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GABA FUNCTION IS ALTERED FOLLOWING DEVELOPMENTAL HYPOTHYROIDISM: NEUROANATOMICAL AND NEUROPHYSIOLOGICAL EVIDENCE.
Citation:
Gilbert, M. E., L. Sui, S. Thomas, S. N. Smoller, J. Schon, AND J. Goodman. GABA FUNCTION IS ALTERED FOLLOWING DEVELOPMENTAL HYPOTHYROIDISM: NEUROANATOMICAL AND NEUROPHYSIOLOGICAL EVIDENCE. Presented at Society of Toxicology, New Orleans, LA, March 06 - 10, 2005.
Description:
Thyroid hormone deficiency during development produces changes in the structure of neurons and glial cells and alters synaptic function in the hippocampus. GABAergic interneurons comprise the bulk of local inhibitory neuronal circuitry and a subpopulation of these interneurons contain the calcium binding protein, parvalbumin (PV). A previous report indicated that severe hypothyroidism reduced PV staining in the neocortex (Berbel et al., 1996). The present study examined GABA-mediated inhibition and immunocytochemistry of PV-containing interneurons in the dentate gyrus of the hippocampal formation. Animals were deprived of thyroid hormone in utero and throughout lactation by exposing pregnant dams to propylthiouricil (PTU) via the drinking water (0, 3, 10 ppm) from GD 6 to weaning of the offspring. This regimen reduced maternal serum T4, increased TSH and had no effect on T3 at the low dose. Both T3 and T4 were reduced in the offspring at weaning but returned to control levels in adulthood. Synaptic inhibition of the perforant path-dentate gyrus synapse was evaluated using in vivo field potentials and paired pulse techniques in adult offspring. PTU-induced reduction in paired pulse depression and augmentation in facilitation were observed, indicating a suppression of GABA-mediated inhibition. Immunocytochemical staining for PV was reduced in the dentate gyrus and the neocortex. A cross-fostering study revealed that postnatal hormone deficiency was required for an alteration in PV staining. Altered staining persisted to adulthood despite return of thyroid hormones to control levels. These data indicate that thyroid hormone insufficiency during the early postnatal period alters interneuron expression of PV and compromises GABA-mediated synaptic transmission. (Funded by USEPA, does not reflect US EPA policy).