title: Neuroprotection of microglial conditioned medium on 6-hydroxydopamine-induced neuronal death: role of transforming growth factor beta-2.
abstract: Microglia, the immune cells of the CNS, play essential roles in both physiological and pathological brain states. Here we have used an in vitro model to demonstrate neuroprotection of a 48 h-microglial conditioned medium (MCM) towards cerebellar granule neurons (CGNs) challenged with the neurotoxin 6-hydroxydopamine, which induces a Parkinson-like neurodegeneration, and to identify the protective factor(s). MCM nearly completely protects CGNs from 6-hydroxydopamine neurotoxicity and at least some of the protective factor(s) are peptidic in nature. While the fraction of the medium containing molecules < 30 kDa completely protects CGNs, fractions containing molecules < 10 kDa or > 10 kDa are not neuroprotective. We further demonstrate that microglia release high amounts of transforming growth factor-beta2 (TGF-beta2) and that its exogenous addition to the fraction of the medium not containing it (< 10 kDa) fully restores the neuroprotective action. Moreover, MCM neuroprotection is significantly counteracted by an inhibitor of TGF-beta2 transduction pathway. Our results identify TGF-beta2 as an essential neuroprotective factor released by microglia in its culture medium that requires to be fully effective the concomitant presence of other factor(s) of low molecular weight.
authors.affiliation: Department of Biology, University of Bologna, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Polazzi
authors.forename: Luis Emiliano Peña
authors.initials: LE
authors.lastname: Altamira
authors.forename: Simona
authors.initials: S
authors.lastname: Eleuteri
authors.forename: Raffaella
authors.initials: R
authors.lastname: Barbaro
authors.forename: Chiara
authors.initials: C
authors.lastname: Casadio
authors.forename: Antonio
authors.initials: A
authors.lastname: Contestabile
authors.forename: Barbara
authors.initials: B
authors.lastname: Monti
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017628:Microglia / Q000502:physiology*; D008970:Molecular Weight; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D053781:Transforming Growth Factor beta2 / Q000502:physiology*
chemical_list: D017077:Culture Media, Conditioned; D018696:Neuroprotective Agents; D053781:Transforming Growth Factor beta2; D016627:Oxidopamine