Serotonin-insulin signaling cross-talk in a human neuronal cell line and hippocampal slices

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 842-862-Insulin Signaling & Action
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-861
Mohammed Taouis*1, Ioannis Papazoglou2, Nicolas Vicaire2, Alain Aubourg2, Kyriaki Gerozissis2 and claire-Marie Vacher2
1University of Paris XI, Chilly Mazarin, France, 2University of Paris-Sud
Serotonin-insulin signaling cross-talk in a human neuronal cell line and hippocampal slices

Ioannis Papazoglou1,2, Nicolas Vicaire1,2, Alain Aubourg1,2,  Kyriaki Gerozissis1,2, Mohammed Taouis1,2, Claire-Marie Vacher1,2

1 Neuroendocrinologie Moléculaire de la Prise Alimentaire, University of Paris-Sud, UMR 8195, Orsay, F-91405, France

2 Neuroendocrinologie Moléculaire de la Prise Alimentaire, CNRS, Centre de Neurosciences Paris-Sud UMR8195, Orsay, F-91405, France

Accumulated evidence supports that depression can result from a decrease in available serotonin or inefficient serotonin signaling in the brain, and that its prevalence is 1,5 to 3 times higher in patients suffering from type 2 diabetes, which is associated with central insulin resistance, than in the general population. Both serotonin and insulin can act in the brain via the activation of phosphoinositide-3-kinase (PI3K)/Akt signaling pathway. In order to evaluate whether insulin resistance state can affect serotonin sensitivity in neurons, we studied the possible cross-talk between serotonin and insulin signaling pathways in a human neuronal cell line and hippocampal slices.

In differentiated human neuroblastoma cells (SH-SY5Y), we showed that serotonin and insulin both induced Akt phosphorylation, and had an additive effect when administered together. Interestingly, cells pretreatment with insulin (16h, prior acute treatment) completely abolished Akt phosphorylation in response to insulin and serotonin. In addition, we showed that serotonin-dependent Akt phosphorylation was completely inhibited in the presence of a PI3K inhibitor. This suggests, as for insulin, that serotonin activates Akt through a PI3K-dependent mechanism.

Further, we investigated the activation of Akt and its substrate, GSK3β, in hippocampal slices. Insulin and serotonin treatment increased the levels of phosphorylated Akt and GSK3β in hippocampal neurons of control animals and this effect was impaired in the presence of a PI3K inhibitor. In addition, hippocampal slices from rats fed high fat diet (HFD), known to be insulin-resistant, were treated with insulin or serotonin. Akt and GSK3β phosphorylation was deeply impaired in slices from HFD rats when insulin or serotonin was applied. This indicates that the insulin-resistance state established in these hippocampal slices decreased also their sensitivity to serotonin.

In conclusion, our study shows that serotonin can directly induce a PI3K-dependent Akt phosphorylation in neurons, which is abolished when insulin resistance state occurs. This suggests a possible cross-talk between insulin- and serotonin-activated signaling pathways that may account, at least in part, for the association between type 2 diabetes and depression.

Nothing to Disclose: MT, IP, NV, AA, KG, CMV

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