Original Article

Journal of Neuroimmune Pharmacology

, Volume 5, Issue 2, pp 252-259

Increasing CNS Noradrenaline Reduces EAE Severity

  • Maria Vittoria SimoniniAffiliated withDepartment of Anesthesiology, University of Illinois at ChicagoDepartment of Veterans Affairs, Jesse Brown VA Hospital
  • , Paul E. PolakAffiliated withDepartment of Anesthesiology, University of Illinois at ChicagoDepartment of Veterans Affairs, Jesse Brown VA Hospital
  • , Anthony SharpAffiliated withDepartment of Anesthesiology, University of Illinois at ChicagoDepartment of Veterans Affairs, Jesse Brown VA Hospital
  • , Susan McGuireAffiliated withDepartment of Anesthesiology, University of Illinois at ChicagoDepartment of Veterans Affairs, Jesse Brown VA Hospital
  • , Elena GaleaAffiliated withDepartment of Anesthesiology, University of Illinois at ChicagoDepartment of Veterans Affairs, Jesse Brown VA Hospital
  • , Douglas L. FeinsteinAffiliated withDepartment of Anesthesiology, University of Illinois at ChicagoDepartment of Veterans Affairs, Jesse Brown VA Hospital Email author 

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Abstract

The endogenous neurotransmitter noradrenaline (NA) is known to exert potent anti-inflammatory effects in glial cells, as well as provide neuroprotection against excitatory and inflammatory stimuli. These properties raise the possibility that increasing levels of NA in the central nervous system (CNS) could provide benefit in neurological diseases and conditions containing an inflammatory component. In the current study, we tested this possibility by examining the consequences of selectively modulating CNS NA levels on the development of clinical signs in experimental autoimmune encephalomyelitis (EAE). In mice immunized with myelin oligodendrocyte glycoprotein peptide to develop a chronic disease, pretreatment to selectively deplete CNS NA levels exacerbated clinical scores. Elevation of NA levels using the selective NA reuptake inhibitor atomoxetine did not affect clinical scores, while treatment of immunized mice with the synthetic NA precursor l-threo-3,4-dihydroxyphenylserine (l-DOPS) prevented further worsening. In contrast, treatment of mice with a combination of atomoxetine and l-DOPS led to significant improvement in clinical scores as compared to the control group. The combined treatment reduced astrocyte activation in the molecular layer of the cerebellum as assessed by staining for glial fibrillary protein but did not affect Th1 or Th17 type cytokine production from splenic T cells. These data suggest that selective elevation of CNS NA levels could provide benefit in EAE and multiple sclerosis without influencing peripheral immune responses.

Keywords

multiple sclerosis locus coeruleus catecholamines astrocyte demyelination antidepressant