Transcriptional profiling of transport mechanisms and regulatory pathways in rat choroid plexus
Abstract Background Dysregulation of brain fluid homeostasis associates with brain pathologies in which fluid accumulation leads to elevated intracranial pressure. Surgical intervention remains standard care, since specific and efficient pharmacological treatment options are limited for pathologies...
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | Fluids and Barriers of the CNS |
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| Online Access: | https://doi.org/10.1186/s12987-022-00335-x |
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| author | Søren N. Andreassen Trine L. Toft-Bertelsen Jonathan H. Wardman René Villadsen Nanna MacAulay |
| author_facet | Søren N. Andreassen Trine L. Toft-Bertelsen Jonathan H. Wardman René Villadsen Nanna MacAulay |
| author_sort | Søren N. Andreassen |
| collection | DOAJ |
| description | Abstract Background Dysregulation of brain fluid homeostasis associates with brain pathologies in which fluid accumulation leads to elevated intracranial pressure. Surgical intervention remains standard care, since specific and efficient pharmacological treatment options are limited for pathologies with disturbed brain fluid homeostasis. Such lack of therapeutic targets originates, in part, from the incomplete map of the molecular mechanisms underlying cerebrospinal fluid (CSF) secretion by the choroid plexus. Methods The transcriptomic profile of rat choroid plexus was generated by RNA Sequencing (RNAseq) of whole tissue and epithelial cells captured by fluorescence-activated cell sorting (FACS), and compared to proximal tubules. The bioinformatic analysis comprised mapping to reference genome followed by filtering for type, location, and association with alias and protein function. The transporters and associated regulatory modules were arranged in discovery tables according to their transcriptional abundance and tied together in association network analysis. Results The transcriptomic profile of choroid plexus displays high similarity between sex and species (human, rat, and mouse) and lesser similarity to another high-capacity fluid-transporting epithelium, the proximal tubules. The discovery tables provide lists of transport mechanisms that could participate in CSF secretion and suggest regulatory candidates. Conclusions With quantification of the transport protein transcript abundance in choroid plexus and their potentially linked regulatory modules, we envision a molecular tool to devise rational hypotheses regarding future delineation of choroidal transport proteins involved in CSF secretion and their regulation. Our vision is to obtain future pharmaceutical targets towards modulation of CSF production in pathologies involving disturbed brain water dynamics. |
| first_indexed | 2024-04-12T14:08:57Z |
| format | Article |
| id | doaj.art-bd285311875a4ea494337c18641dbe6f |
| institution | Directory Open Access Journal |
| issn | 2045-8118 |
| language | English |
| last_indexed | 2024-04-12T14:08:57Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Fluids and Barriers of the CNS |
| spelling | doaj.art-bd285311875a4ea494337c18641dbe6f2022-12-22T03:29:59ZengBMCFluids and Barriers of the CNS2045-81182022-06-0119111910.1186/s12987-022-00335-xTranscriptional profiling of transport mechanisms and regulatory pathways in rat choroid plexusSøren N. Andreassen0Trine L. Toft-Bertelsen1Jonathan H. Wardman2René Villadsen3Nanna MacAulay4Department of Neuroscience, Faculty of Health and Medical Sciences, University of CopenhagenDepartment of Neuroscience, Faculty of Health and Medical Sciences, University of CopenhagenDepartment of Neuroscience, Faculty of Health and Medical Sciences, University of CopenhagenDepartment of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of CopenhagenDepartment of Neuroscience, Faculty of Health and Medical Sciences, University of CopenhagenAbstract Background Dysregulation of brain fluid homeostasis associates with brain pathologies in which fluid accumulation leads to elevated intracranial pressure. Surgical intervention remains standard care, since specific and efficient pharmacological treatment options are limited for pathologies with disturbed brain fluid homeostasis. Such lack of therapeutic targets originates, in part, from the incomplete map of the molecular mechanisms underlying cerebrospinal fluid (CSF) secretion by the choroid plexus. Methods The transcriptomic profile of rat choroid plexus was generated by RNA Sequencing (RNAseq) of whole tissue and epithelial cells captured by fluorescence-activated cell sorting (FACS), and compared to proximal tubules. The bioinformatic analysis comprised mapping to reference genome followed by filtering for type, location, and association with alias and protein function. The transporters and associated regulatory modules were arranged in discovery tables according to their transcriptional abundance and tied together in association network analysis. Results The transcriptomic profile of choroid plexus displays high similarity between sex and species (human, rat, and mouse) and lesser similarity to another high-capacity fluid-transporting epithelium, the proximal tubules. The discovery tables provide lists of transport mechanisms that could participate in CSF secretion and suggest regulatory candidates. Conclusions With quantification of the transport protein transcript abundance in choroid plexus and their potentially linked regulatory modules, we envision a molecular tool to devise rational hypotheses regarding future delineation of choroidal transport proteins involved in CSF secretion and their regulation. Our vision is to obtain future pharmaceutical targets towards modulation of CSF production in pathologies involving disturbed brain water dynamics.https://doi.org/10.1186/s12987-022-00335-xCerebrospinal fluidMembrane transportCSF secretionRNA sequencingRNAseqBioinformatics |
| spellingShingle | Søren N. Andreassen Trine L. Toft-Bertelsen Jonathan H. Wardman René Villadsen Nanna MacAulay Transcriptional profiling of transport mechanisms and regulatory pathways in rat choroid plexus Fluids and Barriers of the CNS Cerebrospinal fluid Membrane transport CSF secretion RNA sequencing RNAseq Bioinformatics |
| title | Transcriptional profiling of transport mechanisms and regulatory pathways in rat choroid plexus |
| title_full | Transcriptional profiling of transport mechanisms and regulatory pathways in rat choroid plexus |
| title_fullStr | Transcriptional profiling of transport mechanisms and regulatory pathways in rat choroid plexus |
| title_full_unstemmed | Transcriptional profiling of transport mechanisms and regulatory pathways in rat choroid plexus |
| title_short | Transcriptional profiling of transport mechanisms and regulatory pathways in rat choroid plexus |
| title_sort | transcriptional profiling of transport mechanisms and regulatory pathways in rat choroid plexus |
| topic | Cerebrospinal fluid Membrane transport CSF secretion RNA sequencing RNAseq Bioinformatics |
| url | https://doi.org/10.1186/s12987-022-00335-x |
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