TOPIC: In primary neuron cultures (hippocampus), glutamatergic receptors are affected by thyroid hormones
Title: Non genomic regulation of glutamatergic neurotransmission in hippocampus by thyroid hormones.
Authors: Losi G, Garzon G, & Puia G.
Reference: Neuroscience 151: 155-163, 2008
Thyroid hormones (THs) are well known for their genomic effects but, recently, attention has focused also on their non-genomic actions as rapid modulators of membrane receptors. There is substantial evidence also for a complex interaction between the GABAergic system and THs. The hippocampus is a substrate for some forms of learning and memory and sensitive to THs.
Because of the link between THs and brain excitability, the authors investigated the direct non-genomic effect of these hormones on ionotropic glutamate receptors expressed in hippocampal neurons grown in culture and in acutely dissociated hippocampal slices.
Primary culture of hippocampal neurons were prepared from newborn (postnatal day (PD) 1) Sprague'Dawley rats. Electrophysiological recordings were performed at room temperature, under voltage clamp in the whole-cell configuration of the patch-clamp technique.
The authors show that T4 and T3 rapidly decrease N-methyl-D-aspartate (NMDA)-evoked currents in rat hippocampal cultures with potency in the micromolar range. The effect is not mediated by glutamate or glycine binding sites, as an increase in agonist or glycine concentration does not alter TH potencies. Furthermore, THs' effect on NMDA receptors is independent of voltage and subunit composition. The mechanism of THs' antagonistic effect does not involve PKC phosphorylation of NMDA receptors since neither blocking nor stimulating PKC changed THs' modulation. T3, but not T4, inhibits also kainate-evoked currents in hippocampal neurons in culture. In hippocampal pyramidal neurons in slice, T3, but not T4, significantly reduced the frequency of miniature excitatory postsynaptic currents (mEPSCs) without affecting their amplitude and decay.
Thyroid hormones can rapidly affect ionotropic glutamatergic receptors in hippocampal neurons, an effect that could have an important role in their modulation of brain function in physiological and pathological states.
Thyroid hormone (TH) action in the brain is a complex summation of both genomic and non-genomic effects. Major developmental abnormalities of the nervous system are associated with deprivation or excess of TH in the developing brain. Behavioural and neurological effects are seen with perturbations of TH levels in the adult brain. It has been hypothesized by others that the main effects of TH are on the developing brain and likely mediated through genomic effect. However, the effect of TH on neurotransmission in the adult brain is likely to be non-genomic.
The data presented by Losi et al. suggest that TH may play a direct effect via non-genomic pathways on glutamatergic receptors in the hippocampus. Furthermore, these authors demonstrate that T3 (and not T4) is likely to have these non-genomic effects. This raises the question as to the role of exogenous T3 on behaviour and normal brain physiology.
On a somewhat more anecdotal standpoint, it might fuel the fire ' slightly ' that maybe psychiatrists aren't so crazy when they give T3 to patients for improvement of psychological or behavioural disturbances. Summary and commentary prepared by Roy Weiss (Related to Chapter 3 of TDM)