Choroid plexus trophic factors in the developing and adult brain

Arnaud, Karen; Nardo, Ariel A. Di

doi:10.1007/s11515-016-1401-7

Cited by 5 publications

(4 citation statements)

References 101 publications

(105 reference statements)

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“…Structurally, the CP consists of a single layer of cuboidal epithelial cells connected by apical tight junctions that interfaces CSF and fenestrated capillaries forming the blood-CSF barrier (BCSFB) ( 16 ). Moreover, the CP has various other functions such as strict regulation of transport systems that modulate CSF composition by allowing passage of nutrients such as glucose, lipids and proteins, solutes and inflammatory cells ( 16 ), as well as producing growth factors and hormones involved with development and maintenance of brain function ( 17 ). Previous research has shown that dysfunction of the CP and ventriculomegaly are involved in the pathogenesis of neurodegenerative diseases including Alzheimer’s disease ( 18 – 20 ) and multiple sclerosis ( 21 – 23 ).…”

Section: Introductionmentioning

confidence: 99%

Differences in the choroid plexus volume and microstructure are associated with body adiposity

2022

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The choroid plexus (CP) is a cerebral structure located in the ventricles that functions in producing most of the brain’s cerebrospinal fluid (CSF) and transporting proteins and immune cells. Alterations in CP structure and function has been implicated in several pathologies including aging, multiple sclerosis, Alzheimer’s disease, and stroke. However, identification of changes in the CP remains poorly characterized in obesity, one of the main risk factors of neurodegeneration, including in the absence of frank central nervous system alterations. Our goal here was to characterize the association between obesity, measured by the body mass index (BMI) or waist circumference (WC) metrics, and CP microstructure and volume, assessed using advanced magnetic resonance imaging (MRI) methodology. This cross-sectional study was performed in the clinical unit of the National Institute on Aging and included a participant population of 123 cognitively unimpaired individuals spanning the age range of 22 – 94 years. Automated segmentation methods from FreeSurfer were used to identify the CP structure. Our analysis included volumetric measurements, quantitative relaxometry measures (T1 and T2), and the diffusion tensor imaging (DTI) measure of mean diffusivity (MD). Strong positive associations were observed between WC and all MRI metrics, as well as CP volume. When comparing groups based on the established cutoff point by the National Institutes of Health for WC, a modest difference in MD and a significant difference in T1 values were observed between obese and lean individuals. We also found differences in T1 and MD between obese and overweight individuals as defined using the BMI cutoff. We conjecture that these observations in CP volume and microstructure are due to obesity-induced inflammation, diet, or, very likely, dysregulations in leptin binding and transport. These findings demonstrate that obesity is strongly associated with a decline in CP microstructural integrity. We expect that this work will lay the foundation for further investigations on obesity-induced alterations in CP structure and function.

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Section: Introductionmentioning

confidence: 99%

Differences in the choroid plexus volume and microstructure are associated with body adiposity

2022

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“…The choroid plexus (CP) modulates brain homeostasis through several processes including cerebral spinal fluid (CSF) secretion and expression of various proteins (Lun et al, 2015;Hofman and Chen, 2016). Specifically, the CP secretes numerous neurotrophic factors implicated in neurogenesis, vascularity regulation, maintenance of brain function, and signaling molecules including neuroinflammatory cytokines (Arnaud and Di Nardo, 2016;Mazucanti et al, 2019). The ubiquitous multifunctional role of the CP was highlighted in a recent study by Mazucanti et al (2019), indicating that insulin is produced in the CP and modulated by serotonin.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Age-Related Differences in the Human Choroid Plexus Volume, Microstructural Integrity, and Blood Perfusion Using Multiparameter Magnetic Resonance Imaging

Alisch

Kiely

Triebswetter

et al. 2021

Front. Aging Neurosci.

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The choroid plexus (CP) is an important cerebral structure involved in cerebrospinal fluid production and transport of solutes into the brain. Recent studies have uncovered the involvement of the CP in neurological disorders such as Alzheimer’s disease and multiple sclerosis. However, our understanding of human age-related microstructural and functional changes in the CP with aging and neuropathology is limited. In this cross-sectional study, we investigated age and sex differences in the CP structure and function using advanced quantitative magnetic resonance imaging methodology in a large cohort (n = 155) of cognitively unimpaired individuals over a wide age range between 21 and 94 years. Our analysis included volumetric measurements, relaxometry measures (T1 and T2), diffusion tensor imaging (DTI) measures of fractional anisotropy (FA) and mean diffusivity (MD), as well as measures of cerebral blood flow (CBF). Our results revealed that CP volume was increasing with advancing age. We conjecture that this novel observation is likely attributed to alterations in the CP microstructure or function as well as to ventriculomegaly. Indeed, we also found that CBF was lower with advanced age, while, consistent with previous studies, T1, T2 and MD were higher, and FA was lower with advanced age. We attribute these functional and microstructural differences to a deteriorated CP structural integrity with aging. Furthermore, our relaxometry and DTI measures were found to be associated with differences in blood perfusion revealing lower microstructural integrity with lower CBF. Finally, in agreement with literature, sex-related differences in MD and CBF were statistically significant. This work lays the foundation for ongoing investigation of the involvement of CP in neurodegeneration.

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“…CSF is produced by the choroid plexus ependymal cells in the ventricles, which selectively filter nutrients and electrolytes from blood plasma. In addition, CSF is rich in trophic factors synthesized in the choroid plexus, including brain-derived neurotrophic factor (BDNF), glia-derived neurotrophic factor (GDNF), nerve growth factor, fibroblast growth factor (FGF), epithelial growth factor (EGF), transforming growth factor-β, platelet-derived growth factor, insulin growth factor (IGF), vascular endothelial growth factor, and the homeoprotein Otx2 (14)(15)(16). CSF biochemistry is thus different from plasma (14) and creates a unique extracellular environment in the CNS that is not found anywhere else in the body.…”

Section: Introductionmentioning

confidence: 99%

Human cerebrospinal fluid affects chemoradiotherapy sensitivities in tumor cells from patients with glioblastoma

Stringer,

De Silva,

Greenberg

et al. 2023

Sci. Adv.

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Cancers in the central nervous system resist therapies effective in other cancers, possibly due to the unique biochemistry of the human brain microenvironment composed of cerebrospinal fluid (CSF). However, the impact of CSF on cancer cells and therapeutic efficacy is unknown. Here, we examined the effect of human CSF on glioblastoma (GBM) tumors from 25 patients. We found that CSF induces tumor cell plasticity and resistance to standard GBM treatments (temozolomide and irradiation). We identified nuclear protein 1 (NUPR1), a transcription factor hampering ferroptosis, as a mediator of therapeutic resistance in CSF. NUPR1 inhibition with a repurposed antipsychotic, trifluoperazine, enhanced the killing of GBM cells resistant to chemoradiation in CSF. The same chemo-effective doses of trifluoperazine were safe for human neurons and astrocytes derived from pluripotent stem cells. These findings reveal that chemoradiation efficacy decreases in human CSF and suggest that combining trifluoperazine with standard care may improve the survival of patients with GBM.

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Choroid plexus trophic factors in the developing and adult brain

Cited by 5 publications

References 101 publications

Differences in the choroid plexus volume and microstructure are associated with body adiposity

Differences in the choroid plexus volume and microstructure are associated with body adiposity

Characterization of Age-Related Differences in the Human Choroid Plexus Volume, Microstructural Integrity, and Blood Perfusion Using Multiparameter Magnetic Resonance Imaging

Human cerebrospinal fluid affects chemoradiotherapy sensitivities in tumor cells from patients with glioblastoma

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