5 results on '"De Giorgio, F."'
Search Results
2. Dysregulation of FLVCR1a-dependent mitochondrial calcium handling in neural progenitors causes congenital hydrocephalus.
- Author
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Bertino F, Mukherjee D, Bonora M, Bagowski C, Nardelli J, Metani L, Zanin Venturini DI, Chianese D, Santander N, Salaroglio IC, Hentschel A, Quarta E, Genova T, McKinney AA, Allocco AL, Fiorito V, Petrillo S, Ammirata G, De Giorgio F, Dennis E, Allington G, Maier F, Shoukier M, Gloning KP, Munaron L, Mussano F, Salsano E, Pareyson D, di Rocco M, Altruda F, Panagiotakos G, Kahle KT, Gressens P, Riganti C, Pinton PP, Roos A, Arnold T, Tolosano E, and Chiabrando D
- Subjects
- Animals, Humans, Mice, Inositol 1,4,5-Trisphosphate Receptors metabolism, Inositol 1,4,5-Trisphosphate Receptors genetics, Neurogenesis genetics, Calcium metabolism, Hydrocephalus metabolism, Hydrocephalus genetics, Hydrocephalus pathology, Membrane Transport Proteins metabolism, Membrane Transport Proteins genetics, Mitochondria metabolism, Neural Stem Cells metabolism, Neural Stem Cells pathology, Receptors, Virus metabolism, Receptors, Virus genetics
- Abstract
Congenital hydrocephalus (CH), occurring in approximately 1/1,000 live births, represents an important clinical challenge due to the limited knowledge of underlying molecular mechanisms. The discovery of novel CH genes is thus essential to shed light on the intricate processes responsible for ventricular dilatation in CH. Here, we identify FLVCR1 (feline leukemia virus subgroup C receptor 1) as a gene responsible for a severe form of CH in humans and mice. Mechanistically, our data reveal that the full-length isoform encoded by the FLVCR1 gene, FLVCR1a, interacts with the IP3R3-VDAC complex located on mitochondria-associated membranes (MAMs) that controls mitochondrial calcium handling. Loss of Flvcr1a in mouse neural progenitor cells (NPCs) affects mitochondrial calcium levels and energy metabolism, leading to defective cortical neurogenesis and brain ventricle enlargement. These data point to defective NPCs calcium handling and metabolic activity as one of the pathogenetic mechanisms driving CH., Competing Interests: Declaration of interests E.T., V.F., D.Chiabrando, S.P., F.B., and A.L.A. are inventors in a patent filed by the University of Torino, not related to the research reported here., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
3. Sex-specific behavioural, metabolic, and immunohistochemical changes after repeated administration of the synthetic cannabinoid AKB48 in mice.
- Author
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Corli G, Roda E, Tirri M, Bilel S, De Luca F, Strano-Rossi S, Gaudio RM, De-Giorgio F, Fattore L, Locatelli CA, and Marti M
- Subjects
- Mice, Male, Female, Animals, Cannabinoid Receptor Agonists pharmacology, Receptors, Cannabinoid, Down-Regulation, Receptor, Cannabinoid, CB1, Cannabinoids pharmacology, Cannabis
- Abstract
Background and Purpose: AKB48 is a synthetic cannabinoid illegally sold for its psychoactive cannabis-like effects that have been associated with acute intoxication and whose effects are poorly known., Experimental Approach: Using a behavioural, neurochemical, and immunohistochemical approach, we investigated the pharmaco-toxicological effects, pharmacokinetics, and neuroplasticity at cannabinoid CB
1 receptors in the cerebellum and cortex induced by repeated AKB48 administration in male and female mice., Key Results: The effects of AKB48 varied significantly depending on sex and treatment duration. The first injection impaired sensorimotor responses and reduced body temperature, analgesia, and breath rate to a greater extent in females than in males; the second injection induced stronger effects in males while the third injection of AKB48 induced weaker responses in both sexes, suggesting emergence of tolerance. The CB1 receptor antagonist NESS-0327 prevented the effects induced by repeated AKB48, confirming a CB1 receptor-mediated action. Blood AKB48 levels were higher in females than in males and repeated administration caused a progressive rise of AKB48 levels in both sexes, suggesting an inhibitory effect on cytochrome activity. Finally, immunohistochemical analysis revealed higher expression of CB1 receptors in the cerebellum and cortex of females, and a rapid CB1 receptor down-regulation in cerebellar and cortical areas following repeated AKB48 injections, with neuroadaptation occurring generally more rapidly in females than in males., Conclusion and Implications: We have shown for the first time that AKB48 effects significantly vary with prolonged use and that sex affects the pharmacodynamic/pharmacokinetic responses to repeated administration, suggesting a sex-tailored approach in managing AKB48-induced intoxication., (© 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)- Published
- 2024
- Full Text
- View/download PDF
4. Immunohistochemical expression of HMGB1 and related proteins in the skin as a possible tool for determining post-mortem interval: a preclinical study.
