Thyroid hormones are involved in the structural as well as functional development of the newborn brain. A deficiency of these hormones during the neonatal phase leads to a decreased neuronal excitability and a slowing of mental functions.

We have previously shown that the thyroid hormone T3 (triiodo-L-thyronne) regulates voltage-activated sodium-currents (I_nav) in hippocampal neurons from neonatal rat brains. The regulation was shown to depend on the release of soluble factors by glia cells and we identified basic fibroblast growth factor (FGF-2) as the potential main factor involved in the regulation of I_nav (Niederkinkhaus et al., 2009).

Since Trentin et al. (2001) presented evidence for the release of additional factors from glial cells we now investigated the potential contribution of Neurotrophin-3 (NT-3) to the regulation of sodium currents.

Using the whole cells patch clamp technique we found that a preincubation of neuron-enriched hippocampal cultures with (7 nM) NT-3 for 4 days increased the I_nav by 40 %. This upregulation was blocked by coincubation with 10 nM of the trk-receptor blocker K252a or by addition of 3 µg of anti-NT-3 antibodies to the culture dishes.

Surprisingly, a coincubation with K252a, as well as anti NT-3 antibodies potentiated the upregulation of I_nav by T3 as well as by FGF-2.

These results support the hypothesis that FGF-2 is the mayor factor in the T3- induced upregulation of sodium currents. A co-secretion of NT-3 could in turn limit the up- regulation of I_nav by T3 secreted FGF-2. These results, showing the interaction of several factors on I_nav regulation could also be a first explanation for the observed variability of T3 effects on brain function.