Ablation of placental REST deregulates fetal brain metabolism and impacts gene expression of the offspring brain at the postnatal and adult stages DOI
Maliha Islam,

Ananya Samal,

Daniel J. Davis

и другие.

The FASEB Journal, Год журнала: 2023, Номер 38(1)

Опубликована: Дек. 9, 2023

Abstract In this study, the transcriptional repressor REST (Repressor Element 1 Silencing Transcription factor) was ablated in mouse placenta to investigate molecular and cellular impacts on offspring brain at different life stages. Ablation of placental deregulated several metabolites, including glucose lactate that fuel energy, vitamin C (ascorbic acid) functions epigenetic programming during postnatal development, glutamate creatine help respond stress conditions adult life. Bulk RNA‐seq analysis showed a lack persistently altered multiple transport genes, those related oxygen transportation brain. While metabolic genes were impacted brain, response activated DNA methylation also due loss REST, but sex‐biased manner. Single‐nuclei specific cell types particularly choroid plexus ependyma, which play critical roles producing cerebrospinal fluid maintaining homeostasis, significantly REST. These cells significant differential expression associated with metabotropic (G coupled protein) ionotropic (ligand‐gated ion channel) receptors, suggesting an impact ablation glutamatergic signaling The study expands our understanding influences

Язык: Английский

Deconstructing the functional neuroanatomy of the choroid plexus: an ontogenetic perspective for studying neurodevelopmental and neuropsychiatric disorders DOI Creative Commons
Byron K.Y. Bitanihirwe, Paulo Lizano, Tsung‐Ung W. Woo

и другие.

Molecular Psychiatry, Год журнала: 2022, Номер 27(9), С. 3573 - 3582

Опубликована: Май 26, 2022

Abstract The choroid plexus (CP) is a delicate and highly vascularized structure in the brain comprised of dense network fenestrated capillary loops that help synthesis, secretion circulation cerebrospinal fluid (CSF). This unique neuroanatomical arachnoid villi stemming from frond-like surface projections—that protrude into lumen four cerebral ventricles—providing key source nutrients to parenchyma addition serving as ‘sink’ for central nervous system metabolic waste. In fact, functions CP are often described being analogous those liver kidney. Beyond forming barrier/interface between blood CSF compartments, has been identified modulator leukocyte trafficking, inflammation, cognition, circadian rhythm gut brain-axis. recent years, advances molecular biology techniques neuroimaging along with use sophisticated animal models have played an integral role shaping our understanding how CP–CSF changes relation maturation neural circuits during critical periods development. this article we provide ontogenetic perspective review experimental evidence implicating pathophysiology neurodevelopmental neuropsychiatric disorders.

Язык: Английский

Процитировано

37

Experimental approaches for manipulating choroid plexus epithelial cells DOI Creative Commons
Ahram Jang, Maria K. Lehtinen

Fluids and Barriers of the CNS, Год журнала: 2022, Номер 19(1)

Опубликована: Май 26, 2022

Choroid plexus (ChP) epithelial cells are crucial for the function of blood-cerebrospinal fluid barrier (BCSFB) in developing and mature brain. The ChP is considered primary source regulator CSF, secreting many important factors that nourish It also performs CSF clearance functions including removing Amyloid beta potassium. As such, a promising target gene drug therapy neurodevelopmental neurological disorders central nervous system (CNS). This review describes current successful emerging experimental approaches targeting cells. We highlight methodological strategies to specifically these gain or loss vivo. cover both genetic models viral delivery systems. Additionally, several lines reporters access epithelia reviewed. Finally, we discuss exciting new approaches, such as chemical activation transplantation engineered elaborate on fundamental secretion outline paving way clinical applications.

Язык: Английский

Процитировано

26

The vasculature of neurogenic niches: Properties and function DOI Creative Commons
Andromachi Karakatsani, María I. Álvarez-Vergara, Carmen Ruiz de Almodóvar

и другие.

