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DEVELOPMENTAL HYPOTHYROIDISM REDUCES PARVALBUMIN EXPRESSION IN GABAERGIC NEURONS OF CORTEX AND HIPPOCAMPUS: IMMUNOHISTOCHEMICAL FINDINGS AND FUNCTIONAL CORRELATES.
GILBERT, M. E. AND J. GOODMAN. DEVELOPMENTAL HYPOTHYROIDISM REDUCES PARVALBUMIN EXPRESSION IN GABAERGIC NEURONS OF CORTEX AND HIPPOCAMPUS: IMMUNOHISTOCHEMICAL FINDINGS AND FUNCTIONAL CORRELATES. Presented at 13th International Thyroid Congress, Buenos Aires, ARGENTINA, October 30 - November 04, 2005.
GABAergic interneurons comprise the bulk of local inhibitory neuronal circuitry in cortex and hippocampus and a subpopulation of these interneurons contain the calcium binding protein, parvalbumin (PV). A previous report indicated that severe hypothyroidism reduced PV immunoreactivity (IR) in the neocortex (Berbel et al., 1996). The present study examined GABA-mediated inhibition in the hippocampus, seizure susceptibility, and immunohistochemistry of PV containing interneurons in a rodent model of developmental hypothyroidism. Animals were deprived of thyroid hormone in utero and throughout lactation by exposing pregnant dams to propylthiouracil (PTU) via the drinking water (0, 3, 10 ppm) from GD6 to weaning of the offspring. 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 a dose-dependent reduction in paired pulse depression indicating a suppression of GABA-mediated inhibition. Seizure sensitivity was evaluated by administration of the convulsant, pentylenetetrazol (PTZ, 40mg/kg, ip), to adult offspring. PTU-exposed animals experienced a higher incidence of generalized seizures and seizures were more severe relative to controls. Immunocytochemical staining indicated a reduction in PV-IR in area CA1, dentate gyrus, and neocortex that persisted to adulthood upon return of hormone levels to the control range. A cross-fostering study revealed that only postnatal hormone insufficiency was necessary for reduction in PV staining. These data indicate that developmental thyroid hormone insufficiency alters interneuron expression of PV, compromises GABA-mediated synaptic transmission, and increases seizure sensitivity. (Does not reflect US EPA policy).