Development and functions of the choroid plexus–cerebrospinal fluid system

Lun, Melody P.; Monuki, Edwin S.; Lehtinen, Maria K.

doi:10.1038/nrn3921

Cited by 487 publications

(417 citation statements)

References 158 publications

(181 reference statements)

Supporting

Mentioning

400

Contrasting

Unclassified

Order By: Relevance

“…Choroidal BCSFB dysfunction underlies leukocyte infiltration, reduced neurogenesis, and cognitive decline in many neurological diseases [43]. In the current study, we found orthopedic surgery significantly induced C3 deposition in the choroid plexus.…”

Section: Discussionsupporting

confidence: 51%

Complement activation contributes to perioperative neurocognitive disorders in mice

Xiong

Lü

Lin

et al. 2018

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundThe complement system plays an important role in many neurological disorders.Complement modulation, including C3/C3a receptor signaling, shows promising therapeutic effects on cognition and neurodegeneration. Yet, the implications for this pathway in perioperative neurocognitive disorders (PND) are not well established. Here, we evaluated the possible role for C3/C3a receptor signaling after orthopedic surgery using an established mouse model of PND.MethodsA stabilized tibial fracture surgery was performed in adult male C57BL/6 mice under general anesthesia and analgesia to induce PND-like behavior. Complement activation was assessed in the hippocampus and choroid plexus. Changes in hippocampal neuroinflammation, synapse numbers, choroidal blood-cerebrospinal fluid barrier (BCSFB) integrity, and hippocampal-dependent memory function were evaluated after surgery and treatment with a C3a receptor blocker.ResultsC3 levels and C3a receptor expression were specifically increased in hippocampal astrocytes and microglia after surgery. Surgery-induced neuroinflammation and synapse loss in the hippocampus were attenuated by C3a receptor blockade. Choroidal BCSFB dysfunction occurred 1 day after surgery and was attenuated by C3a receptor blockade. Administration of exogenous C3a exacerbated cognitive decline after surgery, whereas C3a receptor blockade improved hippocampal-dependent memory function.ConclusionsOrthopedic surgery activates complement signaling. C3a receptor blockade may be therapeutically beneficial to attenuate neuroinflammation and PND.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1292-4) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionsupporting

confidence: 51%

Complement activation contributes to perioperative neurocognitive disorders in mice

Xiong

Lü

Lin

et al. 2018

J Neuroinflammation

View full text Add to dashboard Cite

show abstract

“…The blood-CSF barrier (BCB) lies between the choroid plexus vessels in circumventricular organs (CVOs) and the CSF (Choi and Kim, 2008;Benarroch, 2011;Lun et al, 2015). The CVOs are found to be located around the cerebral ventricles, and the CVOs with BCB are characterized by lack of BBB properties (Choi and Kim, 2008;Benarroch, 2011).…”

Section: Downloaded Frommentioning

confidence: 99%

Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia

Nakagawa¹,

Chiba²

2016

Journal of Pharmacology and Experimental Therapeutics

View full text Add to dashboard Cite

Development of social cognition, a unique and high-order function, depends on brain maturation from childhood to adulthood in humans. Autism spectrum disorder (ASD) and schizophrenia have similar social cognitive deficits, although age of onset in each disorder is different. Pathogenesis of these disorders is complex and contains several features, including genetic risk factors, environmental risk factors, and sites of abnormalities in the brain. Although several hypotheses have been postulated, they seem to be insufficient to explain how brain alterations associated with symptoms in these disorders develop at distinct developmental stages. Development of ASD appears to be related to cerebellar dysfunction and subsequent thalamic hyperactivation in early childhood. By contrast, schizophrenia seems to be triggered by thalamic hyperactivation in late adolescence, whereas hippocampal aberration has been possibly initiated in childhood. One of the possible culprits is metal homeostasis disturbances that can induce dysfunction of blood-cerebrospinal fluid barrier. Thalamic hyperactivation is thought to be induced by microglia-mediated neuroinflammation and abnormalities of intracerebral environment. Consequently, it is likely that the thalamic hyperactivation triggers dysregulation of the dorsolateral prefrontal cortex for lower brain regions related to social cognition. In this review, we summarize the brain aberration in ASD and schizophrenia and provide a possible mechanism underlying social cognitive deficits in these disorders based on their distinct ages of onset.

show abstract

“…We then searched for the expression of GAS1 in pericytes. These cells directly surround the endothelial cells (Lun et al 2015b), and there is a report showing that the pericytes of the CP express the receptor for SHH and respond to it, at least during development (Nielsen and Dymecki 2010). We used the anti-neural/ glial antigen 2 (NG2)-antibody which marks oligodendrocyte progenitor cells and pericytes (Nielsen and Dymecki 2010).…”

Section: Discussionmentioning

confidence: 99%

“…The CP consists of an epithelial and a stromal layer, the first one is a monolayer of epithelial cells that surrounds a stromal layer mainly composed by fenestrated capillaries and to a lesser extent by other cell types (Lun et al 2015b). …”

Section: Gas1 Is Expressed In the Stroma Of The Choroid Plexusmentioning

confidence: 99%

GAS1 is present in the cerebrospinal fluid and is expressed in the choroid plexus of the adult rat

Ayala-Sarmiento

Estudillo

Pérez‐Sánchez

et al. 2016

Histochem Cell Biol

View full text Add to dashboard Cite

Growth arrest specific 1 (GAS1) is a GPI-anchored protein that inhibits proliferation when overexpressed in tumors but during development it promotes proliferation and survival of different organs and tissues. This dual ability is caused by its capacity to interact both by inhibiting the signaling induced by the glial cell line-derived neurotrophic factor and by facilitating the activity of the sonic hedgehog pathway. GAS1 is expressed as membrane bound in different organs and as a secreted form by glomerular mesangial cells. In the developing central nervous system, GAS1 is found in neural progenitors; however, it continues to be expressed in the adult brain. Here, we demonstrate that soluble GAS1 is present in the cerebrospinal fluid (CSF) and it is expressed in the choroid plexus (CP) of the adult rat, the main producer of CSF. Additionally, we confirm the presence of GAS1 in blood plasma and liver of the adult rat, the principal source of blood plasma proteins. The pattern of expression of GAS1 is perivascular in both the CP and the liver. In vitro studies show that the fibroblast cell line NIH/3T3 expresses one form of GAS1 and releases two soluble forms into the supernatant. Briefly, in the present work, we show the presence of GAS1 in adult rat body fluids focusing in the CSF and the CP, and suggest that secreted GAS1 exists as two different isoforms.

show abstract

Development and functions of the choroid plexus–cerebrospinal fluid system

Cited by 487 publications

References 158 publications

Complement activation contributes to perioperative neurocognitive disorders in mice

Complement activation contributes to perioperative neurocognitive disorders in mice

Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia

GAS1 is present in the cerebrospinal fluid and is expressed in the choroid plexus of the adult rat

Contact Info

Product

Resources

About