Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | Fluids and Barriers of the CNS |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12987-023-00438-z |
| _version_ | 1797801312592592896 |
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| author | Ryann M. Fame Huixin Xu Aja Pragana Maria Lehtinen |
| author_facet | Ryann M. Fame Huixin Xu Aja Pragana Maria Lehtinen |
| author_sort | Ryann M. Fame |
| collection | DOAJ |
| description | Abstract 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 [1]. 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. |
| first_indexed | 2024-03-13T04:48:32Z |
| format | Article |
| id | doaj.art-81fce8e8d6fd44f8a3ebd077309511a9 |
| institution | Directory Open Access Journal |
| issn | 2045-8118 |
| language | English |
| last_indexed | 2024-03-13T04:48:32Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Fluids and Barriers of the CNS |
| spelling | doaj.art-81fce8e8d6fd44f8a3ebd077309511a92023-06-18T11:22:30ZengBMCFluids and Barriers of the CNS2045-81182023-06-0120111010.1186/s12987-023-00438-zAge-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1Ryann M. Fame0Huixin Xu1Aja Pragana2Maria Lehtinen3Department of Pathology, Boston Children’s Hospital, Harvard Medical SchoolDepartment of Pathology, Boston Children’s Hospital, Harvard Medical SchoolDepartment of Pathology, Boston Children’s Hospital, Harvard Medical SchoolDepartment of Pathology, Boston Children’s Hospital, Harvard Medical SchoolAbstract 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 [1]. 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.https://doi.org/10.1186/s12987-023-00438-zChoroid plexusCerebrospinal fluidPotassium clearanceNKCC1Genome editingAAV |
| spellingShingle | Ryann M. Fame Huixin Xu Aja Pragana Maria Lehtinen Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1 Fluids and Barriers of the CNS Choroid plexus Cerebrospinal fluid Potassium clearance NKCC1 Genome editing AAV |
| title | Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1 |
| title_full | Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1 |
| title_fullStr | Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1 |
| title_full_unstemmed | Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1 |
| title_short | Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1 |
| title_sort | age appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus nkcc1 |
| topic | Choroid plexus Cerebrospinal fluid Potassium clearance NKCC1 Genome editing AAV |
| url | https://doi.org/10.1186/s12987-023-00438-z |
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