Ezetimibe Enhances Lipid Droplet and Mitochondria Contact Formation, Improving Fatty Acid Transfer and Reducing Lipotoxicity in Alport Syndrome Podocytes.

Mitochondrial dysfunction is a critical factor in the pathogenesis of Alport syndrome (AS), contributing to podocyte injury and disease progression. Ezetimibe, a lipid-lowering drug, is known to inhibit cholesterol and fatty acid uptake and to reduce triglyceride content in the kidney cortex of mice with AS. However, its effects on lipid droplet (LD) utilization by mitochondria have not been explored.

Birefringence in Injection-Molded Cyclic Olefin Copolymer Substrates and Its Impact on Integrated Photonic Structures.

This contribution quantifies the birefringence within injection-molded cyclic olefin copolymer plates and discusses its impact on the mechanical properties of the plates. It also focuses on the impact of birefringence on integrated waveguides and Bragg gratings and provides fabrication guidelines for such structures. The anisotropy in all three dimensions of the workpiece is examined by means of polarimetry and a prism coupler.

Inward Operation of Sodium-Bicarbonate Cotransporter 1 Promotes Astrocytic Na Loading and Loss of ATP in Mouse Neocortex during Brief Chemical Ischemia.

Ischemic conditions cause an increase in the sodium concentration of astrocytes, driving the breakdown of ionic homeostasis and exacerbating cellular damage. Astrocytes express high levels of the electrogenic sodium-bicarbonate cotransporter1 (NBCe1), which couples intracellular Na homeostasis to regulation of pH and operates close to its reversal potential under physiological conditions. Here, we analyzed its mode of operation during transient energy deprivation via imaging astrocytic pH, Na, and ATP in organotypic slice cultures of the mouse neocortex, complemented with patch-clamp and ion-selective microelectrode recordings and computational modeling.

Activation of TRPV4 channels promotes the loss of cellular ATP in organotypic slices of the mouse neocortex exposed to chemical ischemia.

The vertebrate brain has an exceptionally high energy need. During ischemia, intracellular ATP concentrations decline rapidly, resulting in the breakdown of ion gradients and cellular damage. Here, we employed the nanosensor ATeam1.

Modeling the heterogeneity of sodium and calcium homeostasis between cortical and hippocampal astrocytes and its impact on bioenergetics.

Emerging evidence indicates that neuronal activity-evoked changes in sodium concentration in astrocytes Na represent a special form of excitability, which is tightly linked to all other major ions in the astrocyte and extracellular space, as well as to bioenergetics, neurotransmitter uptake, and neurovascular coupling. Recently, one of us reported that Na transients in the neocortex have a significantly higher amplitude than those in the hippocampus. Based on the extensive data from that study, here we develop a detailed biophysical model to further understand the origin of this heterogeneity and how it affects bioenergetics in the astrocytes.