A molecular characterization of the choroid plexus and stress-induced gene regulation
- PMID: 22781172
- PMCID: PMC3410626
- DOI: 10.1038/tp.2012.64
A molecular characterization of the choroid plexus and stress-induced gene regulation
Abstract
The role of the choroid plexus (CP) in brain homeostasis is being increasingly recognized and recent studies suggest that the CP has a more important role in physiological and pathological brain functions than currently appreciated. To obtain additional insight on the CP function, we performed a proteomics and transcriptomics characterization employing a combination of high resolution tandem mass spectrometry and gene expression analyses in normal rodent brain. Using multiple protein fractionation approaches, we identified 1400 CP proteins in adult CP. Microarray-based comparison of CP gene expression with the kidney, cortex and hippocampus showed significant overlap between the CP and the kidney. CP gene profiles were validated by in situ hybridization analysis of several target genes including klotho, CLIC 6, OATP 14 and Ezrin. Immunohistochemical analyses were performed for CP and enpendyma detection of several target proteins including cytokeratin, Rab7, klotho, tissue inhibitor of metalloprotease 1 (TIMP1), MMP9 and glial fibrillary acidic protein (GFAP). The molecular functions associated with various proteins of the CP proteome indicate that it is a blood-cerebrospinal fluid (CSF) barrier that exhibits high levels of metabolic activity. We also analyzed the gene expression changes induced by stress, an exacerbating factor for many illnesses, particularly mood disorders. Chronic stress altered the expression of several genes, downregulating 5HT2C, glucocorticoid receptor and the cilia genes IFT88 and smoothened while upregulating 5HT2A, BDNF, TNFα and IL-1b. The data presented here attach additional significance to the emerging importance of CP function in brain health and CNS disease states.
Figures
Similar articles
-
Sex-Related Differences in Rat Choroid Plexus and Cerebrospinal Fluid: A cDNA Microarray and Proteomic Analysis.J Neuroendocrinol. 2016 Jan;28(1). doi: 10.1111/jne.12340. J Neuroendocrinol. 2016. PMID: 26606900
-
Comparative transcriptomics of choroid plexus in Alzheimer's disease, frontotemporal dementia and Huntington's disease: implications for CSF homeostasis.Fluids Barriers CNS. 2018 May 31;15(1):18. doi: 10.1186/s12987-018-0102-9. Fluids Barriers CNS. 2018. PMID: 29848382 Free PMC article.
-
Gene expression and functional annotation of human choroid plexus epithelium failure in Alzheimer's disease.BMC Genomics. 2015 Nov 16;16:956. doi: 10.1186/s12864-015-2159-z. BMC Genomics. 2015. PMID: 26573292 Free PMC article.
-
The choroid plexus-cerebrospinal fluid system: from development to aging.Curr Top Dev Biol. 2005;71:1-52. doi: 10.1016/S0070-2153(05)71001-2. Curr Top Dev Biol. 2005. PMID: 16344101 Review.
-
A balanced view of choroid plexus structure and function: Focus on adult humans.Exp Neurol. 2015 May;267:78-86. doi: 10.1016/j.expneurol.2015.02.032. Epub 2015 Mar 4. Exp Neurol. 2015. PMID: 25747036 Review.
Cited by 24 articles
-
Choroid plexus and the blood-cerebrospinal fluid barrier in disease.Fluids Barriers CNS. 2020 May 6;17(1):35. doi: 10.1186/s12987-020-00196-2. Fluids Barriers CNS. 2020. PMID: 32375819 Free PMC article. Review.
-
Podoplanin Gene Disruption in Mice Promotes in vivo Neural Progenitor Cells Proliferation, Selectively Impairs Dentate Gyrus Synaptic Depression and Induces Anxiety-Like Behaviors.Front Cell Neurosci. 2020 Jan 15;13:561. doi: 10.3389/fncel.2019.00561. eCollection 2019. Front Cell Neurosci. 2020. PMID: 32009902 Free PMC article.
-
Proteomic analysis of cerebrospinal fluid extracellular vesicles reveals synaptic injury, inflammation, and stress response markers in HIV patients with cognitive impairment.J Neuroinflammation. 2019 Dec 5;16(1):254. doi: 10.1186/s12974-019-1617-y. J Neuroinflammation. 2019. PMID: 31805958 Free PMC article.
-
Klotho controls the brain-immune system interface in the choroid plexus.Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):E11388-E11396. doi: 10.1073/pnas.1808609115. Epub 2018 Nov 9. Proc Natl Acad Sci U S A. 2018. PMID: 30413620 Free PMC article.
-
Cross-talks between the kidneys and the central nervous system in multiple sclerosis.Caspian J Intern Med. 2018 Summer;9(3):206-210. doi: 10.22088/cjim.9.3.206. Caspian J Intern Med. 2018. PMID: 30197763 Free PMC article. Review.
References
-
- Johanson CE. The Choroid Plexus-CSF Nexus, Gateway to the brainIn: Conn MP (ed).Neuroscience in Medicine Humana Press Inc: Totowa, NJ; 2003165–195.
-
- Richardson SJ. Cell and molecular biology of transthyretin and thyroid hormones. Int Rev Cytol. 2007;258:137–193. - PubMed
-
- Spector R, Johanson C. Micronutrient and urate transport in choroid plexus and kidney: implications for drug therapy. Pharm Res. 2006;23:2515–2524. - PubMed
Publication types
MeSH terms
Grant support
LinkOut - more resources
-
Full Text Sources
-
Other Literature Sources
-
Medical
-
Research Materials
-
Miscellaneous