Background: Oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes are both lost in central nervous system injury and disease. Activated microglia may play a role in OPC and oligodendrocyte loss or replacement, but it is not clear how the responses of OPCs and oligodendrocytes to activated microglia differ.
Regulation and maintenance of cerebrospinal fluid (CSF) composition is crucial for brain function. Choroid plexus epithelial cells (CPECs) secrete most of the CSF and regulate its ion and water composition. However, the mechanisms of secretion and absorption of water across choroid plexus epithelium (CPE) are poorly understood. Secretion of CSF entails net water movement across CPECs from the basolateral membrane (blood‐facing) through the apical membrane (CSF‐facing). Water fluxes across cell membranes occur through aquaporin channels and cotransporters like the Na+‐K+‐2Cl‐ cotransporter 1 (NKCC1). Both NKCC1 and aquaporin‐1 (AQP1) are expressed in the CPECs apical membrane but are undetectable in the basolateral membrane. The inward water flux across the basolateral membrane of CPECs may be explained by the expression of other members of the gene families of AQPs and/or the cation‐coupled chloride cotransporters (slc12a). Using RT‐PCR, we detected transcripts for several AQPs in whole choroid plexus tissue. Transcripts for AQPs 1, 4, 7, but not 9, have so far been found. Immunolabeling studies in process will reveal the location of these proteins in the various components of the choroid plexus. Explaining the mechanisms of CSF production and absorption is key for understanding pathologies like hydrocephalous and increased intracranial pressure that cause brain ischemia and/or edema. Grant Funding Source: Supported by 226119 Seed Grant Proteomics Program 2012 Boonshoft School of Medicine
Choroid plexus epithelial cells (CPECs) secrete cerebrospinal fluid (CSF) and regulate its electrolyte composition. CPECs express Na+/K+ ATPase and Na+‐K+‐2Cl− cotransporter 1 (NKCC1) on their apical membrane (CSF‐facing), deviating from typical basolateral membrane location in secretory epithelia. Given this non‐canonical location of NKCC1 for a secretory epithelial cell, the direction of net ion fluxes mediated by this cotransporter and associated water fluxes, under physiological conditions, is controversial in CPECs. NKCC1‐mediated ion and water fluxes are tightly linked, thus their direction can be inferred by measuring cell volume changes following NKCC1 inactivation. Hypotheses: under physiological conditions NKCC1 is working in the uptake mode and maintains normal cell water volume in CPECs, hence knocking out NKCC1 will produce cell shrinkage due to unbalanced net efflux of solutes and water. Electron microscopy revealed NKCC1−/− CPECs are severely shrunken, forming large dilations of their basolateral extracellular spaces, yet remain attached by apical tight junctions. Nomarski microscopy confirmed that freshly dissociated CPECs from NKCC1−/− mice are half the size of CPECs from WT (p< 0.01). These results demonstrate that under physiological conditions NKCC1 is constitutively active, works in the uptake mode, and is necessary to maintain normal cell water volume.
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