Synergistic label-free fluorescence imaging and miRNA studies reveal dynamic human neuron-glial metabolic interactions following injury.

Autor: Zhang Y; Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA., Savvidou M; Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA., Liaudanskaya V; Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA., Singh P; Data Intensive Studies Center, Tufts University, Medford, MA 02155, USA., Fu Y; Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA.; Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA., Nasreen A; Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA., Coe M; Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA., Kelly M; Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA., Snapper D; Department of Pharmacology and Molecular Therapeutics, Uniformed Services University, Bethesda, MD 20814, USA., Wagner C; School of Nursing, Johns Hopkins University, 525 N. Wolfe Street, Baltimore, MD 21205, USA., Gill J; School of Nursing, Johns Hopkins University, 525 N. Wolfe Street, Baltimore, MD 21205, USA.; Department of Neurology, School of Medicine, Johns Hopkins University, 525 N. Wolfe Street, Baltimore, MD 21205, USA., Symes A; Department of Pharmacology and Molecular Therapeutics, Uniformed Services University, Bethesda, MD 20814, USA., Patra A; Data Intensive Studies Center, Tufts University, Medford, MA 02155, USA., Kaplan DL; Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA., Beheshti A; McGowan Institute for Regenerative Medicine - Center for Space Biomedicine, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Georgakoudi I; Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA.; Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.; Program in Cell, Molecular, and Developmental Biology, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111, USA.; Dartmouth Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon NH 03766, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2024 Dec 13; Vol. 10 (50), pp. eadp1980. Date of Electronic Publication: 2024 Dec 11.
DOI: 10.1126/sciadv.adp1980
Abstrakt: Neuron-glial cell interactions following traumatic brain injury (TBI) determine the propagation of damage and long-term neurodegeneration. Spatiotemporally heterogeneous cytosolic and mitochondrial metabolic pathways are involved, leading to challenges in developing effective diagnostics and treatments. An engineered three-dimensional brain tissue model comprising human neurons, astrocytes, and microglia is used in combination with label-free, two-photon imaging and microRNA studies to characterize metabolic interactions between glial and neuronal cells over 72 hours following impact injury. We interpret multiparametric, quantitative, optical metabolic assessments in the context of microRNA gene set analysis and identify distinct metabolic changes in neurons and glial cells. Glycolysis, nicotinamide adenine dinucleotide phosphate (reduced form) and glutathione synthesis, fatty acid synthesis, and oxidation are mobilized within glial cells to mitigate the impacts of initial enhancements in oxidative phosphorylation and fatty acid oxidation within neurons, which lack robust antioxidant defenses. This platform enables enhanced understanding of mechanisms that may be targeted to improve TBI diagnosis and treatment.
Databáze: MEDLINE