Median eminence myelin continuously turns over in adult mice.
Median eminence myelin continuously turns over in adult mice.
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DOI：
10.1016/j.molmet.2023.101690
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发表时间：
2023-03
影响因子：
8.1
通讯作者：
Blouet, Clemence
中科院分区：
文献类型：
--
作者：
Buller, Sophie;Kohnke, Sara;Hansford, Robert;Shimizu, Takahiro;Richardson, William D.;Blouet, Clemence
少突胶质细胞祖细胞分化受成人正中隆起（ME）的营养信号调节，但对局部髓鞘形成的后果尚不清楚。本研究的目的是表征髓鞘可塑性在ME的成年小鼠在健康或慢性营养挑战，并确定其相关性的能量平衡的调节。我们使用溴脱氧尿苷标记和遗传命运绘图工具评估了健康成年雄性小鼠ME中新的少突胶质细胞（OL）和髓鞘的产生及其稳定性。我们在PLX 5622处理的C57 BL/6 J小鼠和Pdgfra-Cre/ERT 2; R26 R-eYFP;Myrffl/fl小鼠中评估了小胶质细胞对ME髓鞘可塑性的贡献，其中成年少突神经元生成是钝化的。接下来，我们研究了高脂喂养或热量限制如何影响ME OL谱系进展和髓鞘形成。最后，我们的特点是功能相关的成年少突神经元的能量平衡调节。我们发现，髓鞘形成的OL是连续和快速产生的成人ME。特别是，OL数量和髓鞘量保持显着稳定的成人ME。事实上，新的OL和髓鞘生成的ME的高速率被抵消的连续营业额。我们表明，小胶质细胞所需的连续OL和髓鞘生产，和ME髓鞘可塑性调节招聘当地的免疫细胞。最后，我们提供的证据表明，ME髓鞘形成是由身体的精力充沛的状态，并表明，ME OL和髓鞘可塑性的能量平衡和下丘脑瘦素敏感性的调节所需的。这项研究确定了一种新的机制，调节瘦素的敏感性和中央控制的能量平衡，并揭示了以前不受重视的形式的结构可塑性的ME。新的髓鞘少突胶质细胞是连续和快速产生的成人正中隆起。与其他区域不同，髓鞘少突胶质细胞在成人正中隆起翻转。正中隆起髓鞘可塑性调节局部小胶质细胞的募集和小胶质细胞是需要髓鞘可塑性在瘦小鼠。正中隆起髓鞘形成受身体的能量状态调节。成年大脑中少突胶质细胞的发生是调节能量平衡和下丘脑瘦素敏感性所必需的。
Oligodendrocyte progenitor cell differentiation is regulated by nutritional signals in the adult median eminence (ME), but the consequences on local myelination are unknown. The aim of this study was to characterize myelin plasticity in the ME of adult mice in health or in response to chronic nutritional challenge and determine its relevance to the regulation of energy balance. We assessed new oligodendrocyte (OL) and myelin generation and stability in the ME of healthy adult male mice using bromodeoxyuridine labelling and genetic fate mapping tools. We evaluated the contribution of microglia to ME myelin plasticity in PLX5622-treated C57BL/6J mice and in Pdgfra-Cre/ERT2;R26R-eYFP;Myrffl/fl mice, where adult oligodendrogenesis is blunted. Next, we investigated how high-fat feeding or caloric restriction impact ME OL lineage progression and myelination. Finally, we characterized the functional relevance of adult oligodendrogenesis on energy balance regulation. We show that myelinating OLs are continuously and rapidly generated in the adult ME. Paradoxically, OL number and myelin amounts remain remarkably stable in the adult ME. In fact, the high rate of new OL and myelin generation in the ME is offset by continuous turnover of both. We show that microglia are required for continuous OL and myelin production, and that ME myelin plasticity regulates the recruitment of local immune cells. Finally, we provide evidence that ME myelination is regulated by the body’s energetic status and demonstrate that ME OL and myelin plasticity are required for the regulation of energy balance and hypothalamic leptin sensitivity. This study identifies a new mechanism modulating leptin sensitivity and the central control of energy balance and uncovers a previously unappreciated form of structural plasticity in the ME. New myelinating oligodendrocytes are continuously and rapidly produced in the adult median eminence. Unlike what occurs in other regions, myelinating oligodendrocytes turn over in the adult median eminence. Median eminence myelin plasticity regulates local microglia recruitment and microglia are required for myelin plasticity in lean mice. Median eminence myelination is regulated by the body’s energetic status. Oligodendrogenesis in the adult brain is required for the regulation of energy balance and hypothalamic leptin sensitivity.
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影响因子：
25
作者：
Hughes EG;Orthmann-Murphy JL;Langseth AJ;Bergles DE
通讯作者：
Bergles DE
影响因子：
16.2
作者：
Kang, Shin H.;Fukaya, Masahiro;Yang, Jason K.;Rothstein, Jeffrey D.;Bergles, Dwight E.
通讯作者：
Bergles, Dwight E.
影响因子：
8.8
作者：
Kohnke S;Buller S;Nuzzaci D;Ridley K;Lam B;Pivonkova H;Bentsen MA;Alonge KM;Zhao C;Tadross J;Holmqvist S;Shimizu T;Hathaway H;Li H;Macklin W;Schwartz MW;Richardson WD;Yeo GSH;Franklin RJM;Karadottir RT;Rowitch DH;Blouet C
通讯作者：
Blouet C
影响因子：
9.8
作者：
通讯作者：
--
影响因子：
8.8
作者：
Tripathi RB;Jackiewicz M;McKenzie IA;Kougioumtzidou E;Grist M;Richardson WD
通讯作者：
Richardson WD