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| 1 | Intellectual disability-related chromatin regulator Brpfl affects electrophysiological feature of hippocampal neurons and related pathways显示文摘Intellectual disability(ID)is a prevalent neurodevelopmental disorder,affecting 1%-2%of children.Recent researches revealed that haploinsufficiency of Brpf1 could result in ID.Hippocampus plays important roles in learning and memory which are impaired in people with ID.To study the roles of Brpf1 in hippocampus,we investigated the morphology,electrophysiology and molecular mechanism in both cultured mouse hippocampal neurons by infecting with AAV-shBrpf1 virus and in mouse model by injecting into hippocampal CA1 area with AAV-shBrpf1 virus.The results showed that knockdown of Brpf1(at about 50%)reduced the mEPSC frequency and amplitude of cultured hippocampal neurons,though it had no effects on the morphology of these neurons;reduced expression of Brpf1 also downregulated the mRNA level of Syt4,Grik3 and Neurod6,which involved in neuronal excitability;knockdown of Brpf1 in mouse hippocampal CA1 region led to increased expression of Cxcl10,which was related with the death and apoptosis of hippocampal neurons.Conclusively,our study found that reduced expression of Brpf1 affected the mEPSC frequency and ampltude of hippocampal neurons as well as dysregulate molecular pathways,which shed new light on Brpfl's role in ID. | Xian Weirvei Yuan Xiangshan Cao Jingli Zhou Gruomin You Linya | 2021 | 解剖学杂志2021，44，S01： | 0 |
| 2 | Brpf1 regulates the function of MGE-derived GABAergic interneurons显示文摘Intellectual disability is a broad-spectrum neurodevelopmental disorder characterized by marked impairment of intelligence and adaptive function.Impaired GABA neurotransmission is associated with mental disorders such as epilepsy and mental retardation,and patients with BRPF1 mutations were mentally retarded and often accompanied by epilepsy.Our research is to investigate the role of Brpf1 in the development and function of GABAergic interneurons.We used mouse primary in vitro cultured GABAergic interneurons derived from medial ganglionic eminence(MGE)and utilized AAV-shBrpf1 virus to knockdown Brpf1.The results showed that Brpf1 knockdown led to increased threshold and decreased number of evoked action potentials,and a downward trend of the amplitude and frequency of mIPSC.However,Brpf1 knockdown had lttle effect on the differentiation of GABAergic interneurons as revealed by parvalbumin and somatostatin staining.Moreover,little influence on the morphology was observed as shown by MAP2 and Golgi stain.Finally,it was found that most of the up-regulated genes are involved in protein binding,ubiquitination,and inflammatory response by RNA Seq. | Jingli Cao Weiwei Xian Guomin Zhou Linya You | 2021 | 解剖学杂志2021，44，S01： | 0 |
| 3 | Forebrain excitatory neuron-specific loss of Brpf1 attenuates excitatory synaptic transmission and impairs spatial and fear memory显示文摘Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/7.Brpf1,KAT6A,and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual disability.Our previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain,especially the hippocampus,which has essential roles in learning and memory.Here,we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons,and that its deficiency leads to learning and memory deficits.To test this,we knocked out Brpf1 in forebrain excitatory neurons using CaMKIIa-Cre.We found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1,Slc16a7,Robo3,and Rho,which are related to neural development,synapse function,and memory,thereby damaging spatial and fear memory in mice.These findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation. | Baicheng Zhao Hang Zhang Ying Liu Gaoyu Zu Yuxiao Zhang Jiayi Hu Shuai Liu Linya You | 2024 | Neural Regeneration Research2024，19，5： | 0 |
| 4 | Analysis of cellular diversity and transcriptional regulatory network in human basal ganglia by single cell and bulk RNA sequencing显示文摘The basal ganglia is a critical subcortical nuclei in several parallel and closed circuits,which mainly modulate thalamus-cortex activity.Dysfunction in any one of these loops connecting cortex can lead to movement and/or mood disorders.To understand cellular complexity,differential gene expression and transcriptional regulatory network of human basal ganglia under normal condition,we performed single cell RNA sequencing of 2424 cells sampled from the basal ganglia of human postmortem brains including caudate,putamen,substantia nigra and globus pallidus. | Li Fengjiao Mohammadi H.B.Asad Yuan Xiangshan Xian Weiwei Liu Qiong Li Wensheng Zhou Guomin Wang Edwin You Linya | 2021 | 解剖学杂志2021，44，S01： | 0 |
| 5 | Understandingnormal and diseased human basal ganglia using combinatory indexing single nuclei RNA sequencing显示文摘With the advent of single cell technology and its rapid applications in the biomedical field,it becomes possible to identify,categorize and characterize each single cell in the brain.Shanghai Brain Bank is accumulating donorbrains very fast(estimately 80 brains till now)from people with normal aging or various neurodegenerative diseases.The basal ganglia is critical for movement control,behavior,cognition,emotion and reward.Many neurodegenerative diseases are related to the abnormality or aging of human basal ganglia.Single nuclei transcriptomic profiles of both normal and diseased human basal ganglia are still sparse.In our study,we systematically examined different nuclei(caudate,putamen,globus pallidus,and substantia nigra)in human basal ganglia from 6 control and 5 diseased donors(2 psychiatric diseases,2 PD and 1 AD)using combinatory indexing single nuclei RNA sequencing.Gene expression was measured on a total of 22309 control and 42590 diseased single cells. | Li Fengjiao Li Peilong Yuan Xiangshan Xian Weiwei Liu Qiong Li Wensheng Zhu Ying You Linya | 2021 | 解剖学杂志2021，44，S01： | 0 |
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