Adult-onset hyperthyroidism impairs spatial learning: possible involvement of mitogen-activated protein kinase signaling pathways.
Given evidence that mitogen-activated protein kinase (MAPK) activation is part of the nongenomic actions of thyroid hormones, we investigated the possible consequences of hyperthyroidism for the cognitive functioning of adult rats. Young adult rats were treated with L-thyroxine or saline. Twenty rats in each group were exposed to Morris water maze testing, measuring their performance in a hidden-platform spatial task. In a separate set of rats not exposed to Morris water maze testing (untrained rats), the expression and phosphorylated levels of p38-MAPK and of its two downstream effectors, Elk-1 and cAMP response element-binding protein, were evaluated using quantitative reverse transcriptase-PCR and western blotting. Rats with hyperthyroidism showed delayed acquisition of learning compared with their wild-type counterparts, as shown by increased escape latencies and distance moved on the last two trials of daily training in the water maze. The hyperthyroid rats, however, showed no difference during probe trials. Western blot analyses of the hippocampus showed that hyperthyroidism increased phosphorylated p38-MAPK levels in untrained rats. Although our study is correlative in nature and does not exclude the contribution of other molecular targets, our findings suggest that the observed impairments in acquisition during actual learning in rats with hyperthyroidism may result from the increased phosphorylation of p38-MAPK.
aDepartment of Physiology, Faculty of Medicine bDepartment of Histology and Embryology, Faculty of Veterinary cDepartment of Medical Biology, Faculty of Medicine, Erciyes University, Kayseri dDepartment of Genetics and Bioengineering, Yeditepe University, Istanbul eMolecular Neurobiology Laboratory (AxanLab), Department of Molecular Biology and Genetics, Gebze Technical University, Kocaeli, Turkey.
Soner
S
Bitiktaş
Başak
B
Kandemir
Burak
B
Tan
Şehrazat
Ş
Kavraal
Narin
N
Liman
Nurcan
N
Dursun
Hamiyet
H
Dönmez-Altuntaş
Işil
I
Aksan-Kurnaz
Cem
C
Suer
D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D006980:Hyperthyroidism / Q000150:complications* / Q000473:pathology; D007859:Learning Disabilities / Q000209:etiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D018782:Maze Learning; D011939:Mental Recall / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D065853:Spatial Learning / Q000502:physiology*; D013974:Thyroxine / Q000633:toxicity; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D050882:CREB-Binding Protein; D048051:p38 Mitogen-Activated Protein Kinases; D013974:Thyroxine