title: 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.
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.
authors.affiliation: Department of Veterinary-Physiology and -Biochemistry, Justus-Liebig University Giessen, Frankfurter Strasse 100, D-35392 Giessen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ott
authors.forename: Florian
authors.initials: F
authors.lastname: Wuchert
authors.forename: Jolanta
authors.initials: J
authors.lastname: Murgott
authors.forename: Christoph
authors.initials: C
authors.lastname: Rummel
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Gerstberger
authors.forename: Joachim
authors.initials: J
authors.lastname: Roth
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D031608:Area Postrema / Q000098:blood supply / Q000166:cytology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D005260:Female; D007031:Hypothalamus / Q000098:blood supply / Q000166:cytology*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000166:cytology / Q000187:drug effects; D018716:Molecular Mimicry; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D011070:Poly I-C / Q000494:pharmacology*; D061251:Primary Cell Culture; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D015850:Interleukin-6; D011956:Receptors, Cell Surface; C530472:TLR3 protein, rat; D051196:Toll-Like Receptor 3; D014409:Tumor Necrosis Factor-alpha; C045250:poly I-C receptor; D011070:Poly I-C