Estradiol has been shown to facilitate synaptic long term potentiation (LTP) mainly through translocation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor from intracellular pool to the post synaptic membrane. On the other hand, oligomeric amyloid beta (oAβ) decreases number of AMPA receptors in the synapses. It is well known that trafficking of AMPA receptors is governed by an atypical and autonomously active isoform of PKC called protein kinase M zeta (PKMζ). In spite of these evidence, the effect of estradiol on PKMζ expression is not yet studied. We aim to examine the possible protective effect of estradiol on PKMζ and AMPA receptor subunits against oAβ in hippocampal primary cell culture. Primary cell culture was prepared from postnatal (P0 to P3) rat pups. They were treated with 1µM OAβ or vehicle for 24 h and then with 100 nM estradiol for another 24 h. The expression level of GluA1, GluA2 and PKMζ were then determined. OAβ decreased the level of GluA1, GluA2 and PKMζ. Estradiol did not change the molecule levels in healthy cells, however, it preserved their expression levels in OAβ treated cells. These findings suggest that estradiol may restore expression level of synapse related molecules in an Alzheimer’ disease cell model, in part, through acting on PKMζ signaling pathway.

Keywords: Alzheimer’s disease, estradiol, PKMζ, amyloid beta, AMPA