title: Adult onset-hypothyroidism: alterations in hippocampal field potentials in the dentate gyrus are largely associated with anaesthesia-induced hypothermia.
abstract: Thyroid hormone (TH) is essential for a number of physiological processes and is particularly critical during nervous system development. The hippocampus is strongly implicated in cognition and is sensitive to developmental hypothyroidism. The impact of TH insufficiency in the foetus and neonate on hippocampal synaptic function has been fairly well characterised. Although adult onset hypothyroidism has also been associated with impairments in cognitive function, studies of hippocampal synaptic function with late onset hypothyroidism have yielded inconsistent results. In the present study, we report hypothyroidism induced by the synthesis inhibitor propylthiouracil (10 p.p.m., 0.001%, minimum of 4 weeks), resulted in marginal alterations in excitatory postsynaptic potential (EPSP) and population spike (PS) amplitude in the dentate gyrus measured in vivo. No effects were seen in tests of short-term plasticity, and a minor enhancement of long-term potentiation of the EPSP slope was observed. The most robust synaptic alteration evident in hypothyroid animals was an increase in synaptic response latency, which was paralleled by a failure to maintain normal body temperature under anaesthesia, despite warming on a heating pad. Latency shifts could be reversed in hypothyroid animals by increasing the external heat source and, conversely, synaptic delays could be induced in control animals by removing the heat source, with a consequent drop in body and brain temperature. Thermoregulation is TH- dependent, and anaesthesia necessary for surgical procedures posed a thermoregulatory challenge that was differentially met in control and hypothyroid animals. Minor increases in field potential EPSP slope, decreases in PS amplitudes and increased latencies are consistent with previous reports of hypothermia in naive control rats. We conclude that failures in thyroid-dependent temperature regulation rather than direct action of TH in synaptic physiology are responsible for the observed effects. These findings stand in contrast to the synaptic impairments observed in adult offspring following developmental TH insufficiency, and emphasise the need to control for the potential unintended consequences of hypothermia in the interpretation of hypothyroid-induced changes in physiological systems, most notably synaptic transmission.
authors.affiliation: Departamento de Fisiología 'Mauricio Russek', Escuela Nacional de Ciencias Biológicas, IPN, México City, México; Laboratory of Neurochemistry, National Institute of Pediatrics, Mexico City, Mexico.
authors.forename: K
authors.initials: K
authors.lastname: Sánchez-Huerta
authors.forename: J
authors.initials: J
authors.lastname: Pacheco-Rosado
authors.forename: M E
authors.initials: ME
authors.lastname: Gilbert
mesh_terms: D017668:Age of Onset; D000758:Anesthesia / Q000009:adverse effects*; D000818:Animals; D018891:Dentate Gyrus / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000503:physiopathology*; D007035:Hypothermia / Q000139:chemically induced / Q000503:physiopathology*; D007037:Hypothyroidism / Q000503:physiopathology*; D008297:Male; D011441:Propylthiouracil / Q000008:administration & dosage; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D011441:Propylthiouracil
keywords: adult onset hypothryoidism; hippocampus; hypothermia; propylthiouracil; synaptic transmission; thyroid