Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1.
Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1.
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DOI：
10.1186/s12987-023-00438-z
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发表时间：
2023-06-16
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
脑脊液（CSF）的容量和电解质组成的调节对大脑发育和功能至关重要。脉络丛（ChP）中的Na-K-Cl共转运蛋白NKCC 1通过共转运离子和介导同向水运动在调节CSF体积中起关键作用。我们先前的研究表明，ChP NKCC 1在新生小鼠中高度磷酸化，因为CSF K+水平急剧下降，并且ChP中NKCC 1的过表达加速CSF K+清除并减小心室大小。这些数据表明，NKCC 1介导小鼠出生后的CSF K+清除。在本研究中，我们使用CRISPR技术创建了条件性NKCC 1敲除小鼠系，并通过电感耦合等离子体发射光谱（ICP-OES）评估了CSF K+。我们证明了使用AAV 2/5胚胎脑室内递送Cre重组酶后新生小鼠中总NKCC 1和磷酸化NKCC 1的ChP特异性减少。ChP-NKCC 1敲低伴随着CSF K+的延迟围产期清除。在大脑皮层中未观察到大体形态学破坏。我们扩展了我们以前的结果，显示胚胎和围产期大鼠与小鼠共有的关键特征，包括ChP NKCC 1表达水平降低，ChP NKCC 1磷酸化状态增加，以及与成年大鼠相比CSF K+水平增加。总的来说，这些随访数据支持ChP NKCC 1在新生儿发育期间在年龄适当的CSF K+清除中的作用。
Regulation of the volume and electrolyte composition of the cerebrospinal fluid (CSF) is vital for brain development and function. The Na-K-Cl co-transporter NKCC1 in the choroid plexus (ChP) plays key roles in regulating CSF volume by co-transporting ions and mediating same-direction water movements. Our previous study showed ChP NKCC1 is highly phosphorylated in neonatal mice as the CSF K+ level drastically decreases and that overexpression of NKCC1 in the ChP accelerates CSF K+ clearance and reduces ventricle size. These data suggest that NKCC1 mediates CSF K+ clearance following birth in mice. In this current study, we used CRISPR technology to create a conditional NKCC1 knockout mouse line and evaluated CSF K+ by Inductively Coupled Plasma Optical Emission spectroscopy (ICP-OES). We demonstrated ChP-specific reduction of total and phosphorylated NKCC1 in neonatal mice following embryonic intraventricular delivery of Cre recombinase using AAV2/5. ChP-NKCC1 knockdown was accompanied by a delayed perinatal clearance of CSF K+. No gross morphological disruptions were observed in the cerebral cortex. We extended our previous results by showing embryonic and perinatal rats shared key characteristics with mice, including decreased ChP NKCC1 expression level, increased ChP NKCC1 phosphorylation state, and increased CSF K+ levels compared to adult. Collectively, these follow up data support ChP NKCC1’s role in age-appropriate CSF K+ clearance during neonatal development.
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影响因子：
16.2
作者：
Lehtinen MK;Zappaterra MW;Chen X;Yang YJ;Hill AD;Lun M;Maynard T;Gonzalez D;Kim S;Ye P;D'Ercole AJ;Wong ET;LaMantia AS;Walsh CA
通讯作者：
Walsh CA
影响因子：
2.8
作者：
Pace, AJ;Madden, VJ;Henson, MM
通讯作者：
Henson, MM
影响因子：
82.9
作者：
Karimy, Jason K.;Zhang, Jinwei;Kahle, Kristopher T.
通讯作者：
Kahle, Kristopher T.
影响因子：
12.3
作者：
Aida T;Chiyo K;Usami T;Ishikubo H;Imahashi R;Wada Y;Tanaka KF;Sakuma T;Yamamoto T;Tanaka K
通讯作者：
Tanaka K
DOI：
10.1016/s1095-6433(01)00420-2
发表时间：
2001-10-01
影响因子：
2.3
作者：
Isenring, P;Forbush, B
通讯作者：
Forbush, B