JCI GluN2B suppression restores phenylalanine-induced neuroplasticity and cognition impairments in a mouse model of phenylketonuria

JCI GluN2B suppression restores phenylalanine-induced neuroplasticity and cognition impairments in a mouse model of phenylketonuria

Phenylketonuria (PKU), an inborn error of phenylalanine (Phe) metabolism, is a common cause of intellectual disability. However, the mechanisms by which elevated Phe levels cause cognitive impairment remain unclear. Here, we show that submillimolar Phe perturbs synaptic plasticity through the hyperactivation of GluN2B-containing NMDARs. PahEnu2 PKU model mice exhibited submillimolar and supramillimolar concentrations of Phe in the cerebrospinal …