Glutamate-induced rapid induction of Arc/Arg3.1 requires NMDA receptor-mediated phosphorylation of ERK and CREB

Publication date: 20 November 2017 Source:Neuroscience Letters, Volume 661 Author(s): Tao Chen, Jie Zhu, Li-Kun Yang, Yi Feng, Wei Lin, Yu-Hai Wang Arc/Arg3.1 is a unique immediate early gene whose expression is highly dynamic and correlated with various forms of synaptic plasticity. Many previous reports highlight the complexity of mechanisms that regulate Arc/Arg3.1 expression in neurons. In the present study, the expression and regulation of Arc/Arg3.1 after glutamate treatment in primary cultured cortical neurons were investigated. We found that both Arc/Arg3.1 mRNA and Arc/Arg3.1 protein dynamically increased within 24h after glutamate treatment. The results of immunostaining showed that abundant amounts of Arc/Arg3.1 protein are presented in both soma and dendrites. The glutamate-induced increase in Arc/Arg3.1 protein levels was partially prevented by the NMDAR inhibitor DL-AP5, but not the AMPAR inhibitor NBQX. The results of calcium imaging showed that glutamate induced significant increases in intracellular calcium levels in a NMDAR-dependent manner. However, the intracellular calcium chelator BAPTA-AM had no effect on glutamate-induced upregulation of Arc/Arg3.1 protein, and alteration of cytosolic calcium ion homeostasis with A23187 and TG did not change Arc/Arg3.1 protein levels. In addition, the phosphorylation of ERK and CREB, two downstream factors of NMDAR signaling, markedly increased after glutamate exposure. Blocking ERK and CREB activation via sele...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research