Subventricular zone neural progenitors reverse TNF-alpha effects in cortical neurons.
BACKGROUND
Tumor necrosis factor alpha (TNFα) plays a physiological role in controlling synaptic transmission and plasticity in the healthy central nervous system by modulating glutamate receptor trafficking to the plasma membrane. TNFα expression is also rapidly induced in response to tissue injury and infection. By promoting the insertion of Ca(2+) permeable-AMPA receptors into the neuronal plasma membrane, this cytokine may cause excessive Ca(2+) influx into neurons, thus enhancing neuronal death.


METHODS
Primary cultures of cortical neurons were obtained from E18 foetal mice and incubated for 24 h with adult neural stem cells (aNPCs) either stimulated with lipopolysaccharide (LPS(+)aNPCs) or not (aNPCs). Cultures were treated with TNFα (100 ng/ml), and electrophysiological recordings were performed in different conditions to evaluate the effect of the cytokine on neuronal transmission.


RESULTS
In this study, we demonstrate that aNPCs from the subventricular zone reverse the effects induced by the cytokine. Moreover, we show that the effect of aNPCs on cortical neurons is mediated by cannabinoid CB1 receptor activation.


CONCLUSIONS
These data suggest that the role of aNPCs in preventing excitatory neurotransmission potentiation induced by TNFα on cortical neurons may have important implications for pathologies characterized by an inflammatory component affecting cortical neurons such as Alzheimer's disease.
Department of Medical Biotechnology and Traslational Medicine, University of Milano, via Vanvitelli 32, 20129, Milan, Italy. raffaella.morini@humanitasresearch.it.|Humanitas Clinical and Research Center, via Manzoni 56, 20089, Rozzano, Italy. raffaella.morini@humanitasresearch.it.
Raffaella
R
Morini
Department of Medical Biotechnology and Traslational Medicine, University of Milano, via Vanvitelli 32, 20129, Milan, Italy. elsa.ghirardini@humanitasresearch.it.|Humanitas Clinical and Research Center, via Manzoni 56, 20089, Rozzano, Italy. elsa.ghirardini@humanitasresearch.it.
Elsa
E
Ghirardini
Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute and University, Via Olgettina 58, 20132, Milan, Italy. butti.erica@hsr.it.
Erica
E
Butti
Humanitas Clinical and Research Center, via Manzoni 56, 20089, Rozzano, Italy. c.verderio@in.cnr.it.|National Research Council, Institute of Neuroscience, via Vanvitelli 32, 20129, Milan, Italy. c.verderio@in.cnr.it.
Claudia
C
Verderio
Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute and University, Via Olgettina 58, 20132, Milan, Italy. martino.gianvito@hsr.it.
Gianvito
G
Martino
Humanitas Clinical and Research Center, via Manzoni 56, 20089, Rozzano, Italy. michela.matteoli@humanitasresearch.it.|National Research Council, Institute of Neuroscience, via Vanvitelli 32, 20129, Milan, Italy. michela.matteoli@humanitasresearch.it.
Michela
M
Matteoli
D000818:Animals; D002478:Cells, Cultured; D020547:Lateral Ventricles / Q000166:cytology; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha