AUTHOR=Xian Weiwei , Cao Jingli , Yuan Xiangshan , Wang Guoxiang , Jin Qiuyan , Zhang Hang , Zhou Guomin , You Linya 

TITLE=Deficiency of Intellectual Disability-Related Gene Brpf1 Attenuated Hippocampal Excitatory Synaptic Transmission and Impaired Spatial Learning and Memory Ability

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.711792

DOI=10.3389/fcell.2021.711792

ISSN=2296-634X

ABSTRACT=<p>Patients with monoallelic bromodomain and PHD finger-containing protein 1 (<italic>BRPF1</italic>) mutations showed intellectual disability. The hippocampus has essential roles in learning and memory. Our previous work indicated that <italic>Brpf1</italic> was specifically and strongly expressed in the hippocampus from the perinatal period to adulthood. We hypothesized that mouse <italic>Brpf1</italic> plays critical roles in the morphology and function of hippocampal neurons, and its deficiency leads to learning and memory deficits. To test this, we performed immunofluorescence, whole-cell patch clamp, and mRNA-Seq on shBrpf1-infected primary cultured hippocampal neurons to study the effect of <italic>Brpf1</italic> knockdown on neuronal morphology, electrophysiological characteristics, and gene regulation. In addition, we performed stereotactic injection into adult mouse hippocampus to knock down <italic>Brpf1 in vivo</italic> and examined the learning and memory ability by Morris water maze. We found that mild knockdown of <italic>Brpf1</italic> reduced mEPSC frequency of cultured hippocampal neurons, before any significant changes of dendritic morphology showed. We also found that <italic>Brpf1</italic> mild knockdown in the hippocampus showed a decreasing trend on the spatial learning and memory ability of mice. Finally, mRNA-Seq analyses showed that genes related to learning, memory, and synaptic transmission (such as <italic>C1ql1</italic>, <italic>Gpr17</italic>, <italic>Htr1d</italic>, <italic>Glra1</italic>, <italic>Cxcl10</italic>, and <italic>Grin2a</italic>) were dysregulated upon <italic>Brpf1</italic> knockdown. Our results showed that <italic>Brpf1</italic> mild knockdown attenuated hippocampal excitatory synaptic transmission and reduced spatial learning and memory ability, which helps explain the symptoms of patients with <italic>BRPF1</italic> mutations.</p>