Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA387031 | ENA |
REPOSITORIES: ENA
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Project description:The choroid plexus produces cerebrospinal fluid (CSF) by transport of electrolytes and water from the vasculature to the brain ventricles. The choroid plexus plays additional roles in brain development and homeostasis by secreting neurotrophic molecules, and by serving as a CSF-blood barrier and immune interface. Prior studies have identified transporters on the epithelial cells that transport water and ions into the ventricles and tight junctions involved in the CSF-blood barrier. Yet, how the choroid plexus epithelial cells maintain the brain ventricle system and control brain physiology remain unresolved. To provide novel insights into the physiological roles of the choroid plexus, we use juvenile and adult zebrafish as model systems. Upon histological and transcriptomic analyses, we first identified that the zebrafish choroid plexus is highly conserved with the mammalian choroid plexus and that it expresses all transporters necessary for CSF secretion. Using novel genetic lines, we also identified that the choroid plexus secretes proteins into the CSF. Next, we generated a transgenic line allowing us to ablate specifically the epithelial cells in the choroid plexus. Using the ablation system, we identified a reduction of the ventricular sizes, but no alterations of the CSF-blood barrier. Altogether, our findings identified that the zebrafish choroid plexus is evolutionarily conserved and critical for maintaining the size and homeostasis of the brain ventricles.
2024-05-06 | GSE246851 | GEO
Project description:The central nervous system manifestations of systemic lupus erythematosus (SLE) remain poorly understood, confounding physician treatment options and leaving patients with little options beyond empirical remedies. We utilized a well-established model of both the systemic and neuropsychiatric manifestations of SLE in an attempt to further understand which immune effectors may be responsible for central nervous system (CNS) disease. We found that a mixed cellular infiltrate in the choroid plexus of these mice represented a tertiary lymphoid structure with in-situ somatic hypermutation and class switch recombination. We further found that this process was driven by cytokine signaling sourced within the CNS that could be abrogated by treatment with biological therapeutics. Therefore, inconsistencies in previous work to determine which neuropathic autoantibodies are involved in the progression of neuropsychiatric lupus may have been lacking, as the source of these autoantibodies are intra-cranial, with limited systemic distribution.
2019-06-17 | GSE99030 | GEO
Project description:These tissue were harvested to complement and extend the studies that generated GSE23093. They served 3 purposes; 1) identify genes important to choroid plexus function and compare them with those important for meninges and associated vasculature (MAV) function, 2) determine genes in the choroid plexus and sensitivity hyperthermia and amphetamine toxicity, 3) identify the important gene expression changes related to the immune system in MAV, choroid plexus and trunk' blood Gene mRNA expression patterns in choroid plexus and trunk blood were determined under control conditions as well as after (3 hr and 1day) exposure to either environmentally-induced hyperthermia or neurotoxic doses of amphetamine. This data was analyzed and compared to data from meninges and associated vasculature previously deposited in GEO. The data gathered under control conditions was used to further understand how the choroid plexus and meninges and associated vasculature might function to generate and regulate the cerebrospinal fluid. The expression patterns in the choroid plexus after environmentally-induced hyperthermia or neurotoxic doses of amphetamine was determine its damage and protective responses. The expression patterns after environmentally-induced hyperthermia or neurotoxic doses of amphetamine were compared among choroid plexus, meninges and associated vasculature and blood were analyzed to determine immune system responses.
2012-08-01 | E-GEOD-29733 | biostudies-arrayexpress
Project description:Laser capture microdissected choroid plexuses were obtained and expression arrays were generated to investigate gene expression in wt and ApoE choroid plexuses; the choroid plexus forms the cerebrospinal fluid, the cerebrospinal fliod barrier, functions as the major gateway for blood-born leukocytes to enter the brain in degenerative and inflammatory brain diseases, and the principal neuroimmune interface in the brain. We found lipid deposits in the aged choroid plexus of hyperlipidemic mice but none in the wt control choroid plexuses. Here, we studied the functional impact and gene epressions in wt and ApoE-deficient choroid plexuses.
2018-11-20 | GSE85775 | GEO
Project description:Laser capture microdissected choroid plexuses were obtained and expression arrays were generated to investigate gene expression in ApoE-Knockin choroid plexuses; the choroid plexus forms the cerebrospinal fluid, the cerebrospinal fliod barrier, functions as the major gateway for blood-born leukocytes to enter the brain in degenerative and inflammatory brain diseases, and the principal neuroimmune interface in the brain. We found lipid deposits in the aged choroid plexus of hyperlipidemic ApoE4-Knockin mice but none in normolipidemic ApoE4-Knockin or normolipidemic or hyperlipidemic ApoE3-Knockin control choroid plexuses. Here, we studied the functional impact and gene epressions these choroid plexuses.
