Seizure-Induced Regulations of Amyloid-β, STEP₆₁, and STEP₆₁ Substrates Involved in Hippocampal Synaptic Plasticity

Figure 6

Model by which seizure-induced changes in Aβ, STEP₆₁, and Tyr-phosphorylation of STEP₆₁ lead to synaptic weakening in the hippocampus. A single ECS increases STEP₆₁ expression and decreases Tyr-phosphorylation of NMDAR subunit GluN2B and ERK1/2 in the hippocampus at 48 h time point, leading to synaptic weakening via NMDAR internalization and ERK1/2 inactivation. A delayed decrease in ERK1/2 expression as well as a delayed enhancement of APP and Aβ expression at 72–96 h following a single ECS maintains this synaptic weakening. Chronic ECS-induced increase in APP expression and Aβ production as well as persistent decrease in total GluN2B level leads to synaptic weakening.