Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development
Cerebrospinal fluid (CSF) provides vital support for the brain. Abnormal CSF accumulation, such as hydrocephalus, can negatively affect perinatal neurodevelopment. The mechanisms regulating CSF clearance during the postnatal critical period are unclear. Here, we show that CSF K+, accompanied by wate...
| Main Authors: | , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2021
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| Online Access: | https://hdl.handle.net/1721.1/130390 |
| _version_ | 1826217202073731072 |
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| author | Xu, Huixin Fame, Ryann M. Sutin, Jason Naranjo, Christopher Syau, Della Cui, Jin Shipley, Frederick B. Vernon, Amanda Gao, Fan Yong, Zhang Holtzman, Michael J. Heiman, Myriam Warf, Benjamin C. Lin, Pei-Yi Lehtinen, Maria K. |
| author2 | Picower Institute for Learning and Memory |
| author_facet | Picower Institute for Learning and Memory Xu, Huixin Fame, Ryann M. Sutin, Jason Naranjo, Christopher Syau, Della Cui, Jin Shipley, Frederick B. Vernon, Amanda Gao, Fan Yong, Zhang Holtzman, Michael J. Heiman, Myriam Warf, Benjamin C. Lin, Pei-Yi Lehtinen, Maria K. |
| author_sort | Xu, Huixin |
| collection | MIT |
| description | Cerebrospinal fluid (CSF) provides vital support for the brain. Abnormal CSF accumulation, such as hydrocephalus, can negatively affect perinatal neurodevelopment. The mechanisms regulating CSF clearance during the postnatal critical period are unclear. Here, we show that CSF K+, accompanied by water, is cleared through the choroid plexus (ChP) during mouse early postnatal development. We report that, at this developmental stage, the ChP showed increased ATP production and increased expression of ATP-dependent K+ transporters, particularly the Na+, K+, Cl−, and water cotransporter NKCC1. Overexpression of NKCC1 in the ChP resulted in increased CSF K+ clearance, increased cerebral compliance, and reduced circulating CSF in the brain without changes in intracranial pressure in mice. Moreover, ChP-specific NKCC1 overexpression in an obstructive hydrocephalus mouse model resulted in reduced ventriculomegaly. Collectively, our results implicate NKCC1 in regulating CSF K+ clearance through the ChP in the critical period during postnatal neurodevelopment in mice. |
| first_indexed | 2024-09-23T16:59:39Z |
| format | Article |
| id | mit-1721.1/130390 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:59:39Z |
| publishDate | 2021 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1303902022-10-03T09:40:46Z Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development Xu, Huixin Fame, Ryann M. Sutin, Jason Naranjo, Christopher Syau, Della Cui, Jin Shipley, Frederick B. Vernon, Amanda Gao, Fan Yong, Zhang Holtzman, Michael J. Heiman, Myriam Warf, Benjamin C. Lin, Pei-Yi Lehtinen, Maria K. Picower Institute for Learning and Memory Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Broad Institute of MIT and Harvard Cerebrospinal fluid (CSF) provides vital support for the brain. Abnormal CSF accumulation, such as hydrocephalus, can negatively affect perinatal neurodevelopment. The mechanisms regulating CSF clearance during the postnatal critical period are unclear. Here, we show that CSF K+, accompanied by water, is cleared through the choroid plexus (ChP) during mouse early postnatal development. We report that, at this developmental stage, the ChP showed increased ATP production and increased expression of ATP-dependent K+ transporters, particularly the Na+, K+, Cl−, and water cotransporter NKCC1. Overexpression of NKCC1 in the ChP resulted in increased CSF K+ clearance, increased cerebral compliance, and reduced circulating CSF in the brain without changes in intracranial pressure in mice. Moreover, ChP-specific NKCC1 overexpression in an obstructive hydrocephalus mouse model resulted in reduced ventriculomegaly. Collectively, our results implicate NKCC1 in regulating CSF K+ clearance through the ChP in the critical period during postnatal neurodevelopment in mice. NIH (Grants R01-AI130591 and R35-HL145242) 2021-04-06T15:35:42Z 2021-04-06T15:35:42Z 2021-01 2020-06 2021-03-18T14:28:21Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 https://hdl.handle.net/1721.1/130390 Xu, Huixin et al. "Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development." Nature Communications 12, 1 (January 2021): 447 © 2021 The Author(s). en http://dx.doi.org/10.1038/s41467-020-20666-3 Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Xu, Huixin Fame, Ryann M. Sutin, Jason Naranjo, Christopher Syau, Della Cui, Jin Shipley, Frederick B. Vernon, Amanda Gao, Fan Yong, Zhang Holtzman, Michael J. Heiman, Myriam Warf, Benjamin C. Lin, Pei-Yi Lehtinen, Maria K. Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development |
| title | Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development |
| title_full | Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development |
| title_fullStr | Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development |
| title_full_unstemmed | Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development |
| title_short | Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development |
| title_sort | choroid plexus nkcc1 mediates cerebrospinal fluid clearance during mouse early postnatal development |
| url | https://hdl.handle.net/1721.1/130390 |
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