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Front. Cell. Neurosci. | doi: 10.3389/fncel.2019.00249

Brpf1 haploinsufficiency impairs dendritic arborization and spine formation, leading to cognitive deficits

 Chunjie Zhao1*, Yan Su1, Junhua Liu1, Baocong Yu1 and Ru Ba1
  • 1Southeast University, China

Haploinsufficiency of the bromodomain and PHD finger-containing protein 1 (BRPF1) gene causes intellectual disability (ID), which is characterized by impaired intellectual and cognitive function; however, the neurological basis for ID and the neurological function of BRPF1 dosage in the brain remain unclear. Here, by crossing Emx1-cre mice with Brpf1fl/fl mice, we generated Brpf1 heterozygous mice to model BRPF1-related ID. Brpf1 heterozygotes showed reduced dendritic complexity in both hippocampal granule cells and cortical pyramidal neurons, accompanied by reduced spine density and altered spine and synapse morphology. An in vitro study of Brpf1 haploinsufficiency also demonstrated decreased frequency and amplitude of miniature EPSCs that may subsequently contribute to abnormal behaviors, including decreased anxiety levels and defective learning and memory. Our results demonstrate a critical role for Brpf1 dosage in neuron dendrite arborization, spine morphogenesis and behavior and provide insight into the pathogenesis of BRPF1-related ID.

Keywords: BRPF1, Intellectual Disability, dendrite arborization, Synaptic formation, spine morphogenesis

Received: 25 Mar 2019; Accepted: 17 May 2019.

Edited by:

Josef Bischofberger, Universität Basel, Switzerland

Reviewed by:

Helmut Kessels, Netherlands Institute for Neuroscience (KNAW), Netherlands
Simona Candiani, Department of Earth, Environment and Life Sciences, School of Mathematical, Physical and Natural Sciences, University of Genoa, Italy  

Copyright: © 2019 Zhao, Su, Liu, Yu and Ba. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Chunjie Zhao, Southeast University, Nanjing, China, zhaocj@seu.edu.cn