Long-term, dynamic synaptic reorganization after GABAergic precursor cell transplantation into adult mouse spinal cord.
Long-term, dynamic synaptic reorganization after GABAergic precursor cell transplantation into adult mouse spinal cord.
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DOI：
10.1002/cne.24346
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发表时间：
2018-02-15
期刊：
影响因子：
--
通讯作者：
Bráz JM
中科院分区：
文献类型：
--
作者：
Llewellyn-Smith IJ;Basbaum AI;Bráz JM
将内侧神经节隆起 (MGE) 的 GABA 能神经元胚胎前体移植到成年小鼠脊髓中，可改善神经性疼痛周围神经损伤模型中的机械和热超敏反应。尽管 Fos 和跨神经元示踪研究强烈表明，MGE 衍生的神经元整合到宿主脊髓回路中是功能恢复的基础，但移植细胞突触整合的程度尚未确定。在这里，我们使用电子显微镜免疫细胞化学来评估短期（5-6 周）或长期（4-6 个月）移植的完整成年小鼠中表达 GFP 的 MGE 衍生神经元前体直接整合到背角电路中。我们通过预嵌入亲和素-生物素过氧化物酶检测 GFP，通过嵌入后免疫金标记检测 GABA。在移植后的短期和长期，我们在 GFP 免疫反应性 MGE 细胞体和树突上发现了宿主衍生的突触。 6 个月时，具有突触输入的树突比例从 50% 增加到 80%。在所有小鼠中，MGE 衍生的末端与 GFP 阴性（宿主）细胞体和树突形成突触，并且出乎意料地与一些 GFP 阳性（即 MGE 衍生）树突形成突触，可能反映了移植神经元之间的自突或串扰。我们还观察到 MGE 和主机终端之间的轴轴并置。 GABA 免疫金标记证实移植细胞具有 GABA 能，并且一些移植细胞接受了抑制性 GABA 能输入。我们得出的结论是，移植的 MGE 神经元保留了其 GABA 能表型，并动态整合到宿主-移植突触回路中。结合我们之前的电生理学分析，我们得出结论，MGE 细胞不是 GABA 泵，而是通过突触释放 GABA 来减轻疼痛和瘙痒。
Transplanting embryonic precursors of GABAergic neurons from the medial ganglionic eminence (MGE) into adult mouse spinal cord ameliorates mechanical and thermal hypersensitivity in peripheral nerve injury models of neuropathic pain. Although Fos and transneuronal tracing studies strongly suggest that integration of MGE-derived neurons into host spinal cord circuits underlies recovery of function, the extent to which there is synaptic integration of the transplanted cells has not been established. Here, we used electron microscopic immunocytochemistry to assess directly integration of GFP-expressing MGE-derived neuronal precursors into dorsal horn circuitry in intact, adult mice with short- (5–6 weeks) or long-term (4–6 months) transplants. We detected GFP with pre-embedding avidin-biotin-peroxidase and GABA with post-embedding immunogold labeling. At short and long times post-transplant, we found host-derived synapses on GFP-immunoreactive MGE cells bodies and dendrites. The proportion of dendrites with synaptic input increased from 50% to 80% by 6 months. In all mice, MGE-derived terminals formed synapses with GFP-negative (host) cell bodies and dendrites and, unexpectedly, with some GFP-positive (i.e., MGE-derived) dendrites, possibly reflecting autoapses or cross talk among transplanted neurons. We also observed axoaxonic appositions between MGE and host terminals. Immunogold labeling for GABA confirmed that the transplanted cells were GABAergic and that some transplanted cells received an inhibitory GABAergic input. We conclude that transplanted MGE neurons retain their GABAergic phenotype and integrate dynamically into host-transplant synaptic circuits. Taken together with our previous electrophysiological analyses, we conclude that MGE cells are not GABA pumps, but alleviate pain and itch through synaptic release of GABA.
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影响因子：
3.3
作者：
Llewellyn-Smith, I. J.;Reimann, F.;Gribble, F. M.;Trapp, S.
通讯作者：
Trapp, S.
影响因子：
5.3
作者：
Etlin, Alex;Braz, Joao M.;Basbaum, Allan I.
通讯作者：
Basbaum, Allan I.
DOI：
10.1073/pnas.0900141106
发表时间：
2009-09-08
影响因子：
11.1
作者：
Baraban, Scott C.;Southwell, Derek G.;Alvarez-Buylla, Arturo
通讯作者：
Alvarez-Buylla, Arturo
DOI：
10.3109/07367228609144599
发表时间：
1986-01-01
期刊：
SOMATOSENSORY RESEARCH
影响因子：
--
作者：
BASBAUM, AI;GLAZER, EJ;OERTEL, W
通讯作者：
OERTEL, W
影响因子：
7.2
作者：
Silver, Jerry;Schwab, Martin E.;Popovich, Phillip G.
通讯作者：
Popovich, Phillip G.