Lipocalin 2 as a Putative Modulator of Local Inflammatory Processes in the Spinal Cord and Component of Organ Cross talk After Spinal Cord Injury

Mol Neurobiol. 2021 Nov;58(11):5907-5919. doi: 10.1007/s12035-021-02530-7. Epub 2021 Aug 21.

Abstract

Lipocalin 2 (LCN2), an immunomodulator, regulates various cellular processes such as iron transport and defense against bacterial infection. Under pathological conditions, LCN2 promotes neuroinflammation via the recruitment and activation of immune cells and glia, particularly microglia and astrocytes. Although it seems to have a negative influence on the functional outcome in spinal cord injury (SCI), the extent of its involvement in SCI and the underlying mechanisms are not yet fully known. In this study, using a SCI contusion mouse model, we first investigated the expression pattern of Lcn2 in different parts of the CNS (spinal cord and brain) and in the liver and its concentration in blood serum. Interestingly, we could note a significant increase in LCN2 throughout the whole spinal cord, in the brain, liver, and blood serum. This demonstrates the diversity of its possible sites of action in SCI. Furthermore, genetic deficiency of Lcn2 (Lcn2-/-) significantly reduced certain aspects of gliosis in the SCI-mice. Taken together, our studies provide first valuable hints, suggesting that LCN2 is involved in the local and systemic effects post SCI, and might modulate the impairment of different peripheral organs after injury.

Keywords: Astroglia; Lipocalin 2; Organ cross talk; Spinal cord.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Astrocytes / metabolism
  • Brain / metabolism
  • Gene Expression Regulation
  • Gliosis / metabolism
  • Lipocalin-2 / blood
  • Lipocalin-2 / deficiency
  • Lipocalin-2 / genetics
  • Lipocalin-2 / physiology*
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / metabolism
  • Neuroinflammatory Diseases / metabolism*
  • Organ Specificity
  • Paraplegia / etiology
  • Paraplegia / physiopathology
  • RNA, Messenger / biosynthesis
  • Spinal Cord / metabolism*
  • Spinal Cord Injuries / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • Lipocalin-2
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Lcn2 protein, mouse