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Adult-onset hyperthyroidism impairs spatial learning: possible involvement of mitogen-activated protein kinase
Soner Bitiktaş1, Başak Kandemir, Burak Tan
1aDepartment 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.
Abstract:
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.
Insights
Hyperthyroidism in adult rats impaired learning acquisition, evidenced by longer escape times in the Morris water maze. This cognitive deficit correlated with increased p38-MAPK phosphorylation in the hippocampus.
Area of Science:
- Neuroscience
- Endocrinology
- Molecular Biology
Background:
- Thyroid hormones influence brain function through genomic and nongenomic pathways.
- Mitogen-activated protein kinase (MAPK) signaling is implicated in nongenomic thyroid hormone actions.
Purpose of the Study:
- To investigate the impact of hyperthyroidism on cognitive function in adult rats.
- To explore the role of p38-MAPK signaling in hyperthyroidism-induced cognitive changes.
Main Methods:
- Adult rats were induced into a hyperthyroid state using L-thyroxine.
- Cognitive performance was assessed using the Morris water maze spatial learning task.
- Hippocampal p38-MAPK, Elk-1, and CREB phosphorylation levels were measured via Western blotting and RT-PCR.
Main Results:
- Hyperthyroid rats exhibited impaired learning acquisition, demonstrated by increased escape latencies and distance moved.
- No significant differences were observed in probe trials, suggesting intact spatial memory retention.
- Hyperthyroidism led to elevated phosphorylated p38-MAPK levels in the hippocampus.
Conclusions:
- Hyperthyroidism in adult rats is associated with deficits in learning acquisition.
- Increased p38-MAPK phosphorylation in the hippocampus may underlie these cognitive impairments.
- Further research is needed to confirm the direct causal link and explore other molecular targets.
