The loss of dopaminergic neurons in DEC1 deficient mice potentially involves the decrease of PI3K/Akt/GSK3ß signaling

Abstract

Here we study the effects of differentiated embryonic chondrocyte gene 1(DEC1) deficiency on midbrain dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) through behavioral, histological and molecular analysis. We have found that compared to the age-matched WT mice, DEC1 deficient mice show a decrease in locomotor activity and motor coordination, which shows the main features of Parkinson's disease (PD). But there is no significant difference in spatial learning and memory skills between WT and DEC1 KO mice. Compared to the age-matched WT mice, DEC1 deficient mice exhibit the loss of DA neurons in the SNpc and reduction of dopamine and its metabolites in the striatum. The activated caspase-3 and TH/TUNEL+ cells increase in the SNpc of 6- and 12-month-old DEC1 KO mice compared to those of the age-matched WT mice. But we haven't found any NeuN/TUNEL+ cell increase in the hippocampus of the above two types of mice at the age of 6 months. Furthermore, DEC1 deficiency leads to a significant inhibition of PI3K/Akt/GSK3ß signaling pathway. Additionally, LiCl could rescue the DA neuron loss of midbrain in the 6-month-old DEC1 KO mice. Taken together, the loss of DA neurons in the DEC1 deficient mice potentially involves the downregulation of PI3K/Akt/GSK3ß signaling.