Choroid Plexus Enlargement Exacerbates White Matter Hyperintensity Growth through Glymphatic Impairment

Annals of Neurology, Journal Year: 2023, Volume and Issue: 94(1), P. 182 - 195

Published: March 27, 2023

Choroid plexus (CP) is a key regulator in cerebrospinal fluid production, but its contribution to glymphatic clearance function and association with white matter hyperintensity (WMH) remains unclear.This retrospective study included 2 prospective 3.0-T magnetic resonance imaging (MRI) cohorts. In cohort 1, patients indications for lumbar puncture underwent 3-dimensional T1-weighted sequence (3D-T1) before at 39 hours after intrathecal administration of contrast agent (glymphatic MRI). 2, WMH were enrolled from the CIRCLE had median follow-up time 1.4 years. CP lateral ventricles automatically segmented on T2 fluid-attenuated inversion recovery (FLAIR) 3D-T1, respectively. volume was expressed as ratio intracranial volume. Glymphatic measured signal percentage change baseline 8 brain locations based MRI first cohort, or noninvasive diffusion tensor image analysis along perivascular space (DTI-ALPS) index DTI second cohort.In total 52 included. Higher correlated slower rate all locations. 197 Baseline positively associated growth. Furthermore, DTI-ALPS partially mediated both load growth.Enlarged could be an indicator larger growth WMH, potentially involving impaired function. The exploration may provide novel perspective clarify mechanism pathogenesis, well other glymphatic-related disorders. ANN NEUROL 2023;94:182-195.

Language: Английский

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Sickness behaviour and depression: An updated model of peripheral-central immunity interactions

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 111, P. 202 - 210

Published: April 17, 2023

Current research into mood disorders indicates that circulating immune mediators participating in the pathophysiology of chronic somatic have potent influences on brain function. This paradigm has brought to fore use anti-inflammatory therapies as adjunctive standard antidepressant therapy improve treatment efficacy, particularly subjects do not respond medication. Such new practice requires biomarkers tailor these those most likely benefit but also validated mechanisms action describing interaction between peripheral immunity and function optimize target intervention. These are generally studied preclinical models try recapitulate human disease, MDD, through peripherally induced sickness behaviour. In this proposal paper, after an appraisal data rodent their adherence clinical cohorts, we put forward a modified model periphery-brain interactions goes beyond currently established view microglia cells drivers depression. Instead, suggest that, for patients with mild levels inflammation, barriers primary actors disease resistance. We then highlight gaps novel lines research.

Language: Английский

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Choroid plexus volume enlargement in first-episode antipsychotic-naïve schizophrenia

Schizophrenia, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 2, 2024

Abstract Investigation of the choroid plexus in schizophrenia has seen growing interest due to its role interaction between neuroinflammation and brain dysfunction. Most previous studies included treated long-term ill patients, while antipsychotics illness course might both affect plexus. Here, we recruited first-episode antipsychotic-naïve performed high-resolution structural scan manually extracted volume. Choroid volume was compared patients healthy controls after controlling for age, sex intracranial Age effects were examined on patient control groups respectively. In also correlation with measures cortical subcortical gray matter, white lateral ventricular as well symptom severity cognitive function. Schizophrenia showed significantly enlarged controls. positively correlated age only group found larger volumes males than females groups, did not differ groups. among measures. No significant clinical ratings or performance observed. Without potential confounding pharmacotherapy course, our findings indicated enlargement be an enduring trait schizophrenia.

Language: Английский

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Cognitive and inflammatory heterogeneity in severe mental illness: Translating findings from blood to brain

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 118, P. 287 - 299

Published: March 8, 2024

Recent findings link cognitive impairment and inflammatory-immune dysregulation in schizophrenia (SZ) bipolar (BD) spectrum disorders. However, heterogeneity translation between the periphery central (blood-to-brain) mechanisms remains a challenge. Starting with large SZ, BD healthy control cohort (n = 1235), we aimed to i) identify candidate peripheral markers 25) associated domains 9) elucidate heterogenous immune-cognitive patterns, ii) evaluate regulation of using human induced pluripotent stem cell (iPSC)-derived astrocytes neural progenitor cells 10), iii) marker messenger RNA expression leukocytes microarray available data from subsample main 776), RNA-sequencing deconvolution analysis postmortem brain samples 474) CommonMind Consortium (CMC). We identified transdiagnostic subgroups based on covariance (measures speed verbal learning) reflecting inflammatory response (CRP, sTNFR1, YKL-40), innate immune activation (MIF) extracellular matrix remodelling (YKL-40, CatS). Of there was considerable variance secretion YKL-40 iPSC-derived SZ compared HC. Further, provide evidence dysregulated genes encoding related signalling pathways high neuroinflammatory subgroup samples. Our suggest relationship activity impairment, highlight as potential functioning individuals severe mental illness.

