+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Stimulation of the Hippocampal POMC/MC4R Circuit Alleviates Synaptic Plasticity Impairment in an Alzheimer's Disease Model

Stimulation of the Hippocampal POMC/MC4R Circuit Alleviates Synaptic Plasticity Impairment in an Alzheimer's Disease Model

Cell Reports 17(7): 1819-1831

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.

(PDF emailed within 0-6 h: $19.90)

Accession: 058905979

Download citation: RISBibTeXText

PMID: 27829153

DOI: 10.1016/j.celrep.2016.10.043

Related references

Age-dependent impairment of spine morphology and synaptic plasticity in hippocampal CA1 neurons of a presenilin 1 transgenic mouse model of Alzheimer's disease. Journal of Neuroscience 29(32): 10144-10152, 2009

Chronic estrogen treatment alleviates an impairment in hippocampal synaptic plasticity following bilateral ovariectomy in rats. Society for Neuroscience Abstracts 26(1-2): Abstract No -651 14, 2000

Impairment of adolescent hippocampal plasticity in a mouse model for Alzheimer's disease precedes disease phenotype. Plos One 3(7): E2759, 2008

Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease. Plos One 5(9), 2011

Memory formation and hippocampal synaptic plasticity is reversibly enhanced and impairedin an APP/PS-1 mouse model of Alzheimer's disease. 2007

Chronic psychosocial stress exacerbates impairment of synaptic plasticity in β-amyloid rat model of Alzheimer's disease: prevention by nicotine. Current Alzheimer Research 8(7): 718-731, 2012

Effect of troxerutin on synaptic plasticity of hippocampal dentate gyrus neurons in a β-amyloid model of Alzheimer׳s disease: an electrophysiological study. European Journal of Pharmacology 732: 19-25, 2014

Concomitant histone deacetylase and phosphodiesterase 5 inhibition synergistically prevents the disruption in synaptic plasticity and it reverses cognitive impairment in a mouse model of Alzheimer's disease. Clinical Epigenetics 7: 108, 2015

Low-Frequency Repetitive Transcranial Magnetic Stimulation Ameliorates Cognitive Function and Synaptic Plasticity in APP23/PS45 Mouse Model of Alzheimer's Disease. Frontiers in Aging Neuroscience 9: 292, 2017

Low-Frequency Electrical Stimulation Reduces the Impairment in Synaptic Plasticity Following Epileptiform Activity in Rat Hippocampal Slices through α 1 , But Not α 2 , Adrenergic Receptors. Neuroscience 2019, 2019

Hippocampal synaptic plasticity in Alzheimer's disease: what have we learned so far from transgenic models?. Reviews in the Neurosciences 22(4): 373-402, 2011

Postnatal systemic inflammation exacerbates impairment of hippocampal synaptic plasticity in an animal seizure model. Neuroimmunomodulation 20(4): 223-232, 2014

Synaptic plasticity and functional stabilization in the hippocampal formation: possible role in Alzheimer's disease. Advances in Neurology 47: 313-335, 1988

TGF-β1 Restores Hippocampal Synaptic Plasticity and Memory in Alzheimer Model via the PI3K/Akt/Wnt/β-Catenin Signaling Pathway. Journal of Molecular Neuroscience 2018, 2018

Neurotoxicity and synaptic plasticity impairment of N-acetylglucosamine polymers: implications for Alzheimer's disease. Neurobiology of Aging 36(5): 1780-1791, 2016