Cells and Development, Год журнала: 2023, Номер 174, С. 203841 - 203841

Опубликована: Апрель 14, 2023

In the adult rodent brain, neural stem cells (NSCs) reside in subventricular zone (SVZ) of lateral ventricles and subgranular (SGZ) hippocampus. these areas, NSCs their progeny integrate intrinsic signals extrinsic cues provided by microenvironment that control behavior. The vasculature SVZ SGZ, choroid plexus (ChP) SVZ, have emerged as critical compartments neurogenic niches they provide a rich repertoire to regulate NSC quiescence, proliferation, self-renewal differentiation. Physical contact between blood vessels is also feature within supports different processes such migration vesicle transport. this review, we description brain both cell niches, highlighting main properties role each niche. We summarize current understanding how vessel- ChP-derived influence behavior physiological adulthood, well upon aging.

Язык: Английский

Процитировано

14

Regulation of choroid plexus development and its functions DOI Creative Commons
Petra Kompaníková, Vı́tězslav Bryja

Cellular and Molecular Life Sciences, Год журнала: 2022, Номер 79(6)

Опубликована: Май 19, 2022

Abstract The choroid plexus (ChP) is an extensively vascularized tissue that protrudes into the brain ventricular system of all vertebrates. This highly specialized structure, consisting polarized epithelial sheet and underlying stroma, serves a spectrum functions within central nervous (CNS), most notably production cerebrospinal fluid (CSF). cells ChP have competence to tightly modulate biomolecule composition CSF, which acts as milieu functionally connecting with other structures. review aims eloquently summarize current knowledge about development ChP. We describe mechanisms control its early specification from roof plate followed by formation proliferative regions—cortical hem rhombic lips—feeding later Next, we summarized on maturation morphological cellular diversity. Furthermore, attempted currently available battery molecular markers mouse strains for research ChP, identified some technological shortcomings must be overcome accelerate field. Overall, principle this highlight intriguing surprisingly poorly known structure vital function whole CNS. believe our summary will increase interest in further studies aim principles guiding tissue.

Язык: Английский

Процитировано

23

Choroid Plexus: The Orchestrator of Long-Range Signalling Within the CNS DOI Open Access
Karol Kaiser, Vı́tězslav Bryja

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(13), С. 4760 - 4760

Опубликована: Июль 4, 2020

Cerebrospinal fluid (CSF) is the liquid that fills brain ventricles. CSF represents not only a mechanical protection but also rich source of signalling factors modulating diverse processes during development and adulthood. The choroid plexus (CP) major as such it has recently emerged an important mediator extracellular within brain. Growing interest in CP revealed its capacity to release broad variety bioactive molecules that, via CSF, regulate across whole central nervous system (CNS). Moreover, been recognized sensor, responding altered composition associated with changes patterns CNS activity. In this review, we summarize recent advances our understanding centre mediates long-range communication CNS. By providing detailed account secretory repertoire, describe how contributes regulation environment—in context both embryonal well adult We highlight role regulator function acts CSF-mediated signalling. Further studies CP–CSF hold potential provide key insights into biology CNS, implications for better treatment neuropathological conditions.

Язык: Английский

Процитировано

25

L-arginine mitigates choroid plexus changes in Alzheimer’s disease rat model via oxidative/inflammatory burden and behavioral modulation DOI
Wael Amin Nasr El‐Din, Islam Omar Abdel Fattah

Tissue and Cell, Год журнала: 2024, Номер 91, С. 102572 - 102572

Опубликована: Сен. 24, 2024

Язык: Английский

Процитировано

3

Current progress and challenges in the development of brain tissue models: How to grow up the changeable brain in vitro? DOI Creative Commons
А. Б. Салмина, Olga P. Alexandrova, Anton S. Averchuk

и другие.

Journal of Tissue Engineering, Год журнала: 2024, Номер 15

Опубликована: Янв. 1, 2024

In vitro modeling of brain tissue is a promising but not yet resolved problem in modern neurobiology and neuropharmacology. Complexity the structure diversity cell-to-cell communication (patho)physiological conditions make this task almost unachievable. However, establishment novel models would ultimately lead to better understanding development-associated or experience-driven plasticity, designing efficient approaches restore aberrant functioning. The main goal review summarize available data on methodological that are currently use, identify most prospective trends development neurovascular unit, blood-brain barrier, blood-cerebrospinal fluid neurogenic niche models. manuscript focuses regulation adult neurogenesis, cerebral microcirculation fluids dynamics should be reproduced 4D mimic its alterations pathology. We discuss critical for studying deciphering individual person-specific trajectory aging, testing new drug candidates

Язык: Английский

Процитировано

2

OTX2 Homeoprotein Functions in Adult Choroid Plexus DOI Open Access
Anabelle Planques, Vanessa Oliveira Moreira,

David Benacom

и другие.

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(16), С. 8951 - 8951

Опубликована: Авг. 19, 2021

The choroid plexus is an important blood barrier that secretes cerebrospinal fluid, which essential for embryonic brain development and adult homeostasis. OTX2 homeoprotein a transcription factor critical remains highly expressed in plexus. Through RNA sequencing analyses of constitutive conditional knockdown mouse models, we reveal putative functional roles function, including cell signaling adhesion, show regulates the expression factors are secreted into notably transthyretin. We also Otx2 impacts immune stress responses, affects splicing, leading to changes mRNA isoforms proteins implicated oxidative response DNA repair. mass spectrometry analysis protein partners plexus, known non-cell-autonomous target regions, such as visual cortex subventricular zone, identify targets involved chromatin structure, processing. Thus, retains regulating function homeostasis throughout life.

Язык: Английский

Процитировано

10

Choroid plexus morphology in schizophrenia and early-stage psychosis: A cross-sectional study DOI Creative Commons

Gina Brunner,

Ruchika Gajwani, Joachim Groß

и другие.

Schizophrenia Research, Год журнала: 2024, Номер 275, С. 107 - 114

Опубликована: Дек. 17, 2024

The choroid plexus is an important structure within the ventricular system. Schizophrenia has been associated with morphological changes to but presence and extent of alterations at different illness stages unclear. We examined volumes in participants clinical high-risk for psychosis (N = 110), first-episode 37), schizophrenia 28), 38) non-clinical controls 75). Automated segmentation (Gaussian mixture model) was used estimate from T1 magnetic resonance (MR) images. then conducted a linear model Bayes factor analysis investigate group differences. In addition, relationship between characteristics assessed. patients were characterized by increased volume while showed no differences volumes. However, did not significantly differ when controlling volume. Finally, group. Our findings suggest that are specific early-stage psychosis. Previously reported abnormalities could be explained

Язык: Английский

Процитировано

1

The choroid plexus: a door between the blood and the brain for tissue-type plasminogen activator DOI Creative Commons

Vincent Zuba,

Jonathane Furon,

Mathys Bellemain-Sagnard

и другие.

Fluids and Barriers of the CNS, Год журнала: 2022, Номер 19(1)

Опубликована: Окт. 15, 2022

In the vascular compartment, serine protease tissue-type plasminogen activator (tPA) promotes fibrinolysis, justifying its clinical use against vasculo-occlusive diseases. Accumulating evidence shows that circulating tPA (endogenous or exogenous) also controls brain physiopathological processes, like cerebrovascular reactivity, blood-brain barrier (BBB) homeostasis, inflammation and neuronal fate. Whether this occurs by direct actions on parenchymal cells and/or indirectly via barriers between blood central nervous system (CNS) remains unclear. Here, we postulated can reach parenchyma blood-cerebrospinal fluid (BCSFB), relies choroid plexus (CP) epithelial (CPECs).We produced various reporter fusion proteins to track in primary cultures of CPECs, CP explants vivo mice. We investigated mechanisms underlying transport across BCSFB, with pharmacological molecular approaches.We first demonstrated be internalized CPECs ex CPs explants. vivo, both at their basal apical sides. After intra-vascular administration, cerebral spinal (CSF) parenchyma. Further investigation allowed discovering transcytosis is mediated Low-density-Lipoprotein Related Protein-1 (LRP1) expressed surface depends finger domain tPA. Interestingly, albumin, which has a size comparable tPA, does not normally cross CPs, but switches transportable form when grafted tPA.These findings provide new insights how parenchyma, open therapeutic avenues for CNS disorders.

Язык: Английский

Процитировано

6