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Subventricular zone neural progenitors reverse TNF-alpha effects in cortical neurons.

Morini R, Ghirardini E, Butti E, Verderio C, Martino G, Matteoli M - Stem Cell Res Ther (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biotechnology and Traslational Medicine, University of Milano, via Vanvitelli 32, 20129, Milan, Italy. raffaella.morini@humanitasresearch.it.

ABSTRACT

Introduction: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

TNFα increases mEPSC frequency and amplitude in cortical neurons. a Examples of voltage-clamp recordings of mEPSCs from cultured cortical neurons in control conditions, upon treatment with TNFα (100 ng/ml 30 min) or in the presence of TNFα and neutralizing Abs (0.5 μg/ml; R&D Systems) (calibration bars: 20 pA, 200 ms). b, c Group data of average mEPSC amplitude and frequency in untreated (n = 15), TNFα-treated (n = 13), and TNFα plus neutralizing Ab-treated (n = 10) cells. A significant increase in average mEPSC amplitude and frequency is produced by TNFα, completely blocked by neutralizing anti -TNFα Abs (P < 0.05). All data are expressed as mean ± standard error of the mean. Statistical test: one-way analysis of variance, Dunn’s multiple comparisons test. Ab antibody, mEPSC miniature excitatory post-synaptic current, TNFα tumor necrosis factor alpha
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Fig1: TNFα increases mEPSC frequency and amplitude in cortical neurons. a Examples of voltage-clamp recordings of mEPSCs from cultured cortical neurons in control conditions, upon treatment with TNFα (100 ng/ml 30 min) or in the presence of TNFα and neutralizing Abs (0.5 μg/ml; R&D Systems) (calibration bars: 20 pA, 200 ms). b, c Group data of average mEPSC amplitude and frequency in untreated (n = 15), TNFα-treated (n = 13), and TNFα plus neutralizing Ab-treated (n = 10) cells. A significant increase in average mEPSC amplitude and frequency is produced by TNFα, completely blocked by neutralizing anti -TNFα Abs (P < 0.05). All data are expressed as mean ± standard error of the mean. Statistical test: one-way analysis of variance, Dunn’s multiple comparisons test. Ab antibody, mEPSC miniature excitatory post-synaptic current, TNFα tumor necrosis factor alpha

Mentions: Although several studies have shown that TNFα increases synaptic strength at hippocampal excitatory synapses by rapidly inserting AMPA receptors via TNFR1 receptor activation [30], little has been reported in different neuronal cell types [31, 32]. To address whether this effect is restricted to hippocampal neurons or also occurs at cortical synapses, we grew cultures of primary neurons derived from the cerebral cortex and exposed them to TNFα (100 ng/ml) for 30 min before recording mEPSCs. Our data showed a significant increase in both frequency and amplitude of mEPSCs in TNFα-treated neurons with respect to untreated control neurons (Fig. 1). This effect was completely blocked in the presence of neutralizing TNFα antibodies. These data indicate that cortical neurons respond to TNFα in a manner that is similar to hippocampal neurons and indicate that this cytokine may predispose cortical neurons to excitotoxic phenomena.Fig. 1


Subventricular zone neural progenitors reverse TNF-alpha effects in cortical neurons.

Morini R, Ghirardini E, Butti E, Verderio C, Martino G, Matteoli M - Stem Cell Res Ther (2015)

TNFα increases mEPSC frequency and amplitude in cortical neurons. a Examples of voltage-clamp recordings of mEPSCs from cultured cortical neurons in control conditions, upon treatment with TNFα (100 ng/ml 30 min) or in the presence of TNFα and neutralizing Abs (0.5 μg/ml; R&D Systems) (calibration bars: 20 pA, 200 ms). b, c Group data of average mEPSC amplitude and frequency in untreated (n = 15), TNFα-treated (n = 13), and TNFα plus neutralizing Ab-treated (n = 10) cells. A significant increase in average mEPSC amplitude and frequency is produced by TNFα, completely blocked by neutralizing anti -TNFα Abs (P < 0.05). All data are expressed as mean ± standard error of the mean. Statistical test: one-way analysis of variance, Dunn’s multiple comparisons test. Ab antibody, mEPSC miniature excitatory post-synaptic current, TNFα tumor necrosis factor alpha
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4562198&req=5

Fig1: TNFα increases mEPSC frequency and amplitude in cortical neurons. a Examples of voltage-clamp recordings of mEPSCs from cultured cortical neurons in control conditions, upon treatment with TNFα (100 ng/ml 30 min) or in the presence of TNFα and neutralizing Abs (0.5 μg/ml; R&D Systems) (calibration bars: 20 pA, 200 ms). b, c Group data of average mEPSC amplitude and frequency in untreated (n = 15), TNFα-treated (n = 13), and TNFα plus neutralizing Ab-treated (n = 10) cells. A significant increase in average mEPSC amplitude and frequency is produced by TNFα, completely blocked by neutralizing anti -TNFα Abs (P < 0.05). All data are expressed as mean ± standard error of the mean. Statistical test: one-way analysis of variance, Dunn’s multiple comparisons test. Ab antibody, mEPSC miniature excitatory post-synaptic current, TNFα tumor necrosis factor alpha
Mentions: Although several studies have shown that TNFα increases synaptic strength at hippocampal excitatory synapses by rapidly inserting AMPA receptors via TNFR1 receptor activation [30], little has been reported in different neuronal cell types [31, 32]. To address whether this effect is restricted to hippocampal neurons or also occurs at cortical synapses, we grew cultures of primary neurons derived from the cerebral cortex and exposed them to TNFα (100 ng/ml) for 30 min before recording mEPSCs. Our data showed a significant increase in both frequency and amplitude of mEPSCs in TNFα-treated neurons with respect to untreated control neurons (Fig. 1). This effect was completely blocked in the presence of neutralizing TNFα antibodies. These data indicate that cortical neurons respond to TNFα in a manner that is similar to hippocampal neurons and indicate that this cytokine may predispose cortical neurons to excitotoxic phenomena.Fig. 1

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biotechnology and Traslational Medicine, University of Milano, via Vanvitelli 32, 20129, Milan, Italy. raffaella.morini@humanitasresearch.it.

ABSTRACT

Introduction: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus