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Moderate Perinatal Thyroid Hormone Insufficiency Alters Visual System Function in Adult Rats
Citation:
Boyes, W., L. Degn, BJ George, AND M. Gilbert. Moderate Perinatal Thyroid Hormone Insufficiency Alters Visual System Function in Adult Rats. NEUROTOXICOLOGY. Elsevier B.V., Amsterdam, Netherlands, 67:73-83, (2018).
Impact/Purpose:
In conclusion, the results of the present experiments provide the first quantitative information on the decreased function of the adult visual system in a rodent model of moderate developmental thyroid disruption. Impairments of the retina and higher level visual processing centers are implicated. Functional consequences at the retina are consistent with retinal pathology reported with more severe hypothyroid insults. Functional consequences of visual contrast perception are consistent with reports in humans. The results demonstrate the vulnerability of the developing visual system to degrees of TH insufficiency that have previously been reported to impair other sensory systems in rodents, and add experimental support to human reports that perinatal hormone dysfunction impairs visual contrast perception and visuospatial processing in children.
Description:
Thyroid hormone (TH) is critical for many aspects of neurodevelopment, such as the visual system, but may be disrupted by many environmental contaminants. The experimental data demonstrating a role for TH on visual system development generally derives from studies in which developing pups were completely deprived of TH. These data are difficult to interpret for the potential risks of environmental exposures, which might produce dose-related, graded, or moderate TH reductions. The goal of the current experiments is to explore dose-response relations between graded inhibition of TH during development and the visual function of the grown offspring. Pregnant Long Evans rats received 0 or 3 ppm (Experiment 1), or 0, 1, 2, or 3 ppm (Experiment 2) of propylthiouracil (PTU), a known inhibitor of thyroid hormone synthesis, in drinking water from gestation day (GD) 6 to-postnatal day (PN) 21. Treatment with PTU caused dose-related reductions of serum T4 in dams, with rapid recovery on termination of exposure, and euthyroidism by the time of visual function testing. As adults, offspring underwent a series of visual function tests including electroretinograms (ERGs) (Experiment 1) and visual evoked potentials (VEPs) (Experiments 1 and 2). When ERGs were recorded in dark-adapted rats to a series of increasing luminance flashes the ERG a-wave, generated by rod photoreceptors, was increased in amplitude in the PTU-treated group. ERGs recorded to a green stimulus flickering at 21Hz, intended to reflect the function of M-cone photoreceptors, were reduced in amplitude by PTU treatment, but UV-flicker ERGS (S-cones) were not systematically altered. The amplitudes of VEPs elicited by visual pattern alternations across a range of values of visual stimulus contrast were significantly reduced by 2 or 3 ppm PTU. The slope of VEP amplitude-log contrast functions was reduced by PTU in a manner that suggested impairment of visual contrast gain mechanisms. Visual contrast gain primarily reflects visual cortex function, and is responsible for adjusting sensitivity of perceptual mechanisms in response to changing visual scenes. The results indicate that moderate levels of pre-and post-natal TH insufficiency led to alterations in visual function of adult rats, including both retinal and visual cortex sites of dysfunction.
