Non genomic modulation of ligand gated ionotropic receptors by thyroid hormones

Ligand gated ionotropic receptors are responsible for the fast neurotransmission in the brain and are the target of widely used drugs, such as anxiolytics, anticonvulsant and antidepressant, and of endogenously produced substances, e.g. hormones. In this review, the fast regulatory effects of thyroid hormones (THs, T3 and T4) on ligand gated ion channels will be analyzed and discussed. More precisely, the focus will be on receptors that mediate the majority of inhibitory and excitatory neurotransmission in the brain, respectively γ-aminobutyric acid (GABA) and glutamate ionotropic receptors.Brain is an important target of THs, as proved by profound alterations in its functionality related to hormonal imbalance. Indeed, dysthyroidism is often associated with several neuropsychiatric disorders that derive also from a dysfunction of GABAergic and glutamatergic neurotransmission. The molecular mechanisms responsible for these changes are not completely clarified yet. THs, through the binding of nuclear receptors, can modulate the expression of proteins directly or indirectly involved in neurotransmission; in addition, their non genomic fast modulation of ionotropic receptors mediating excitatory and inhibitory neurotransmission could also play an important role.THs modulate recombinant and native receptors activated by exogenous GABA or glutamate as well synaptic and extrasynaptic excitatory and inhibitory neurotransmission. These non genomic effects do not depend on protein phosphorylation or on the membrane integrin receptor αvβ3 activation.Keeping in mind that a local regulation of THs levels can occur in different brain regions the fast modulation of THs of synaptic activity could provide a rapid and efficacious control of the function of several brain circuitries.