Fañanas cells (FCs) are cerebellar glia of unknown function. First described more than a century ago, they have been almost absent from the scientific literature ever since. Here, we combined whole-cell, patch clamp recordings, near-UV laser photolysis, dye-loading and confocal imaging for a first characterization of FCs in terms of their morphology, electrophysiology and glutamate-evoked currents. We identified FCs of the molecular layer in cerebellar slices by their stubby process and small cell bodies. Despite their more compact shape compared to Bergmann glia (BGs), FCs showed similar membrane resistances and basal currents, suggesting that these passive currents are partly a result of electrical coupling between neighbouring glia. Dye filling and pharmacological experiments confirmed both homo- and heterotypic gap-junction coupling among FCs and BGs. Parallel-fibre stimulation evoked TTX-sensitive slow inward currents in FCs that were partially blocked by NBQX but not APV. Occasionally, we observed superimposed fast (milliseconds) current transients. Near-UV flash photolysis of MNI-caged glutamate revealed rapid desensitization of these AMPA-receptor mediated currents, which fully recovered only for stimulation intervals >500 ms. We mapped the highest current densities in proximal processes. We conclude that FCs respond with fast AMPA currents to local glutamate release and they integrate ambient glutamate rises to a slow inward current. Interestingly, we found FCs to prevail throughout adulthood at stable but different densities among cerebellar lobules, with the highest cell densities in lobules I-II and X. Our results strongly suggest that FCs are not just displaced BGs, and that they may have lobule-specific functions - both locally and at the circuit level, yet to be uncovered. KEY POINTS: Using whole-cell recordings and near-UV laser photolyisis of caged glutamate, we provide a first characterization of cells of Fañanas (FCs) in mouse cerebellar slices. FCs are present from postnatal day 5 onward throughout adulthood and have a lobule- dependent density. Parallel-fibre stimulation generates biphasic, predominantly AMPA-mediated currents in FCs. Currents induced in FCs by parallel fibre stimulation are not NMDA receptor-dependent and are enhanced upon glutamate-transporter block with TBOA. Local near-UV glutamate uncaging indicates that FCs can detect fast glutamatergic inputs on the millisecond-time scale. FCs functionally integrate into the glial syncytium.
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Int J Biol Macromol
January 2025
Departamento de Química Física, Facultade de Ciencias, Campus Terra, Universidade de Santiago de Compostela, 27002 Lugo, Spain. Electronic address:
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-beta (Aβ) aggregation, primarily involving the peptides Aβ40 and Aβ42. Human serum albumin (HSA) has emerged as a potential therapeutic agent due to its ability to bind Aβ, inhibit aggregation, and promote disaggregation. This study quantitatively examined the interactions of HSA with both monomeric and aggregated forms of Aβ40 and Aβ42 using fluorescence techniques, including bulk steady-state fluorescence, fluorescence anisotropy, time-resolved fluorescence, and Fluorescence Correlation Spectroscopy (FCS).
View Article and Find Full Text PDFBiomed Mater
January 2025
Physics and Applied Mathematics, Pakistan Institute of Engineering and applied Sciences, P.O. Box Nilore, Islamabad., Islamabad, Islamabad, 44000, PAKISTAN.
Ficus Carica extract (FC) is a natural herb that has received a lot of interest in cancer treatment due to its potential anticancer activities against various malignancies. However, due to FC's low bioavailability and low solubility, its clinical use as an anti-cancer medicine is constrained. The current study aimed to prepare FC-loaded PLGA nanoparticles (NPs) for cancer treatment.
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November 2024
Center for Artificial Intelligence Research, Wake Forest University School of Medicine, Winston-Salem, NC 27101, United States.
Pathway analysis plays a critical role in bioinformatics, enabling researchers to identify biological pathways associated with various conditions by analyzing gene expression data. However, the rise of large, multi-center datasets has highlighted limitations in traditional methods like Over-Representation Analysis (ORA) and Functional Class Scoring (FCS), which struggle with low signal-to-noise ratios (SNR) and large sample sizes. To tackle these challenges, we use a deep learning-based classification method, Gene PointNet, and a novel $P$-value computation approach leveraging the confusion matrix to address pathway analysis tasks.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
Department of Orthopaedics, Shanghai Jing'an District Zhabei Central Hospital, Shanghai 200070 China. Electronic address:
Background And Objectives: Intervertebral disc degeneration (IVDD) is a complex condition that necessitates the development of novel therapeutic strategies. The objective of this study was to investigate the therapeutic potential of Fuzi decoction (FZD) in the treatment of IVDD by examining its bioactive components, target genes, molecular interactions, pathways, and therapeutic efficacy.
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Genet Med
January 2025
Lipids and Atherosclerosis Laboratory, Department of Medicine and Dermatology, Centro de Investigaciones Médico Sanitarias (CIMES), Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA -Plataforma Bionand), University of Málaga, Málaga, Spain; Lipid Unit. Internal Medicine Service. University Hospital Virgen de la Victoria, Málaga, Spain.
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