2018-11-20 | GSE85774 | GEO
Project description:Gene expression profiles generated from human tumor cells laser-microdissected from surgical samples of seven choroid plexus papillomas (Grade I WHO) as eight samples of epithelial cells lasermicrodissected from normal choroid plexus obtained at autopsy. Choroid plexus tumors are rare pediatric brain tumors derrived from the choroid plexus epithelium. Gene expression profiles of lasermicrodissected tumor cells from 7 individual choroid plexus tumor samples obtained at surgery were compared to gene expression profiles from non-neoplastic choroid plexus epithelial cells lasermicrodissected from normal non-neoplastic choroid plexus obtained at autopsy (Am J Surg Pathol. 2006 Jan;30(1):66-74.) in order to identfy genes differentially expressed in choroid plexus tumor cells.
2009-02-01 | E-GEOD-14098 | biostudies-arrayexpress
Project description:Why individuals with Down Syndrome (DS, trisomy 21) are particularly susceptible to SARS-CoV-2 induced disease remains largely unclear. The choroid plexus secrets the cerebrospinal fluid and strongly expresses the ACE2 receptor and the chromosome 21 encoded TMPRSS2 protease. To investigate the role of the choroid plexus in SARS-CoV-2 central nervous system infection in DS, we established a new type of brain organoid from DS and isogenic euploid control iPSC that consists of a core of appropriately patterned functional cortical neuronal cell types that is surrounded by a patent and functional choroid plexus (CPCOs). Remarkably, DS-CPCOs not only recapitulated abnormal features of DS cortical development but also revealed defects in ciliogenesis and epithelial cell polarity of the developing choroid plexus. We next demonstrate that the choroid plexus layer facilitates SARS-CoV-2 replication and infection of cortical neuronal cells, and that this is increased in DS-CPCOs. We further show that inhibition of TMPRSS2 activity in DS-CPCOs inhibits SARS-CoV-2 infectivity. We conclude that CPCOs are a useful model for dissecting the role of the choroid plexus in euploid and DS forebrain development and enables screening for therapeutics that can inhibit SARS-CoV-2 induced neuro-pathogenesis.
2023-10-16 | GSE208440 | GEO
Project description:Why individuals with Down Syndrome (DS, trisomy 21) are particularly susceptible to SARS-CoV-2 induced disease remains largely unclear. The choroid plexus secrets the cerebrospinal fluid and strongly expresses the ACE2 receptor and the chromosome 21 encoded TMPRSS2 protease. To investigate the role of the choroid plexus in SARS-CoV-2 central nervous system infection in DS, we established a new type of brain organoid from DS and isogenic euploid control iPSC that consists of a core of appropriately patterned functional cortical neuronal cell types that is surrounded by a patent and functional choroid plexus (CPCOs). Remarkably, DS-CPCOs not only recapitulated abnormal features of DS cortical development but also revealed defects in ciliogenesis and epithelial cell polarity of the developing choroid plexus. We next demonstrate that the choroid plexus layer facilitates SARS-CoV-2 replication and infection of cortical neuronal cells, and that this is increased in DS-CPCOs. We further show that inhibition of TMPRSS2 activity in DS-CPCOs inhibits SARS-CoV-2 infectivity. We conclude that CPCOs are a useful model for dissecting the role of the choroid plexus in euploid and DS forebrain development and enables screening for therapeutics that can inhibit SARS-CoV-2 induced neuro-pathogenesis.
2022-07-26 | GSE208575 | GEO
Project description:Immune response following CNS disease and injury comprises three different compartments, parenchymal, perivascular and blood involving specialized immune cells. Microglia are the major immune cell residing in the CNS parenchymal compartment but together with other macrophages which are residing in the non-parenchymal structures such as perivascular spaces, leptomeninges and choroid plexus constitute the total macrophage population of the CNS. While the homeostatic functions of these specialized macrophages in not very well understood, evidence shows that these macrophages at the blood-brain interface might involve immune-surveillance and establish a gate way for the recruitment of peripheral immune cells in to the CNS in response to the pathological stimuli. In humans and rats these macrophages identified exclusively by the high levels of scavenger receptor CD163
2019-06-30 | GSE99206 | GEO
Project description:Choroid plexus secretes cerebrospinal fluid important for brain development and homeostasis. The OTX2 homeoprotein is critical for choroid plexus development and remains highly expressed in adult choroid plexus. Through RNA sequencing analyses of constitutive and conditional knockdown adult mouse models, we reveal putative roles for OTX2 in choroid plexus function, including cell signaling and adhesion, and show that it regulates the expression of factors secreted into cerebrospinal fluid, notably transthyretin. We also show that Otx2 expression impacts choroid plexus immune and stress responses, and also affects splicing which leads to changes in mRNA isoforms of proteins implicated in oxidative stress response and DNA repair. Through mass spectrometry analysis of OTX2 protein partners in the choroid plexus, and in known non-cell autonomous target regions such as visual cortex and subventricular zone, we identified putative targets involved in cell adhesion, chromatin structure and RNA processing. Thus, OTX2 retains important roles in choroid plexus function and brain homeostasis throughout life.
2021-08-31 | GSE157386 | GEO