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Phenylketonuria-related synaptic changes in a BTBR-Pahenu2 mouse model

Liang, Lili; Gu, Xuefan; Lu, Lihua; Li, Duan; Zhang, Xinshun

doi: 10.1097/WNR.0b013e3283495acc

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-Pahenu2. We examined dendritic spines and synapses in the CA1 and prefrontal cortex among the wild-type, heterozygous, and BTBR-Pahenu2 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-Pahenu2 mice. Meanwhile, the phosphorylation at Thr286 of Ca2+/calmodulin-dependent protein kinase IIα was alerted in BTBR-Pahenu2 mice. These findings revealed that phenylketonuria-related brain impairment is accompanied with abnormalities of dendritic spines and synapses. The dysfunction of Ca2+/calmodulin-dependent protein kinase IIα may result in an impaired synaptic function.

Department of Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai, China

Correspondence to Dr Xuefan Gu, Xinhua Hospital, 1665 Kongjiang Road, Shanghai 200092, China Tel: +86 21 65011012; fax: +86 21 65791316; e-mail:

Received April 18, 2011

Accepted May 30, 2011

© 2011 Lippincott Williams & Wilkins, Inc.