Stimulation of the Hippocampal POMC/MC4R Circuit Alleviates Synaptic Plasticity Impairment in an Alzheimer’s Disease Model
Hippocampal synaptic plasticity is modulated by neuropeptides, the disruption of which might contribute to cognitive deficits observed in Alzheimer’s disease (AD). Although pro-opiomelanocortin (POMC)-derived neuropeptides and melanocortin 4 receptor (MC4R) are implicated in hippocampus-dependent sy...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-11-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716314632 |
| _version_ | 1819106326451585024 |
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| author | Yang Shen Min Tian Yuqiong Zheng Fei Gong Amy K.Y. Fu Nancy Y. Ip |
| author_facet | Yang Shen Min Tian Yuqiong Zheng Fei Gong Amy K.Y. Fu Nancy Y. Ip |
| author_sort | Yang Shen |
| collection | DOAJ |
| description | Hippocampal synaptic plasticity is modulated by neuropeptides, the disruption of which might contribute to cognitive deficits observed in Alzheimer’s disease (AD). Although pro-opiomelanocortin (POMC)-derived neuropeptides and melanocortin 4 receptor (MC4R) are implicated in hippocampus-dependent synaptic plasticity, how the POMC/MC4R system functions in the hippocampus and its role in synaptic dysfunction in AD are largely unknown. Here, we mapped a functional POMC circuit in the mouse hippocampus, wherein POMC neurons in the cornu ammonis 3 (CA3) activate MC4R in the CA1. Suppression of hippocampal MC4R activity in the APP/PS1 transgenic mouse model of AD exacerbates long-term potentiation impairment, which is alleviated by the replenishment of hippocampal POMC/MC4R activity or activation of hippocampal MC4R-coupled Gs signaling. Importantly, MC4R activation rescues amyloid-β-induced synaptic dysfunction via a Gs/cyclic AMP (cAMP)/PKA/cAMP-response element binding protein (CREB)-dependent mechanism. Hence, disruption of this hippocampal POMC/MC4R circuit might contribute to synaptic dysfunction observed in AD, revealing a potential therapeutic target for the disease. |
| first_indexed | 2024-12-22T02:36:22Z |
| format | Article |
| id | doaj.art-1781023c24b9440fa0232ff0b0083e15 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-22T02:36:22Z |
| publishDate | 2016-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-1781023c24b9440fa0232ff0b0083e152022-12-21T18:41:45ZengElsevierCell Reports2211-12472016-11-011771819183110.1016/j.celrep.2016.10.043Stimulation of the Hippocampal POMC/MC4R Circuit Alleviates Synaptic Plasticity Impairment in an Alzheimer’s Disease ModelYang Shen0Min Tian1Yuqiong Zheng2Fei Gong3Amy K.Y. Fu4Nancy Y. Ip5Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, ChinaDivision of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, ChinaDivision of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, ChinaDivision of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, ChinaDivision of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, ChinaDivision of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, ChinaHippocampal synaptic plasticity is modulated by neuropeptides, the disruption of which might contribute to cognitive deficits observed in Alzheimer’s disease (AD). Although pro-opiomelanocortin (POMC)-derived neuropeptides and melanocortin 4 receptor (MC4R) are implicated in hippocampus-dependent synaptic plasticity, how the POMC/MC4R system functions in the hippocampus and its role in synaptic dysfunction in AD are largely unknown. Here, we mapped a functional POMC circuit in the mouse hippocampus, wherein POMC neurons in the cornu ammonis 3 (CA3) activate MC4R in the CA1. Suppression of hippocampal MC4R activity in the APP/PS1 transgenic mouse model of AD exacerbates long-term potentiation impairment, which is alleviated by the replenishment of hippocampal POMC/MC4R activity or activation of hippocampal MC4R-coupled Gs signaling. Importantly, MC4R activation rescues amyloid-β-induced synaptic dysfunction via a Gs/cyclic AMP (cAMP)/PKA/cAMP-response element binding protein (CREB)-dependent mechanism. Hence, disruption of this hippocampal POMC/MC4R circuit might contribute to synaptic dysfunction observed in AD, revealing a potential therapeutic target for the disease.http://www.sciencedirect.com/science/article/pii/S2211124716314632hippocampussynaptic plasticitysynapsesAlzheimer’s diseasememory lossmelanocortin receptorG protein-coupled receptoralpha-melanoctye-stimulating hormonepro-opiomelanocortinneural circuit |
| spellingShingle | Yang Shen Min Tian Yuqiong Zheng Fei Gong Amy K.Y. Fu Nancy Y. Ip Stimulation of the Hippocampal POMC/MC4R Circuit Alleviates Synaptic Plasticity Impairment in an Alzheimer’s Disease Model Cell Reports hippocampus synaptic plasticity synapses Alzheimer’s disease memory loss melanocortin receptor G protein-coupled receptor alpha-melanoctye-stimulating hormone pro-opiomelanocortin neural circuit |
| title | Stimulation of the Hippocampal POMC/MC4R Circuit Alleviates Synaptic Plasticity Impairment in an Alzheimer’s Disease Model |
| title_full | Stimulation of the Hippocampal POMC/MC4R Circuit Alleviates Synaptic Plasticity Impairment in an Alzheimer’s Disease Model |
| title_fullStr | Stimulation of the Hippocampal POMC/MC4R Circuit Alleviates Synaptic Plasticity Impairment in an Alzheimer’s Disease Model |
| title_full_unstemmed | Stimulation of the Hippocampal POMC/MC4R Circuit Alleviates Synaptic Plasticity Impairment in an Alzheimer’s Disease Model |
| title_short | Stimulation of the Hippocampal POMC/MC4R Circuit Alleviates Synaptic Plasticity Impairment in an Alzheimer’s Disease Model |
| title_sort | stimulation of the hippocampal pomc mc4r circuit alleviates synaptic plasticity impairment in an alzheimer s disease model |
| topic | hippocampus synaptic plasticity synapses Alzheimer’s disease memory loss melanocortin receptor G protein-coupled receptor alpha-melanoctye-stimulating hormone pro-opiomelanocortin neural circuit |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716314632 |
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