Elsevier

Neuroscience Letters

Volume 412, Issue 1, 22 January 2007, Pages 73-77
Neuroscience Letters

Distribution and cellular localization of high mobility group box protein 1 (HMGB1) in the spinal cord of a transgenic mouse model of ALS

https://doi.org/10.1016/j.neulet.2006.10.063Get rights and content

Abstract

Although the aetiology of amyotrophic lateral sclerosis (ALS) is still elusive, increased attention has been put forward on events related to neuroinflammation and an active participation of glial cells in the ALS pathogenesis has been suggested. However, the specific role of many proinflammatory mediators that usually accompany the inflammatory changes is still largely unknown. High mobility group box protein 1 (HMGB1) is an ubiquitous nuclear protein that exerts numerous extranuclear and extracellular functions, including a proinflammatory activity, able to induce cytokines expression and activate inflammatory cells. To investigate whether this protein may play a role in the inflammatory events in ALS, we examined both expression and localization of HMGB1 in the lumbar spinal cord of SOD1G93A transgenic mice, a well established mouse model of familial ALS, at different stages of the disease. Intense HMGB1 reactivity was detected in ventral horn motor neurons of both non-transgenic and SOD1G93A mice and there was no difference in its expression between presymptomatic SOD1G93A mice and controls. With the progression of the disease, degenerating neurons showed a reduction of HMGB1 immunoreactivity which could reflect an extracellular release of this protein. By contrast, in the reactive glial cells HMGB1 was remarkably expressed in the nucleus, but not in the cytosol, likely contributing to the proliferation and/or hypertrophy of these cells. These results suggest that HMGB1 may have a different involvement in the motor neurons and glial cells in response to the neurotoxic environment in the spinal cord of SOD1G93A mice, and it may contribute to the progression of inflammatory and neurodegenerative processes.

Section snippets

Acknowledgments

The financial supports of MIUR (project FIRB Negoziali, Protocol RBNEO1B5WW_008) and of the Italian Ministry for Health (RF Malattie Neurodegenerative) are gratefully acknowledged.

References (23)

  • D.W. Cleveland et al.

    From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS

    Nat. Rev. Neurosci.

    (2001)
  • Cited by (49)

    • Implication of HMGB1 signaling pathways in Amyotrophic lateral sclerosis (ALS): From molecular mechanisms to pre-clinical results

      2020, Pharmacological Research
      Citation Excerpt :

      These findings support the pathogenic role of HMGB1 in ALS, suggesting that HMGB1 may be a key player in the pro-inflammatory processes that exacerbate disease progression in ALS. The observed nuclear to cytoplasmic translocation of HMGB1 in the reactive astrocytes and microglia in ALS patients as well as animal models indicates the plausible pathogenic role for HMGB1 in ALS [19,48,49]. It is of no surprise that astrocytes are highly implicated in neurodegeneration and disease progression in ALS [50].

    • The role of HMGB-1 and its inhibitors in brain disorders

      2022, HMGB1: Functions, Inhibitors and Clinical Significance
    View all citing articles on Scopus
    View full text