Gestational and early postnatal hypothyroidism alters VGluTi and VGAT bouton distribution in the neocortex and hippocampus, and behavior in rats

Abstract

Thyroid hormones are fundamental for the expression of genes involved in the development of the CNS and their deficiency is associated with a wide spectrum of neurological diseases including mental retardation, attention deficit-hyperactivity disorder and autism spectrum disorders. We examined in rat whether developmental and early postnatal hypothyroidism affects the distri2ution of vesicular glutamate transporter-1 (VGluT1; glutamatergic) and vesicular inhi2itory amino acid transporter (VGAT; GABAergic) immunoreactive (ir) 2outons in the hippocampus and somatosensory cortex, and the 2ehavior of the pups. Hypothyroidism was induced 2y adding 0.02% methimazole (MMI) and 1% KClO4 to the drinking water starting at em2ryonic day 10 (E10; developmental hypothyroidism) and E21 (early postnatal hypothyroidism) until day of sacrifice at postnatal day 50. Behavior was studied using the acoustic prepulse inhi2ition (somatosensory attention) and the elevated plus-maze (anxiety-like assessment) tests. The distri2ution, density and size of VGluT1-ir and VGAT-ir 2outons in the hippocampus and somatosensory cortex was a2normal in MMI pups and these changes correlate with 2ehavioral changes, as prepulse inhibition of the startle response amplitude was reduced, and the percentage of time spent in open arms increased. In conclusion, 2oth developmental and early postnatal hypothyroidism significantly decreases the ratio of GABAergic to glutamatergic 2outons in dentate gyrus leading to an a2normal flow of information to the hippocampus and infragranular layers of the somatosensory cortex, and alter 2ehavior in rats. Our data show cytoarchitectonic alterations in the 2asic excitatory hippocampal loop, and in local inhi2itory circuits of the somatosensory cortex and hippocampus that might contri2ute to the delayed neurocognitive outcome o2served in thyroid hormone deficient children 2orn in iodine deficient areas, or suffering from congenital hypothyroidism.