Astrocyte lipocalin-2 modestly effects disease severity in a mouse model of multiple sclerosis while reducing mature oligodendrocyte protein and mRNA expression

Neurosci Lett. 2023 Oct 15:815:137497. doi: 10.1016/j.neulet.2023.137497. Epub 2023 Sep 23.

Abstract

Roles for lipocalin-2 (LCN2, also referred to as neutrophil gelatinase associated lipocalin, NGAL) in the progression of disease in multiple sclerosis and its animal models have been reported; however, the importance of astrocyte-derived LCN2, a major source of LCN2, have not been defined. We found that clinical scores in experimental autoimmune encephalomyelitis (EAE) were modestly delayed in mice with conditional knockout of LCN2 from astrocytes, associated with a small decrease in astrocyte GFAP expression. Immunostaining and qPCR of spinal cord samples showed decreased oligodendrocyte proteolipid protein and transcription factor Olig2 expression, but no changes in PDGFRα expression. These results suggest astrocyte LCN2 contributes to early events in EAE and reduces damage to mature oligodendrocytes at later times.

Keywords: Astrocyte; EAE; LCN2; Lipocalin; Multiple Sclerosis; NGAL; Oligodendrocyte.

MeSH terms

  • Acute-Phase Proteins / genetics
  • Acute-Phase Proteins / metabolism
  • Animals
  • Astrocytes / metabolism
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental* / metabolism
  • Lipocalin-2 / genetics
  • Lipocalin-2 / metabolism
  • Lipocalins / genetics
  • Lipocalins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis* / metabolism
  • Oligodendroglia / metabolism
  • RNA, Messenger / metabolism

Substances

  • Lipocalin-2
  • Acute-Phase Proteins
  • Lipocalins
  • RNA, Messenger