Astrocyte alterations during Osmotic Demyelination Syndrome: intermediate filaments, aggresomes, proteasomes, and glycogen storages

Ultrastructural Pathology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 46

Published: March 10, 2025

A murine model mimicking the human osmotic demyelination syndrome (ODS) revealed with histology demyelinated alterations in relay posterolateral (VPL) and ventral posteromedial (VPM) thalamic nuclei 12 h 48 after chronic hyponatremia due to a fast reinstatement of osmolality. Abnormal expression astrocyte markers ALDHL1 GFAP immunohistochemistry these ODS altered zones, prompted aims verify both protoplasmic fibrillar astrocytes ultrastructure those changes other associated subcellular modifications. This investigation included four groups mice: Sham (NN; n = 13), hyponatremic (HN; 11), sacrificed restoration normal natremia (ODS12h; 6), mice afterward, or ODS48 (n 9). Out mice, LM microscopy, zones NN 2), HN ODS12h 3) ODS48h samples. There, comparisons between organelles, GFAP, glycogen content changes. Thalamic epicenter damages comprised (PA) (FA) necroses along neuropil destructions neuron Wallerian injuries surrounded by centrifugal region gradient revealing worse mild destructions. Ultrastructure aspects resilient PAs disclosed mitochondria accumulations beta- alpha-glycogen granules that became eventually captured into phagophores as glycophagosomes ODS48h. time lapse FAs accumulated ribonucleoproteins, cytoskeletal aggresomes, proteasomes but distant maintained fibrils typical dispersed β-glycogen, including their surroundings. Thus, triggered involved post-transcriptional post-translational modifications such were unable use metabolites own defects while stalled aggresomes ablation. Resilient restitution amphibolism where carbohydrate storages tripartite extensions supply for restored nerve axon initial segments, neural Ranvier's junctions, oligodendrocyte -neuron junctional contacts. caused damage adjacent destruction regional loss dispatched energetic metabolic exchanges within injured region, bearing proportional collateral injuries, which reactive repairs rebalanced osmolarity.

Language: Английский

---

Neuroadaptation in neurodegenerative diseases: compensatory mechanisms and therapeutic approaches

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2025, Volume and Issue: 139, P. 111375 - 111375

Published: April 23, 2025

Language: Английский

---

Glutathione Metabolism of the Brain—The Role of Astrocytes

Journal of Neurochemistry, Journal Year: 2025, Volume and Issue: 169(5)

Published: May 1, 2025

ABSTRACT Astrocytes have essential functions in the brain as partners of neurons many metabolic and homeostatic processes. The metabolism tripeptide GSH (γ‐L‐glutamyl‐L‐cysteinyl‐glycine) is an important example a interaction between astrocytes neurons. present cells millimolar concentrations has antioxidant substrate for detoxification reactions. A high content protects against oxidative stress toxins therefore beneficial astrocytic self‐defense that helps to maintain will enable eliminate potential before they may reach other cells. In addition, provide with amino acids required synthesis process involves export from by multidrug resistance protein 1, extracellular processing via γ‐glutamyl transpeptidase generate dipeptide cysteinyl‐glycine, cleavage this neuronal ectopeptidase aminopeptidase N. As strongly depends on cytosolic concentration, also facilitate release thereby supply precursors neighboring article, we give overview current knowledge astrocytes, address how can help functions, discuss open questions future perspectives research healthy diseased brain. image

Language: Английский

---