EPA Science Inventory

IMPAIRMENT IN SHORT-TERM BUT ENHANCED LONG-TERM SYNAPTIC POTENTIATION AND ERK ACTIVATION IN ADULT HIPPOCAMPAL AREA CA1 FOLLOWING DEVELOPMENTAL HYPOTHYROIDISM.

Citation:

Sui, L., W L. Anderson, AND M. E. GILBERT. IMPAIRMENT IN SHORT-TERM BUT ENHANCED LONG-TERM SYNAPTIC POTENTIATION AND ERK ACTIVATION IN ADULT HIPPOCAMPAL AREA CA1 FOLLOWING DEVELOPMENTAL HYPOTHYROIDISM. TOXICOLOGICAL SCIENCES. Society of Toxicology, 85:647-656, (2005).

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. Limited information is available on the functional impact of such treatments, the long-term effects of early thyroid insufficiency, and the hazards associated with subtle perturbations of the thyroid system during critical periods of brain development. This manuscript is a followup to a previous publication describing the of developmental hypothyroidism on synaptic transmission and plasticity in the hippocampus, a brain region critical for learning and memory. Previous work evaluated hypothyroid effects in the neonate during a period of active hormone insufficiency (Sui and Gilbert, 2003). The present paper reports on the long-term changes of developmental hormone reductions in the adult animal following return to normal hormone status. Dose-dependent perturbations in synaptic function are described that are persistent and are associated with alterations in signal transduction of a key enzyme in synaptic plasticity. This is the first report of altered mitogen activated protein kinase (MAPK) activation in a developmental hypothyroid model and represents a potential mechanism of the lingering functional impairments associated with early hormone insufficiency. This is one of a series of papers that will initially establish the perturbations in synaptic function in this brain region and eventually link these functional impairments at the synaptic level to behavioral deficits, neurochemical substrates, and morphological abberations in brain structure.

Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Start Date: 02/01/2005
Completion Date: 02/01/2005
Record Last Revised: 12/21/2005
Record Created: 12/08/2004
Record Released: 12/08/2004
Record ID: 104810

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

NEUROTOXICOLOGY DIVISION

NEUROPHYSIOLOGICAL TOXICOLOGY BRANCH