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RANTES correlates with inflammatory activity and synaptic excitability in multiple sclerosis.

Francesco Mori1, Robert Nisticò2, Carolina G Nicoletti3

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Regulated upon activation, normal T-cell expressed, and secreted (RANTES) is a pro-inflammatory chemokine that correlates with inflammation and synaptic excitability in multiple sclerosis (MS) brains, impacting disease activity.

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Area of Science:

  • Neuroimmunology
  • Neurophysiology

Background:

  • Inflammatory activity and synaptic transmission alterations are implicated in multiple sclerosis (MS) pathogenesis.
  • Regulated upon activation, normal T-cell expressed, and secreted (RANTES) is a pro-inflammatory chemokine involved in MS.
  • RANTES may influence glutamate release and plasticity in MS, affecting clinical symptoms.

Purpose of the Study:

  • To investigate the role of RANTES in regulating cortical excitability.
  • To correlate RANTES levels with inflammatory markers and disease activity in MS.
  • To examine RANTES's effect on synaptic plasticity in vitro.

Main Methods:

  • Explored RANTES levels in cerebrospinal fluid (CSF) of newly diagnosed MS patients.
  • Assessed associations with MRI and laboratory inflammatory markers.
  • Utilized transcranial magnetic stimulation (TMS) to evaluate cortical excitability and plasticity.
  • Investigated RANTES in mouse hippocampal slices in vitro.

Main Results:

  • CSF RANTES levels were elevated in active MS patients and correlated with interleukin-1β.
  • RANTES levels were associated with TMS-measured cortical synaptic excitability.
  • RANTES did not affect long-term potentiation (LTP)-like plasticity in humans or mice.
  • In vitro, RANTES enhanced basal excitatory synaptic transmission.

Conclusions:

  • RANTES is a biomarker correlating with inflammation and synaptic excitability in MS.
  • RANTES enhances basal excitatory synaptic transmission but does not affect LTP in the hippocampus.
  • Findings suggest RANTES's role in MS-related cortical hyperexcitability.