Effects of 3-iodothyronamine (T1AM) on signaling pathways involved in synaptic plasticity and neuroprotection.

In mouse, the administration of 3-iodothyronamine (T1AM) had an antiamnestic and prolearning effect. In addition, T1AM rescued long term potentiation (LTP) in enthorinal cortex exposed to the toxic effect of β-amyloid. In the present paper we used a neuronal cell line to evaluate the effect of T1AM on the expression calcium calmodulin dependent kinase II (CamKII) and protein kinase C (PKC), two key players involved in LTP. The effects on sirtuin 1 (SIRT1), allegedly responsible for the neuroprotective effect of resveratrol, were also investigated. Methods: A hybrid line of cancer cells of mouse neuroblastoma and rat glioma (NG108-15) was used and treated with 100 nM to 10 M T1AM for 24 h, alone or in combination with 10 µM resveratrol and/or 10 µM amyloid β peptide (25-35). Protein expression and post-translational modifications were investigated by Western blot technique. Glucose consumption was also measured upon 4 h treatment. Results: NG108-15 expressed TAAR1, the putative T1AM receptor, as well as AMPA and NMDA receptors, that are involved in the signaling cascade responsible of LTP. T1AM (10 M) induced CaMKII phosphorylation (p<0.001), but had no direct effect on PKC and SIRT1 expression. However, in the presence of β-amyloid, T1AM increased PKC and SIRT 1 expression at 1M and 10 M concentration, respectively, although β-amyloid alone had no significant effect. The response to resveratrol was also modified by T1AM, since resveratrol inhibited PKC expression while the association of resveratrol and T1AM (100 nM) produced a remarkable increase vs the baseline (P<0.05). Furthermore an increase in glucose consumption was observed at the highest T1AM concentration (p<0.01). Conclusions: In NG108-15 cells T1AM activated CaMKII and had complex effects on the response to β-amyloid and resveratrol.