Enhanced autophagy contributes to excitotoxic lesions in a rat model of preterm brain injury

Cell Death & Disease
Céline DesclouxJulien Puyal

Abstract

Cystic periventricular leukomalacia is commonly diagnosed in premature infants, resulting from severe hypoxic-ischemic white matter injury, and also involving some grey matter damage. Very few is known concerning the cell death pathways involved in these types of premature cerebral lesions. Excitotoxicity is a predominant mechanism of hypoxic-ischemic injury in the developing brain. Concomitantly, it has been recently shown that autophagy could be enhanced in excitotoxic conditions switching this physiological intracellular degradation system to a deleterious process. We here investigated the role of autophagy in a validated rodent model of preterm excitotoxic brain damage mimicking in some aspects cystic periventricular leukomalacia. An excitotoxic lesion affecting periventricular white and grey matter was induced by injecting ibotenate, a glutamate analogue, in the subcortical white matter (subcingulum area) of five-day old rat pups. Ibotenate enhanced autophagy in rat brain dying neurons at 24 h as shown by increased presence of autophagosomes (increased LC3-II and LC3-positive dots) and enhanced autophagic degradation (SQSTM1 reduction and increased number and size of lysosomes (LAMP1- and CATHEPSIN B-positive vesicles)). C...Continue Reading

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Citations

May 27, 2020·Journal of Neural Transmission·Elena PompiliFrancesco Fornai
May 10, 2019·Frontiers in Physiology·Silvia PregnolatoKaren Luyt
Nov 22, 2019·Frontiers in Cellular Neuroscience·Lei XiaChanglian Zhu
Mar 7, 2020·Frontiers in Cell and Developmental Biology·Anita C TruttmannJulien Puyal
Dec 29, 2019·International Journal of Molecular Sciences·Sabrina CeccarigliaCarlo Gangitano
Jan 9, 2021·Journal of Neuroscience Research·Rongjiao ShaoDerong Cui
Jul 24, 2021·The Journal of Biological Chemistry·Skylar E DavisAndrew E Arrant

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Methods Mentioned

BETA
electron microscopy
transfection
Infrared Imaging

Software Mentioned

Zen Blue
ImageJ
Adobe Photoshop
Zeiss
LSM
GraphPad PRISM

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