Phenylketonuria-related synaptic changes in a BTBR-Pah enu2 mouse model

Phenylketonuria is the most common, inherited aminoacidopathy associated with brain injury. To date, no study has focused on the neuropathology of the genetic mouse model of phenylketonuria, BTBR-Pah . We examined dendritic spines and synapses in the CA1 and prefrontal cortex among the wild-type, heterozygous, and BTBR-Pah mice. A reduced density of dendritic spines, a shortened length of the presynaptic active zone, a widened synaptic cleft, and decreased thickness of postsynaptic density were revealed in BTBR-Pah mice. Meanwhile, the phosphorylation at Thr286 of Ca/calmodulin-dependent protein kinase IIα was alerted in BTBR-Pah mice. These findings revealed that phenylketonuria-related brain impairment is accompanied with abnormalities of dendritic spines and synapses. The dysfunction of Ca/calmodulin-dependent protein kinase IIα may result in an impaired synaptic function.