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DOSE-DEPENDENT REDUCTIONS IN SPATIAL LEARING AND SYNAPTIC FUNCTION IN THE DENTATE GYRUS OF ADULT RATS FOLLOWING DEVELOPMENTAL THYROID HORMONE INSUFFICIENCY.
Citation:
GILBERT, M. E. AND L. SUI. DOSE-DEPENDENT REDUCTIONS IN SPATIAL LEARING AND SYNAPTIC FUNCTION IN THE DENTATE GYRUS OF ADULT RATS FOLLOWING DEVELOPMENTAL THYROID HORMONE INSUFFICIENCY. DEVELOPMENTAL BRAIN RESEARCH. Elsevier Science Ltd, New York, NY, 1069:10-22, (2006).
Impact/Purpose:
To describe the consequences of perinatal hypothyroidism on synaptic function in the hippocampus
Description:
The EPA must evaluate the risk of exposure of the developing brain to chemicals with the potential to disrupt thyroid hormone homeostasis. The existing literature identifies morphological and neurochemical indices of severe neonatal hypothyroidism in the early postnatal period in classic animal models of hypothyroidism. Few data are available on the functional impact of such treatments nor on the long-term effects of early thyroid insufficiency. The following manuscript is the first to describe the consequences of perinatal hypothyroidism on synaptic function in the hippocampus using a standard model thyrotoxicant. This is one of a series of papers that establishes that perturbations in synaptic function exist in a brain region which is critically involved in learning and memory. Here we describe deficits in learning and memory in a standard test of spatial learning in adult offspring of hypothyroid dams. The hormone status has fully recovered at the time of testing. In addition, physiological endpoints of hippocampal synaptic transmission inthe the intact animal are also perturbed in a dose-dependent manner. These data are important for three main reasons: 1) They represent the first dose-response characterization of functional deficits in hippocampal transmission and plasticity in an intact preparation following developmental hormone insufficiency. 2) They show correlative dose-dependent impairments in spatial learning, a hippocampal-dependent task 3) Impairments were observed following moderate degrees of thyroid hormone reductions characteristic of hypothyroxinemia, not frank hypothyroidism in exposed dams. These in vivo observations in synaptic function provide a critical foundation for biologically-based dose response modelling, offer the opportunity to correlate functional deficits in synaptic plasticity to behavioral impairments associated with hypothyroidism, and serve to better refine cellular substrates for further exploration.