Disrupted presynaptic nectin1-based neuronal adhesion in the entorhinal-hippocampal circuit contributes to early-life stress-induced memory deficits
Abstract The cell adhesion molecule nectin3 and its presynaptic partner nectin1 have been linked to early-life stress-related cognitive disorders, but how the nectin1-nectin3 system contributes to stress-induced neuronal, circuit, and cognitive abnormalities remains to be studied. Here we show that...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-04-01
|
| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-022-01908-y |
| _version_ | 1819061153021558784 |
|---|---|
| author | Chen Wu Qian Gong Xue Xu Ping Fang Chi Wang Jing-Ying Yu Xing-Xing Wang San-Hua Fang Wen-Juan Chen Hui-Fang Lou Yu-Hui Liu Liang Wang Yi-Jun Liu Wei Chen Xiao-Dong Wang |
| author_facet | Chen Wu Qian Gong Xue Xu Ping Fang Chi Wang Jing-Ying Yu Xing-Xing Wang San-Hua Fang Wen-Juan Chen Hui-Fang Lou Yu-Hui Liu Liang Wang Yi-Jun Liu Wei Chen Xiao-Dong Wang |
| author_sort | Chen Wu |
| collection | DOAJ |
| description | Abstract The cell adhesion molecule nectin3 and its presynaptic partner nectin1 have been linked to early-life stress-related cognitive disorders, but how the nectin1-nectin3 system contributes to stress-induced neuronal, circuit, and cognitive abnormalities remains to be studied. Here we show that in neonatally stressed male mice, temporal order and spatial working memories, which require the medial entorhinal cortex (MEC)-CA1 pathway, as well as the structural integrity of CA1 pyramidal neurons were markedly impaired in adulthood. These cognitive and structural abnormalities in stressed mice were associated with decreased nectin levels in entorhinal and hippocampal subregions, especially reduced nectin1 level in the MEC and nectin3 level in the CA1. Postnatal suppression of nectin1 but not nectin3 level in the MEC impaired spatial memory, whereas conditional inactivation of nectin1 from MEC excitatory neurons reproduced the adverse effects of early-life stress on MEC-dependent memories and neuronal plasticity in CA1. Our data suggest that early-life stress disrupts presynaptic nectin1-mediated interneuronal adhesion in the MEC-CA1 pathway, which may in turn contribute to stress-induced synaptic and cognitive deficits. |
| first_indexed | 2024-12-21T14:38:21Z |
| format | Article |
| id | doaj.art-43757870b5a4421798066c90457c2e95 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-12-21T14:38:21Z |
| publishDate | 2022-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-43757870b5a4421798066c90457c2e952022-12-21T19:00:16ZengNature Publishing GroupTranslational Psychiatry2158-31882022-04-0112111310.1038/s41398-022-01908-yDisrupted presynaptic nectin1-based neuronal adhesion in the entorhinal-hippocampal circuit contributes to early-life stress-induced memory deficitsChen Wu0Qian Gong1Xue Xu2Ping Fang3Chi Wang4Jing-Ying Yu5Xing-Xing Wang6San-Hua Fang7Wen-Juan Chen8Hui-Fang Lou9Yu-Hui Liu10Liang Wang11Yi-Jun Liu12Wei Chen13Xiao-Dong Wang14Department of Neurobiology and Department of Psychiatry of Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Neurobiology and Department of Psychiatry of Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Neurobiology and Department of Psychiatry of Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Neurobiology and Department of Psychiatry of Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Neurobiology and Department of Psychiatry of Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Neurobiology and Department of Psychiatry of Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Anesthesiology, Technische Universität München/Klinikum Rechts der IsarDepartment of Neurobiology and Department of Psychiatry of Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Neurobiology and Department of Psychiatry of Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Neurobiology and Department of Psychiatry of Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Neurobiology and Department of Psychiatry of Sir Run Run Shaw Hospital, Zhejiang University School of MedicineNHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang UniversityDepartment of Neurobiology and Department of Psychiatry of Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Neurobiology and Department of Psychiatry of Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Neurobiology and Department of Psychiatry of Sir Run Run Shaw Hospital, Zhejiang University School of MedicineAbstract The cell adhesion molecule nectin3 and its presynaptic partner nectin1 have been linked to early-life stress-related cognitive disorders, but how the nectin1-nectin3 system contributes