Propylthiouracil (PTU)-induced hypothyroidism in the developing rat impairs synaptic transmission and plasticity in the dentate gyrus of the adult hippocampus.
Reductions in thyroid hormone during critical periods of brain development can have devastating effects on neurological function that are permanent. Neurochemical, molecular and structural alterations in a variety of brain regions have been well documented, but little information is available on the consequences of developmental hypothyroidism on synaptic function. Developing rats were exposed to the thyrotoxicant, propylthiouracil (PTU: 0 or 15 ppm), through the drinking water of pregnant dams beginning on GD18 and extending throughout the lactational period. Male offspring were allowed to mature after termination of PTU exposure at weaning on PND21 and electrophyiological assessments of field potentials in the dentate gyrus were conducted under urethane anesthesia between 2 and 5 months of age. PTU dramatically reduced thyroid hormones on PND21 and produced deficits in body weight that persisted to adulthood. Synaptic transmission was impaired as evidenced by reductions in excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitudes at a range of stimulus intensities. Long-term potentiation of the EPSP slope was impaired at both modest and strong intensity trains, whereas a paradoxical increase in PS amplitude was observed in PTU-treated animals in response to high intensity trains. These data are the first to describe functional impairments in synaptic transmission and plasticity in situ as a result of PTU treatment and suggest that perturbations in synaptic function may contribute to learning deficits associated with developmental hypothyroidism.
D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000963:Antimetabolites / Q000633:toxicity; D001835:Body Weight; D018891:Dentate Gyrus / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D006624:Hippocampus / Q000473:pathology; D007037:Hypothyroidism / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011441:Propylthiouracil / Q000633:toxicity*; D011863:Radioimmunoassay; D051381:Rats; D020318:Rats, Long-Evans; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013963:Thyroid Hormones / Q000097:blood
D000963:Antimetabolites; D013963:Thyroid Hormones; D011441:Propylthiouracil