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Eur J Neurosci. 2019 Jul;50(1):1759-1778. doi: 10.1111/ejn.14375. Epub 2019 Mar 25.

Lipid markers and related transcripts during excitotoxic neurodegeneration in kainate-treated mice.

Author information

1
Inserm U1127, CNRS UMR7225, Sorbonne Université, UPMC Université Paris 6 UMR S1127, Institut du Cerveau et de la Moelle Epinière, CHU Pitié-Salpêtrière, Paris, France.
2
Institut de Biologie de l'École normale supérieure (IBENS), École Normale Supérieure, CNRS, INSERM PSL Université Paris, Paris, France.

Abstract

Lipid homeostasis is dysregulated in some neurodegenerative diseases and after brain injuries due to excess glutamate or lack of oxygen. However the kinetics and cell specificity of dysregulation in different groups of lipids during excitotoxic neuronal death are not clear. Here we examined the changes during excitotoxic neuronal death induced by injecting kainic acid (KA) into the CA1 region of mouse hippocampus. We compared neuronal loss and glial cell proliferation with changes in lipid-related transcripts and markers for different lipid groups, over 12 days after KA-treatment. As neurons showed initial signs of damage, transcripts and proteins linked to fatty acid oxidation were up-regulated. Cholesterol biosynthesis induced by transcripts controlled by the transcription factor Srebp2 seems to be responsible for a transient increase in neuronal free cholesterol at 1 to 2 days. In microglia, but not in neurons, Perilipin-2 associated lipid droplets were induced and properties of Nile red emissions suggest lipid contents change over time. After microglial expression of phagocytotic markers at 2 days, some neutral lipid deposits co-localized with lysosome markers of microglia and were detected within putative phagocytotic cups. These data delineate distinct lipid signals in neurons and glial cells during excitotoxic processes from initial neuronal damage to engagement of the lysosome-phagosome system.

KEYWORDS:

cholesterol; fatty acids; hippocampus; lipid droplets; microglia; neurons

PMID:
30767299
DOI:
10.1111/ejn.14375

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