Tau protein is differentially phosphorylated in young- and old-aged rats with experimentally induced hyperthyroidism

Aging involves progressive physiological changes, including thyroid dysfunction; thus, changes in plasma thyroid hormone (TH) level may affect neuronal function such as synaptic plasticity and Tau phosphorylation. However, how Tau protein is modulated in hyperthyroidism with aging is not clear. To clarify this issue, long-term potentiation (LTP) and accompanying phosphorylation of Tau protein in different residues were investigated in the hippocampus of young and old rats with experimentally induced hyperthyroidism. Materials and

Impaired LTP that occurs with aging may be among the underlying causes of dementia in relatively older ages, and l-thyroxine treatment restores this impaired LTP. In addition, the phosphorylation level of Tau epitopes known to play a role in the pathogenesis of Alzheimer's disease may support a critical role in the modulation of synaptic plasticity in hyperthyroidism.

The study was performed in vivo under urethane anesthesia on 2- and 12-month-old Wistar albino male rats. Field potentials, composed of a field of excitatory postsynaptic potential (fEPSP) and a population spike (PS), occurring in the hippocampal dentate gyrus region, were recorded by applying high-frequency stimulation (HFS) to the perforant pathway (100 Hz, four times at 5-min intervals) to induce LTP. Total-Tau and phosphorylated-Tau were measured in HFS-induced hippocampus by using western blotting.

The TH suppressed hippocampal somatic LTP (PS) was suppressed with aging, and treatment improved this suppression in aged rats without any changes in synaptic LTP (fEPSP). The phosphorylation of Tau at Ser202/Thr205 and Thr231 residues was increased in aged control rats. Treatment of aged rats with l-thyroxine reduced the phosphorylation of Tau at these residues to the young control condition.