3-iodothyronamine (T1AM) induces changes on glutamatergic postsynaptic signaling pathway

Objective: Exogenous 3-iodothyronamine (T1AM), a derivative of thyroid hormone, produces antiamnestic and prolearning effects in mice. Glutamatergic neurotransmission, the major excitatory system in brain, plays a key role in regulating neuroplasticity, learning and memory, and it is often compromised in neurological disorders. In the present work, we characterized the gene expression profile of two different neuronal cell lines and we evaluated the effects of T1AM on the expression of proteins involved in glutamatergic signaling pathway. Methods: A hybrid line of cancer cells of mouse neuroblastoma and rat glioma (NG108-15) and a human glioblastoma cell line (U-87 MG) were used. We first characterized the in vitro model by analyzing gene expression of several proteins involved in the glutamatergic postsynaptic cascade by real time PCR. Cell lines were then treated with T1AM for 24h, ranging from 0.1 to 10 μM, alone or in combination with 10 µM resveratrol (RSV) and/or 10 µM amyloid β peptide (25-35). Cell viability, glucose consumption, protein expression, (cell calcium content) and cAMP production were assessed. Results: NG108-15 and U-87 MG cell lines expressed receptors and other proteins belonging to the glutamatergic post synaptic signaling pathway, while only U87 cells expressed TAAR1, one of the putative T1AM receptors. In NG 108-15 cells, T1AM in combination with RSV upregulated PKC protein expression vs the baseline (P<0.05). Furthermore, in the same cell line, T1AM decreased glucose consumption (p<0.01 vs control), without affecting cell viability. In U-87 MG cells, T1AM improved pCREB/CREB ratio (p<0.01) without altering glucose consumption. Cell viability and cAMP concentration were significantly increased at 0.1 M T1AM. Conclusions: Our results show that in in vitro models of neuronal cells T1AM may produce changes in the post synaptic signaling cascade of the glutamatergic system.