机构:[1]Department of Neurology, Centre for Neurodegenerative Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, China重点科室诊疗科室神经病学中心首都医科大学附属天坛医院[2]Department of Paediatric Rheumatology and Immunology, Beijing Children’s Hospital, National Centre for Children’s Health, Capital Medical University, Beijing, China临床科室风湿免疫科首都医科大学附属北京儿童医院[3]Department of Breast Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China外科系统(本部)乳腺外科(本部)北京朝阳医院[4]Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China外科系统(本部)泌尿外科(本部)北京朝阳医院[5]Department of Paediatric Neurosurgery, Beijing Children’s Hospital, National Centre for Children’s Health, Capital Medical University, Beijing, China临床科室神经外科首都医科大学附属北京儿童医院[6]Department of Anatomy, School of Basic Medical Sciences, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China[7]School of Medicine, Tsinghua University, Beijing, China
The hippocampus is a structurally and functionally complex brain area that plays important and diverse roles in higher brain functions, such as learning and memory, and mounting evidence indicates that different hippocampal subregions play distinctive roles. The hippocampus is also one of the first regions in the brain to suffer damage in Alzheimer's disease (AD). Synaptic dysfunction in the hippocampus, rather than neuronal loss per se, is paralleled by behavioural and functional deficits in AD. The membrane-associated guanylate kinase (MAGUK) family of proteins, including SAP102, PSD-95, PSD-93 and SAP97, have long been recognized as essential components of the postsynaptic density (PSD) at excitatory synapses. Hippocampal spines are the predominant synaptic transmission sites of excitatory glutamatergic synapses. During postnatal brain development, individual MAGUK members show distinct expression patterns. Although SAP102 has been confirmed as the dominant scaffold protein in neonatal synapses, its expression profiles in adult and ageing rodent hippocampi are discrepant. Furthermore, in AD brains, significantly reduced SAP102 protein levels have been found, suggesting that SAP102 may be related to AD progression; however, the precise mechanism underlying this result remains unclear. Herein, we observed distinct SAP102 expression profiles in the hippocampal CA1, CA3 and DG subregions of rats and APPswe/PS1dE9 (APP/PS1) mice at various ages using immunofluorescence. In Wistar rats, SAP102 was not only highly expressed in the hippocampal subregions of neonatal rats but also maintained relatively high expression levels in adult hippocampi and displayed no obvious decreases in the CA1 and DG subregions of aged rats. Surprisingly, we observed abnormally high SAP102 expression levels in the CA1 stratum moleculare and CA3 stratum polymorphum subregions of 2-month-old APP/PS1 mice, but low SAP102 levels in the DG and CA3 subregions of 7-month-old APP/PS1 mice, reflecting the subregion-specific reactivity and vulnerability of AD mouse models in different disease stages. Our findings provide fundamental data to support the functional differences of SAP102 in different hippocampal subregions during postnatal periods and may serve as the basis for additional functional studies on SAP102 in normal physiological conditions and different stages of AD.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81301100, 81200968, 81771370]; Natural Science Foundation of Beijing MunicipalityBeijing Natural Science Foundation [5152004]; Importation and Development of High-Calibre Talents Project of Beijing Municipal Institutions [CIT TCD 201304175]; Beijing Talents Project [2015002]
第一作者机构:[1]Department of Neurology, Centre for Neurodegenerative Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
通讯作者:
通讯机构:[6]Department of Anatomy, School of Basic Medical Sciences, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China[*1]Department of Anatomy, Capital Medical University, Beijing 100069, China.
推荐引用方式(GB/T 7714):
Dongning Su ,Hui Liu ,Tianrong Liu ,et al.Dynamic SAP102 expression in the hippocampal subregions of rats and APP/PS1 mice of various ages[J].JOURNAL OF ANATOMY.2018,232(6):987-996.doi:10.1111/joa.12807.
APA:
Dongning Su,,Hui Liu,,Tianrong Liu,,Xin Zhang,,Wei Yang,...&Lirong Chang.(2018).Dynamic SAP102 expression in the hippocampal subregions of rats and APP/PS1 mice of various ages.JOURNAL OF ANATOMY,232,(6)
MLA:
Dongning Su,,et al."Dynamic SAP102 expression in the hippocampal subregions of rats and APP/PS1 mice of various ages".JOURNAL OF ANATOMY 232..6(2018):987-996