- Author
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De-Giorgio F, Bergamin E, Baldi A, Gatta R, and Pascali VL
- Subjects
- Male, Mice, Animals, Beclin-1, Autopsy, Time, Postmortem Changes, HMGB1 Protein metabolism
- Abstract
Determining the post-mortem interval (PMI) is one of forensic pathology's primary objectives and one of its most challenging tasks. Numerous studies have demonstrated the accuracy of histomorphology and immunohistochemical investigations in determining the time of death. Nevertheless, the skin, a robust and easy-to-remove tissue, has only been partially analyzed so far. By studying 20 adult male mice, we tried to determine whether post-mortem immunohistochemical detection in the skin of HMGB1 proteins and associated components (Beclin1 and RAGE) could be used for this purpose. We discovered that nuclear HMGB1 overexpression indicates that death occurred within the previous 12 h, nuclear HMGB1 negativization with high cytoplasmic HMGB1 intensity indicates that death occurred between 12 and 36 h earlier and cytoplasmic HMGB1 negativization indicates that more than 48 h have passed since death. RAGE and Beclin1 levels in the cytoplasm also decreased with time. The latter proteins' negativization might indicate that more than 24 and 36 h, respectively, have passed from the time of death. These indicators might potentially be helpful in forensic practice for determining the PMI using immunohistochemistry., (© 2023. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
5. FLVCR1a Controls Cellular Cholesterol Levels through the Regulation of Heme Biosynthesis and Tricarboxylic Acid Cycle Flux in Endothelial Cells.
- Author
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Manco M, Ammirata G, Petrillo S, De Giorgio F, Fontana S, Riganti C, Provero P, Fagoonee S, Altruda F, and Tolosano E
- Subjects
- Mice, Animals, Membrane Transport Proteins metabolism, Cell Membrane metabolism, Mice, Knockout, Heme metabolism, Endothelial Cells metabolism, Citric Acid Cycle
- Abstract
Feline leukemia virus C receptor 1a (FLVCR1a), initially identified as a retroviral receptor and localized on the plasma membrane, has emerged as a crucial regulator of heme homeostasis. Functioning as a positive regulator of δ-aminolevulinic acid synthase 1 (ALAS1), the rate-limiting enzyme in the heme biosynthetic pathway, FLVCR1a influences TCA cycle cataplerosis, thus impacting TCA flux and interconnected metabolic pathways. This study reveals an unexplored link between FLVCR1a, heme synthesis, and cholesterol production in endothelial cells. Using cellular models with manipulated FLVCR1a expression and inducible endothelial-specific Flvcr1a -null mice, we demonstrate that FLVCR1a-mediated control of heme synthesis regulates citrate availability for cholesterol synthesis, thereby influencing cellular cholesterol levels. Moreover, alterations in FLVCR1a expression affect membrane cholesterol content and fluidity, supporting a role for FLVCR1a in the intricate regulation of processes crucial for vascular development and endothelial function. Our results underscore FLVCR1a as a positive regulator of heme synthesis, emphasizing its integration with metabolic pathways involved in cellular energy metabolism. Furthermore, this study suggests that the dysregulation of heme metabolism may have implications for modulating lipid metabolism. We discuss these findings in the context of FLVCR1a's potential heme-independent function as a choline importer, introducing additional complexity to the interplay between heme and lipid metabolism.
- Published
- 2024
- Full Text
- View/download PDF
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