Age-Related Cerebral Ventriculomegaly occurs in Patients with Primary Ciliary Dyskinesia DOI Creative Commons

Franziska Eisenhuth,

Joy E. Agbonze,

Adam M.R. Groh

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 15, 2024

Abstract Primary ciliary dyskinesia (PCD) is a genetic disorder causing motile dysfunction primarily affecting the respiratory and reproductive systems. However, impact of PCD on central nervous system, through cilia in multiciliated ependymal cells, remains poorly understood. We hypothesized that patients with exhibit sub-clinical ventriculomegaly due to dysfunction, which may influence neuropsychiatric diagnoses. demonstrated highly specific expression levels known PCD-related genes human brain cells ( p <0.0001), supporting their potential role regulating function. Computed tomography sinus images from n =33) age/sex-matched controls =64) were analysed. Patients displayed significantly larger ventricular areas <0.0001) Evans index <0.01), indicating was consistent across all subgroups. Ventricular enlargement correlated positively increasing age compared <0.001). Chart review high prevalence (39%) neuropsychiatric/neurological disorders adult did not correlate degree ventriculomegaly. Our findings suggest have unrecognized, mild potentially correlates ageing. Further study required determine if contributes or other morbidity PCD.

Language: Английский

Paediatric hydrocephalus DOI
Kristopher T. Kahle, Petra M. Klinge, Jenna E. Koschnitzky

et al.

Nature Reviews Disease Primers, Journal Year: 2024, Volume and Issue: 10(1)

Published: May 16, 2024

Language: Английский

Citations

17
Neuroprotective effects of gemfibrozil in neurological disorders: Focus on inflammation and molecular mechanisms DOI Creative Commons
Mehraveh Sadeghi Ivraghi, Mohammad Yasin Zamanian, Reena Gupta

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 30(3)

Published: Oct. 30, 2023

Abstract Background Gemfibrozil (Gem) is a drug that has been shown to activate PPAR‐α, nuclear receptor plays key role in regulating lipid metabolism. Gem used lower the levels of triglycerides and reduce risk coronary heart disease patients. Experimental studies vitro vivo have can prevent or slow progression neurological disorders (NDs), including cerebral ischemia (CI), Alzheimer's (AD), Parkinson's (PD), multiple sclerosis (MS). Neuroinflammation known play significant these disorders. Method The literature review for this study was conducted by searching Scopus, Science Direct, PubMed, Google Scholar databases. Result results show neuroprotective effects through several cellular molecular mechanisms such as: (1) ability upregulate pro‐survival factors (PGC‐1α TFAM), promoting survival function mitochondria brain, (2) strongly inhibits activation NF‐κB, AP‐1, C/EBPβ cytokine‐stimulated astroglial cells, which are increase expression iNOS production NO response proinflammatory cytokines, (3) protects dopamine neurons MPTP mouse model PD increasing PPARα, turn stimulates GDNF astrocytes, (4) reduces amyloid plaque pathology, activity glial improves memory, (5) increases myelin genes (MBP CNPase) via PPAR‐β, (6) hippocampal BDNF counteract depression. Conclusion According study, investigated its potential therapeutic effect NDs. Further research needed fully understand

Language: Английский

Citations

17
Multiciliated ependymal cells: an update on biology and pathology in the adult brain DOI
Adam M.R. Groh,

Yeji Lori Song,

Fiona Tea

et al.

Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 148(1)

Published: Sept. 10, 2024

Language: Английский

Citations

8
Conditioned medium-enriched umbilical cord mesenchymal stem cells: a potential therapeutic strategy for spinal cord injury, unveiling transcriptomic and secretomic insights DOI
Rajasekaran Subbarayan, Murugan Dinesh, S. Thirupathi Kumara Raja

et al.

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)

Published: April 24, 2024

Language: Английский

Citations

7
Congenital hydrocephalus: a review of recent advances in genetic etiology and molecular mechanisms DOI Creative Commons
Xiuyun Liu,

Xin Song,

Marek Czosnyka

et al.

Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)

Published: Aug. 12, 2024

Abstract The global prevalence rate for congenital hydrocephalus (CH) is approximately one out of every five hundred births with multifaceted predisposing factors at play. Genetic influences stand as a major contributor to CH pathogenesis, and epidemiological evidence suggests their involvement in up 40% all cases observed globally. Knowledge about an individual’s genetic susceptibility can significantly improve prognostic precision while aiding clinical decision-making processes. However, the precise etiology has only been pinpointed fewer than 5% human instances. More occurrences are required comprehensive gene sequencing aimed uncovering additional potential loci. A deeper comprehension its underlying genetics may offer invaluable insights into molecular cellular basis this brain disorder. This review provides summary pertinent genes identified through technologies humans, addition 4 currently associated (two X-linked L1CAM AP1S2 , two autosomal recessive MPDZ CCDC88C ). Others predominantly participate aqueduct abnormalities, ciliary movement, nervous system development. prospective CH-related revealed animal model gene-editing techniques further outlined, focusing mainly on pathways, namely cilia synthesis ion channels transportation, Reissner’s fiber (RF) synthesis, cell apoptosis, neurogenesis. Notably, proper functioning motile significant impulsion cerebrospinal fluid (CSF) circulation within ventricles mutations cilia-related constitute primary cause condition. So far, limited number CH-associated have humans. integration genotype phenotype disease diagnosis represents new trend medical field. Animal models provide pathogenesis contribute our understanding association related complications, such renal cysts, scoliosis, cardiomyopathy, these also play role development diseases. Genes discovered animals present targets treatments but require validation future studies.

