The viral mimetic polyinosinic:polycytidylic acid (poly I:C) induces cellular responses in primary cultures from rat brain sites with an incomplete blood-brain barrier

Neurosci Lett. 2012 Nov 14;530(1):64-8. doi: 10.1016/j.neulet.2012.09.038. Epub 2012 Sep 27.

Abstract

Primary microcultures of the organum vasculosum laminae terminalis (OVLT) and the area postrema (AP), brain sites with an incomplete blood-brain barrier, were established from topographically excised rat pup tissue, with cellular identification by marker protein-specific immunocytochemistry. Employing the ratio calcium imaging technique, we showed for the first time that polyinosinic:polycytidylic acid (poly I:C) can induce calcium signalling in single OVLT and AP cells. Poly I:C stimulation caused fast, transient rises in intracellular calcium in about 5% of neurons and astrocytes and some microglial cells. Frequently, the responses of astrocytes and microglial cells showed a shorter onset-latency compared to neurons. In addition, exposure to poly I:C led to a time dependent release of bioactive tumour necrosis factor (TNF) and interleukin-6 (IL-6) into the supernatants of OVLT and AP cultures. The demonstration of direct cellular responses of OVLT- and AP-intrinsic cells to stimulations with poly I:C is in agreement with the discovered existence of Toll-like receptor 3 (TLR3), the cognate receptor for poly I:C, in the brain.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Area Postrema / blood supply
  • Area Postrema / cytology*
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Blood-Brain Barrier / physiology*
  • Calcium Signaling / drug effects*
  • Calcium Signaling / physiology
  • Female
  • Hypothalamus / blood supply
  • Hypothalamus / cytology*
  • Interleukin-6 / metabolism
  • Male
  • Microglia / cytology
  • Microglia / drug effects
  • Molecular Mimicry
  • Neuroimmunomodulation / drug effects
  • Neuroimmunomodulation / physiology
  • Neurons / cytology
  • Neurons / drug effects*
  • Poly I-C / pharmacology*
  • Primary Cell Culture
  • Rats
  • Receptors, Cell Surface / metabolism
  • Toll-Like Receptor 3 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antiviral Agents
  • Interleukin-6
  • Receptors, Cell Surface
  • TLR3 protein, rat
  • Toll-Like Receptor 3
  • Tumor Necrosis Factor-alpha
  • poly I-C receptor
  • Poly I-C