title: Effects of thyroxine treatment on histology and behavior using the methimazole model of congenital hypothyroidism in the rat.
abstract: The timing of thyroxine (T4) replacement treatment in congenital hypothyroidism (CH) has been suggested to be important for optimizing cognitive recovery in humans; however this has not been fully established using modern animal models of CH. Consequently, the current studies investigated the ameliorating effects of postnatal T4 treatment on neuropathology and behavior in CH rats. Rat dams were administered methimazole to produce CH offspring, then brain tissue from male CH pups was analyzed to determine the effects of postnatal (P3, P7, P14 and P21) T4 treatment on hippocampal dendritic branching and the expression of nerve growth factor (NGF). Two operant behavioral procedures were employed to confirm and extend previous findings obtained using this model, and to investigate timelines for instigating T4 treatment on improved behavioral outcomes. T4 treatment initiated at P14 was protective of a reduction in dendritic branching in the hippocampus, and initiated at P7 was protective of a reduction of NGF expression in the fimbria of the hippocampus. Induction of CH did not affect the acquisition of simple operant response rules but had a significant effect on the acquisition of complex operant rules subsequently imposed. Furthermore, T4 treatment initiated at P3 protected learning deficits seen following the imposition of complex operant response rules. These findings indicate T4 treatment initiated at P7 is sufficient for the protection of hippocampal NGF expression and dendritic branching but for the protection of complex behavioral abilities T4 treatment is necessary prior to or approximating P3.
authors.affiliation: School of Psychology, Queens University, University Road, Belfast BT7 1NN, Northern Ireland, UK. Electronic address: e.ohare@qub.ac.uk.
authors.forename: E
authors.initials: E
authors.lastname: O'Hare
authors.affiliation: School of Psychology, University of Ulster, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK. Electronic address: e.kim@ulster.ac.uk.
authors.forename: E-M
authors.initials: EM
authors.lastname: Kim
authors.affiliation: School of Psychology, Queens University, University Road, Belfast BT7 1NN, Northern Ireland, UK. Electronic address: d.page@qub.ac.uk.
authors.forename: D
authors.initials: D
authors.lastname: Page
authors.affiliation: Dublin Business School, Angier Street, Dublin 2, Ireland. Electronic address: rosie.reid@dbs.ie.
authors.forename: R
authors.initials: R
authors.lastname: Reid
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D003409:Congenital Hypothyroidism / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003712:Dendrites / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D020249:Hormone Replacement Therapy / Q000379:methods*; D008297:Male; D008713:Methimazole; D020932:Nerve Growth Factor / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013974:Thyroxine / Q000008:administration & dosage*
chemical_list: D008713:Methimazole; D020932:Nerve Growth Factor; D013974:Thyroxine
keywords: congenital hypothyroidism; dendritic branching; nerve growth factor; operant behavior; rat model; thyroxine