Language: Английский

Citations

6
Ependymal cells: roles in central nervous system infections and therapeutic application DOI Creative Commons
Shiqi Xie, Feng Li

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Oct. 9, 2024

Ependymal cells are arranged along the inner surfaces of ventricles and central canal spinal cord, providing anatomical, physiological immunological barriers that maintain cerebrospinal fluid (CSF) homeostasis. Based on this, studies have found alterations in gene expression, cell junctions, cytokine secretion metabolic disturbances can lead to dysfunction ependymal cells, thereby participating onset progression nervous system (CNS) infections. Additionally, exhibit proliferative regenerative potential as well secretory functions during CNS injury, contributing neuroprotection post-injury recovery. Currently, primarily focus basic investigations their morphology, function expression; however, there is a notable lack clinical translational examining molecular mechanisms by which involved disease progression. This limits our understanding infections development therapeutic applications. Therefore, this review will discuss mechanism underlying involvement infections, explore for application treatment modalities.

Language: Английский

Citations

5
The IgCAM BT-IgSF (IgSF11) Is Essential for Connexin43-Mediated Astrocyte–Astrocyte Coupling in Mice DOI Creative Commons

Laura Pelz,

Laura Dossou,

Nine Kompier

et al.

eNeuro, Journal Year: 2024, Volume and Issue: 11(3), P. ENEURO.0283 - 23.2024

Published: Feb. 22, 2024

The type I transmembrane protein BT-IgSF is predominantly localized in the brain and testes. It belongs to coxsackievirus adenovirus receptor subgroup of Ig cell adhesion proteins, which are hypothesized regulate connexin expression or localization. Here, we studied putative link between connexins astrocytes, ependymal cells, neurons mouse. Global knock-out caused an increase clustering connexin43 (Gja1), but not connexin30 (Gjb6), on astrocytes cells. Additionally, animals displayed reduced levels cortex hippocampus. Importantly, analysis biocytin spread hippocampal cortical slices from mature mice either sex revealed a decrease astrocytic cell–cell coupling absence BT-IgSF. Blocking biosynthesis proteolysis showed that lysosomal pathway increased degradation astrocytes. Localization subcellular compartments was impaired mutants. In contrast connexin43, localization connexin36 (Gjd2) were affected by Overall, our data indicate IgCAM essential for correct gap junction–mediated astrocyte–astrocyte communication.

Language: Английский

Citations

4
Characterizing progenitor cells in developing and injured spinal cord: Insights from single-nucleus transcriptomics and lineage tracing DOI Creative Commons
Qi Zhang, Xianming Wu,

Yongheng Fan

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(2)

Published: Jan. 6, 2025

Various mature tissue-resident cells exhibit progenitor characteristics following injury. However, the existence of endogenous stem with multiple lineage potentials in adult spinal cord remains a compelling area research. In this study, we present cross-species investigation that extends from development to We used single-nucleus transcriptomic sequencing and genetic tracing characterize neural cord. Our findings show ciliated ependymal lose gene signatures proliferation ability differentiation NPCs within ventricular zone. By combining transcriptome datasets rhesus macaque injury (SCI) model developmental human datasets, revealed respond minimally cannot revert state. Intriguingly, observed astrocytes transdifferentiating into oligodendrocytes postinjury through experiments. Further analysis identifies an intermediate-state glial cell population expressing both astrocyte oligodendrocyte feature genes cords. The transition ratio increased after remodeling microenvironment by functional scaffolds. Overall, our results highlight remarkable multilineage potential

Language: Английский

Citations

0
Role of Glial Cells and Receptors in Schizophrenia Pathogenesis DOI
Yousef Tizabi, Marta C. Antonelli,

Daniela Tizabi

et al.

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(2)

Published: Jan. 27, 2025

Language: Английский

Citations

0
YAP/TAZ-associated cell signaling – at the crossroads of cancer and neurodevelopmental disorders DOI Creative Commons

Aderonke O. Ajongbolo,

Sigrid A. Langhans

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 28, 2025

YAP/TAZ (Yes-associated protein/paralog transcriptional co-activator with PDZ-binding domain) are cofactors that the key and major downstream effectors of Hippo signaling pathway. Both known to play a crucial role in defining cellular outcomes, including cell differentiation, proliferation, apoptosis. Aside from canonical cascade components MST1/2 (mammalian STE20-like kinase 1/2), SAV1 (Salvador homologue 1), MOB1A/B (Mps one binder activator 1A/B) LATS1/2 (large tumor suppressor 1/2) upstream YAP/TAZ, activation is also influenced by numerous other pathways. Such non-canonical regulation includes well-known growth factor pathways such as epidermal receptor (EGFR)/ErbB family, Notch, Wnt well cell-cell adhesion, cell-matrix interactions mechanical cues cell’s microenvironment. This puts at center complex network capable regulating developmental processes tissue regeneration. On hand, dysregulation has been implicated diseases various cancers neurodevelopmental disorders. Indeed, recent years, parallels between cancer development disorders have become apparent being these review discusses brain development, special focus on interconnection different conditions.

Language: Английский

Citations

0