to stress-induced neuronal, circuit, and cognitive abnormalities remains to be studied. Here we show that in neonatally stressed male mice, temporal order and spatial working memories, which require the medial entorhinal cortex (MEC)-CA1 pathway, as well as the structural integrity of CA1 pyramidal neurons were markedly impaired in adulthood. These cognitive and structural abnormalities in stressed mice were associated with decreased nectin levels in entorhinal and hippocampal subregions, especially reduced nectin1 level in the MEC and nectin3 level in the CA1. Postnatal suppression of nectin1 but not nectin3 level in the MEC impaired spatial memory, whereas conditional inactivation of nectin1 from MEC excitatory neurons reproduced the adverse effects of early-life stress on MEC-dependent memories and neuronal plasticity in CA1. Our data suggest that early-life stress disrupts presynaptic nectin1-mediated interneuronal adhesion in the MEC-CA1 pathway, which may in turn contribute to stress-induced synaptic and cognitive deficits.https://doi.org/10.1038/s41398-022-01908-y |
| spellingShingle | Chen Wu Qian Gong Xue Xu Ping Fang Chi Wang Jing-Ying Yu Xing-Xing Wang San-Hua Fang Wen-Juan Chen Hui-Fang Lou Yu-Hui Liu Liang Wang Yi-Jun Liu Wei Chen Xiao-Dong Wang Disrupted presynaptic nectin1-based neuronal adhesion in the entorhinal-hippocampal circuit contributes to early-life stress-induced memory deficits Translational Psychiatry |
| title | Disrupted presynaptic nectin1-based neuronal adhesion in the entorhinal-hippocampal circuit contributes to early-life stress-induced memory deficits |
| title_full | Disrupted presynaptic nectin1-based neuronal adhesion in the entorhinal-hippocampal circuit contributes to early-life stress-induced memory deficits |
| title_fullStr | Disrupted presynaptic nectin1-based neuronal adhesion in the entorhinal-hippocampal circuit contributes to early-life stress-induced memory deficits |
| title_full_unstemmed | Disrupted presynaptic nectin1-based neuronal adhesion in the entorhinal-hippocampal circuit contributes to early-life stress-induced memory deficits |
| title_short | Disrupted presynaptic nectin1-based neuronal adhesion in the entorhinal-hippocampal circuit contributes to early-life stress-induced memory deficits |
| title_sort | disrupted presynaptic nectin1 based neuronal adhesion in the entorhinal hippocampal circuit contributes to early life stress induced memory deficits |
| url | https://doi.org/10.1038/s41398-022-01908-y |
| work_keys_str_mv | AT chenwu disruptedpresynapticnectin1basedneuronaladhesionintheentorhinalhippocampalcircuitcontributestoearlylifestressinducedmemorydeficits AT qiangong disruptedpresynapticnectin1basedneuronaladhesionintheentorhinalhippocampalcircuitcontributestoearlylifestressinducedmemorydeficits AT xuexu disruptedpresynapticnectin1basedneuronaladhesionintheentorhinalhippocampalcircuitcontributestoearlylifestressinducedmemorydeficits AT pingfang disruptedpresynapticnectin1basedneuronaladhesionintheentorhinalhippocampalcircuitcontributestoearlylifestressinducedmemorydeficits AT chiwang disruptedpresynapticnectin1basedneuronaladhesionintheentorhinalhippocampalcircuitcontributestoearlylifestressinducedmemorydeficits AT jingyingyu disruptedpresynapticnectin1basedneuronaladhesionintheentorhinalhippocampalcircuitcontributestoearlylifestressinducedmemorydeficits AT xingxingwang disruptedpresynapticnectin1basedneuronaladhesionintheentorhinalhippocampalcircuitcontributestoearlylifestressinducedmemorydeficits AT sanhuafang disruptedpresynapticnectin1basedneuronaladhesionintheentorhinalhippocampalcircuitcontributestoearlylifestressinducedmemorydeficits AT wenjuanchen disruptedpresynapticnectin1basedneuronaladhesionintheentorhinalhippocampalcircuitcontributestoearlylifestressinducedmemorydeficits AT huifanglou disruptedpresynapticnectin1basedneuronaladhesionintheentorhinalhippocampalcircuitcontributestoearlylifestressinducedmemorydeficits AT yuhuiliu disruptedpresynapticnectin1basedneuronaladhesionintheentorhinalhippocampalcircuitcontributestoearlylifestressinducedmemorydeficits AT liangwang disruptedpresynapticnectin1basedneuronaladhesionintheentorhinalhippocampalcircuitcontributestoearlylifestressinducedmemorydeficits AT yijunliu disruptedpresynapticnectin1basedneuronaladhesionintheentorhinalhippocampalcircuitcontributestoearlylifestressinducedmemorydeficits AT weichen disruptedpresynapticnectin1basedneuronaladhesionintheentorhinalhippocampalcircuitcontributestoearlylifestressinducedmemorydeficits AT xiaodongwang disruptedpresynapticnectin1basedneuronaladhesionintheentorhinalhippocampalcircuitcontributestoearlylifestressinducedmemorydeficits |