活NSC上的原肌肽受体激酶B（Trk B）受体介导的。我们的研究结果表明，LTP促进内源性和外源性移植的神经干细胞在脑内的神经发生。该研究表明，在NSC移植之前，用LTP诱导的脑深部刺激方案对宿主脑接收区进行预处理，可能会增加使用NSC移植作为各种神经退行性疾病的有效细胞疗法的成功可能性。
Neural stem cell (NSC) replacement therapy is considered a promising cell replacement therapy for various neurodegenerative diseases. However, the low rate of NSC survival and neurogenesis currently limits its clinical potential. Here, we examined if hippocampal long-term potentiation (LTP), one of the most well characterized forms of synaptic plasticity, promotes neurogenesis by facilitating proliferation/survival and neuronal differentiation of NSCs. We found that the induction of hippocampal LTP significantly facilitates proliferation/survival and neuronal differentiation of both endogenous neural progenitor cells (NPCs) and exogenously transplanted NSCs in the hippocampus in rats. These effects were eliminated by preventing LTP induction by pharmacological blockade of the N-methyl-D-aspartate glutamate receptor (NMDAR) via systemic application of the receptor antagonist, 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP). Moreover, using a NPC-neuron co-culture system, we were able to demonstrate that the LTP-promoted NPC neurogenesis is at least in part mediated by a LTP-increased neuronal release of brain-derived neurotrophic factor (BDNF) and its consequent activation of tropomysosin receptor kinase B (TrkB) receptors on NSCs. Our results indicate that LTP promotes the neurogenesis of both endogenous and exogenously transplanted NSCs in the brain. The study suggests that pre-conditioning of the host brain receiving area with a LTP-inducing deep brain stimulation protocol prior to NSC transplantation may increase the likelihood of success of using NSC transplantation as an effective cell therapy for various neurodegenerative diseases.
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影响因子：
--
作者：
Bronstein JM;Tagliati M;Alterman RL;Lozano AM;Volkmann J;Stefani A;Horak FB;Okun MS;Foote KD;Krack P;Pahwa R;Henderson JM;Hariz MI;Bakay RA;Rezai A;Marks WJ Jr;Moro E;Vitek JL;Weaver FM;Gross RE;DeLong MR
通讯作者：
DeLong MR
DOI：
10.1002/neu.480251107
发表时间：
1994-11-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
BARBACID, M
通讯作者：
BARBACID, M
影响因子：
2.5
作者：
BERNHARDT, R;MATUS, A
通讯作者：
MATUS, A
影响因子：
25
作者：
Denise, A;Garcia, R;Sofroniew, MV
通讯作者：
Sofroniew, MV
影响因子：
2.7
作者：
Chun, Sung Kun;Sun, Woong;Jung, Min Whan
通讯作者：
Jung, Min Whan