Doublecortin-like expressing astrocytes of the suprachiasmatic nucleus are implicated in the biosynthesis of vasopressin and influences circadian rhythms.
Doublecortin-like expressing astrocytes of the suprachiasmatic nucleus are implicated in the biosynthesis of vasopressin and influences circadian rhythms.
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作者：
我们最近发现了一种新的可塑性蛋白，双皮质素样蛋白(DCL)，它特异性地表达于小鼠视交叉上核(SCN)的外壳中。DCL与神经再生等神经再生事件有关，这些事件需要微管细胞骨架的结构重新排列，使细胞体和树突能够动态移动。我们用共聚焦显微镜检测了DCL在SCN中的表达，发现DCL在包裹精氨酸加压素(AVP)表达细胞的GABA转运蛋白3(GAT3)阳性星形胶质细胞中表达。为了研究这些DCL阳性星形胶质细胞在昼夜节律中的作用，我们使用了表达多西环素诱导的短发夹(Sh)RNA靶向DCL mRNA的转基因小鼠(DCL基因敲除小鼠)。与产仔鼠野生型(WT)对照组相比，DCL基因敲除小鼠在恒定的黑暗中表现出显著更短的昼夜休息-活动期，并显著更快地适应时差反应。由于DCL阳性的星形胶质细胞与AVP阳性的细胞密切相关，我们通过三维重建和透射电子显微镜分析了DCL基因敲除小鼠及其仔鼠的AVP表达。我们发现，在DCL基因敲除的小鼠中，AVP阳性细胞的数量显著增加，体积和强度都增加了。我们发现ZT8和ZT20致密的核心囊泡神经元的数量发生了变化，这表明与WT小鼠相比，DCL基因敲除小鼠神经肽生物合成的高峰和低谷受到了抑制。综上所述，我们的数据表明星形胶质细胞的可塑性在昼夜节律的调节中起着重要的作用，并指出在背侧SCN中存在一个特定的DCL+星形胶质细胞-AVP+神经元网络，与AVP的生物合成有关。DCL在GAT3+/GFAP星形胶质细胞中表达，GAT3+/GFAP星形胶质细胞与视交叉上核中产生加压素的神经元相关。DCL击倒导致了对时差的更快调整。DCL基因敲除改变了加压素的生物合成。
We have recently identified a novel plasticity protein, doublecortin‐like (DCL), that is specifically expressed in the shell of the mouse suprachiasmatic nucleus (SCN). DCL is implicated in neuroplastic events, such as neurogenesis, that require structural rearrangements of the microtubule cytoskeleton, enabling dynamic movements of cell bodies and dendrites. We have inspected DCL expression in the SCN by confocal microscopy and found that DCL is expressed in GABA transporter‐3 (GAT3)‐positive astrocytes that envelope arginine vasopressin (AVP)‐expressing cells. To investigate the role of these DCL‐positive astrocytes in circadian rhythmicity, we have used transgenic mice expressing doxycycline‐induced short‐hairpin (sh) RNA's targeting DCL mRNA (DCL knockdown mice). Compared with littermate wild type (WT) controls, DCL‐knockdown mice exhibit significant shorter circadian rest‐activity periods in constant darkness and adjusted significantly faster to a jet‐lag protocol. As DCL‐positive astrocytes are closely associated with AVP‐positive cells, we analyzed AVP expression in DCL‐knockdown mice and in their WT littermates by 3D reconstructions and transmission electron microscopy (TEM). We found significantly higher numbers of AVP‐positive cells with increased volume and more intensity in DCL‐knockdown mice. We found alterations in the numbers of dense core vesicle‐containing neurons at ZT8 and ZT20 suggesting that the peak and trough of neuropeptide biosynthesis is dampened in DCL‐knockdown mice compared to WT littermates. Together, our data suggest an important role for the astrocytic plasticity in the regulation of circadian rhythms and point to the existence of a specific DCL+ astrocyte‐AVP+ neuronal network located in the dorsal SCN implicated in AVP biosynthesis. DCL is expressed in GAT3+/GFAP– astrocytes that are associated with vasopressin–producing neurons in the SupraChiasmatic Nucleus. DCL knockdown results in faster adjustments to jet–lags. DCL knockdown changes the biosynthesis of vasopressin.
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影响因子：
16.6
作者：
Barca-Mayo O;Pons-Espinal M;Follert P;Armirotti A;Berdondini L;De Pietri Tonelli D
通讯作者：
De Pietri Tonelli D
影响因子：
2.5
作者：
CASTEL, M;FEINSTEIN, N;HARARI, N
通讯作者：
HARARI, N
DOI：
10.1523/jneurosci.6576-10.2011
发表时间：
2011-06-08
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Burkeen JF;Womac AD;Earnest DJ;Zoran MJ
通讯作者：
Zoran MJ
影响因子：
2.8
作者：
Deng, Xiao-Hua;Bertini, Giuseppe;Bentivoglio, Marina
通讯作者：
Bentivoglio, Marina
影响因子：
16.2
作者：
Koizumi, H;Tanaka, T;Gleeson, JG
通讯作者：
Gleeson, JG