Language: Английский

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Engineering choroid plexus-on-a-chip with oscillatory flow for modeling brain metastasis

Materials Today Bio, Journal Year: 2023, Volume and Issue: 22, P. 100773 - 100773

Published: Aug. 19, 2023

The human brain choroid plexus (ChP) is a highly organized secretory tissue with complex vascular system and epithelial layers in the ventricles of brain. ChP body's principal source cerebrospinal fluid (CSF); it also functions as barrier to separate blood from CSF, because movement CSF through body pulsatile nature. Thus far, has been challenging recreate specialized features dynamics physiologically relevant microenvironment. In this study, we recapitulated structure by developing microfluidic chip accordance established design rules. Furthermore, used image processing analysis mimic flow within rlcking system; hydrogel containing laminin extracellular matrix (ECM). Human cells were cultured ChP-on-a-chip vivo-like dynamic an engineered ECM. key characteristics capillaries, layer, secreted components recreated adjusted microenvironment our ChP-on-a-chip. drug screening capabilities device observed responses breast cancer that had spread ChP. immune device, demonstrated motility cytotoxic effects macrophages, which are most prevalent Our will facilitate elucidation pathophysiology support development therapeutics treat cancers have metastasized into

Language: Английский

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Peripheral inflammatory subgroup differences in anterior Default Mode network and multiplex functional network topology are associated with cognition in psychosis

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 114, P. 3 - 15

Published: July 27, 2023

Language: Английский

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Brain‐derived subgroups of bipolar II depression associate with inflammation and choroid plexus morphology

Psychiatry and Clinical Neurosciences, Journal Year: 2023, Volume and Issue: 77(11), P. 613 - 621

Published: Aug. 19, 2023

Elevated inflammation and larger choroid plexus (ChP) volume has been previously identified in mood disorders. Connections between inflammation, ChP, clinical symptoms bipolar II depression (BDII-D) are unclear. Data-driven clustering based on neuroanatomical phenotypes may help to elucidate neurobiological associations BDII-D.Inflammatory cytokines, symptoms, features were assessed 150 BDII-D patients. Sixty-eight cortical surface area (SA) 19 subcortical volumes extracted using FreeSurfer. The ChP was segmented manually 3D Slicer. Regularized canonical correlation analysis used identify significantly correlated components SA (excluding the ChP), followed by k-means define brain-derived subgroups of BDII-D. Low-grade derived averaging standardized z scores interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), which computed create a composite z-value score. Partial Pearson correlations multiple comparison correction conducted explore volume.Subgroup I demonstrated smaller SA, higher compared with subgroup II. Greater associated low-grade (mean r = 0.289, q 0.003), CRP 0.249, 0.007), IL-6 (left 0.200, 0.03), TNF-α (right 0.226, 0.01), while greater IL-1β severe depressive (r 0.218, 0.045).Neuroanatomically-derived differed their levels volume. These findings suggest an important role elevated peripheral

Language: Английский

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Glymphatic dysfunction mediates the influence of choroid plexus enlargement on information processing speed in patients with white matter hyperintensities

Cerebral Cortex, Journal Year: 2024, Volume and Issue: 34(6)

Published: June 1, 2024

Abstract Glymphatic dysfunction has been correlated with cognitive decline, a higher choroid plexus volume (CPV) being linked to slower glymphatic clearance rate. Nevertheless, the interplay between CPV, function, and impairment in white matter hyperintensities (WMHs) not yet investigated. In this study, we performed neuropsychological assessment, T1-weighted three-dimensional (3D-T1) images, diffusion tensor imaging (DTI) cohort of 206 WMHs subjects 43 healthy controls (HCs) further explore relationship. The DTI analysis along perivascular space (DTI-ALPS) index, as measure was calculated based on DTI. Severe significantly worse information processing speed (IPS) than other three groups, well executive function HCs mild WMHs. Additionally, severe demonstrated lower DTI-ALPS index CPV Moderate displayed Mini-Mental State Examination, IPS, negatively but positively patients. partially mediated association indicating potential mechanism for WMHs-related impairment. may act valuable prognostic marker system promising therapeutic target

Language: Английский

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Toxoplasma gondii, endothelial cells and schizophrenia: is it just a barrier matter?

Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: April 10, 2025

Toxoplasma gondii is an obligatory intracellular parasite responsible for causing toxoplasmosis. It estimated that approximately one-third of the world's population has positive serology Acute T. infection often results in subtle symptoms because its nonspecific nature. Owing to immune pressure, parasites tend encyst and persist different tissues organs, such as brain, chronicling infection. While most chronically infected individuals do not develop significant symptoms, can affect central nervous system (CNS), leading range from dizziness behavioral changes. To reach CNS, must overcome blood-brain barrier, which composed primarily endothelial cells. these cells are typically efficient at separating blood elements infection, they only permit parasitic colonization CNS but also contribute inflammatory profile may exacerbate previously established conditions both local systemic levels. An increasing body research demonstrated a potential link between by cellular or humoral response with worsening psychiatric conditions, schizophrenia. Therefore, continually advancing aimed understanding mitigating relationship schizophrenia imperative.

Language: Английский

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Identification of neurodevelopmental organization of the cell populations of juvenile Huntington’s disease using dorso-ventral HD organoids and HD mouse embryos

Published: Jan. 8, 2025

Huntington’s disease (HD) is a polyglutamine neurodegenerative involving pathogenesis within the striatum and cerebral cortex neurodevelopmental component, particularly in juvenile HD form (JOHD). We established fused dorsal-ventral system, imitating interaction single organoid to discover impairments at level of cell populations. found range early pathogenic phenotypes indicating that brain development affected by impaired neurogenesis. The occurred already early-stage 60-day organoids humanized mouse embryos, time beginning neurogenesis choroid plexus development. demonstrated embryonic brains had gene expression profiles maturation neurons increased genes responsible for proliferation compared differentiation control organoids. By using scRNA-seq, population was highly abundant brains. Cortical populations co-expressed HTT function (mitotic spindle cilia). occurrence were mitigated our compensatory model, mosaic dorsal/ventral (D/V) or V/D HD/control Finally, we TTR protein, marker, elevated adult serum, may be promising marker detecting HD. In summary, dorso-ventral identify spectrum features, including delayed maturation. demonstrate characteristic aberrant neurodevelopment, contains which can translated as blood

Language: Английский

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