A synthetic cannabinoid agonist promotes oligodendrogliogenesis during viral encephalitis in rats

Marylou V. Solbrig, Yijun Fan, Neal Hermanowicz, Maria Grazia Morgese, Andrea Giuffrida

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Chronic CNS infection by several families of viruses can produce deficits in prefrontal cortex (PFC) and striatal function. Cannabinoid drugs have been long known for their anti-inflammatory properties and their ability to modulate adult neuro and gliogenesis. Therefore, we explored the effects of systemic administration of the cannabinoid agonist WIN55,212-2(WIN) on prefrontal cortex (PFC) and striatal cytogenesis in a viral model of CNS injury and inflammation based on Borna Disease (BD) virus encephalitis. Active BrdU+ progenitor populations were significantly decreased 1week after BrdU labeling in BD rats [p<0.001 compared to uninfected (NL) controls] while less than 5% of BrdU+ cells colabeled for BDV protein. Systemic WIN (1mg/kg i.p. twice daily×7days) increased the survival of BrdU+ cells in striatum (p<0.001) and PFC of BD rats, with differential regulation of labeled oligodendroglia precursors vs microglia/macrophages. WIN increased the percentage of BrdU+ oligodendrocyte precursor cells and decreased BrdU+ ED-1-labeled phagocytic cells, without producing pro- or antiviral effects. BDV infection decreased the levels of the endocannabinoid anandamide (AEA) in striatum (p<0.05 compared to NL rats), whereas 2-AG levels were unchanged. Our findings indicate that: 1) viral infection is accompanied by alterations of AEA transmission in the striatum, but new cell protection by WIN appears independent of its effect on endocannabinoid levels; and 2) chronic WIN treatment alters the gliogenic cascades associated with CNS injury, promoting oligodendrocyte survival. Limiting reactive gliogenesis and macrophage activity in favor of oliogodendroglia development has significance for demyelinating diseases. Moreover, the ability of cannabinoids to promote the development of biologically supportive or symbiotic oligodendroglia may generalize to other microglia-driven neurodegenerative syndromes including NeuroAIDS and diseases of aging.

Original languageEnglish (US)
Pages (from-to)231-241
Number of pages11
JournalExperimental Neurology
Volume226
Issue number1
DOIs
StatePublished - Nov 1 2010

Keywords

  • Anandamide
  • Borna disease virus
  • BrdU
  • Endocannabinoid
  • Neurogenesis
  • WIN55,212-2

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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