Lipid markers and related transcripts during excitotoxic neurodegeneration in kainate-treated mice.
Eur J Neurosci
; 50(1): 1759-1778, 2019 07.
Article
en En
| MEDLINE
| ID: mdl-30767299
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Microglía
/
Perfilación de la Expresión Génica
/
Región CA1 Hipocampal
/
Gotas Lipídicas
/
Ácido Kaínico
/
Lípidos de la Membrana
/
Degeneración Nerviosa
/
Neuronas
Límite:
Animals
Idioma:
En
Revista:
Eur J Neurosci
Asunto de la revista:
NEUROLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Francia