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000285351 1001_ $$aOelschlegel, Anja M$$b0
000285351 245__ $$aElevated calneuron-1, an accessory subunit of muscarinic receptors, induces frontotemporal dysconnectivity and schizophrenia-like deficits.
000285351 260__ $$a[Cambridge, Mass.]$$bCell Press$$c2026
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000285351 520__ $$aCalneuron-1 is a Ca2+ sensor that has been linked in several genome-wide association studies to schizophrenia (SCZ). We show that calneuron-1 expression is elevated in the dorsolateral prefrontal cortex of SCZ patients and that overexpression in the medial prefrontal cortex (mPFC) of mice elicits SCZ-related behavioral disabilities, disrupts rhythmogenesis within the mPFC, impairs functional connectivity between the hippocampus and the mPFC, and causes deficits in muscarinic synaptic plasticity. These neurophysiological signatures of SCZ are linked to the role of calneuron-1 as an accessory subunit of muscarinic M1 receptors (M1Rs). Calneuron-1 displaces Gαq11 from the third intracellular loop of M1R at elevated [Ca2+]i, thereby disrupting downstream signaling. The M1R agonist xanomeline, shown to reduce positive and negative symptoms of SCZ and recently approved for clinical use, impedes this calneuron-1/M1R interaction, which leads to restoration of G-protein coupling, muscarinic synaptic plasticity, and network communication. Collectively, our data indicate a potential causative pathomechanism of SCZ.
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000285351 650_7 $$2Other$$aCalneuron-1
000285351 650_7 $$2Other$$amedial prefrontal cortex
000285351 650_7 $$2Other$$amuscarinic M1 receptors
000285351 650_7 $$2Other$$aschizophrenia
000285351 650_7 $$2Other$$axanomeline
000285351 650_7 $$2NLM Chemicals$$aReceptor, Muscarinic M1
000285351 650_7 $$09ORI6L73CJ$$2NLM Chemicals$$axanomeline
000285351 650_7 $$2NLM Chemicals$$aThiadiazoles
000285351 650_7 $$2NLM Chemicals$$aPyridines
000285351 650_2 $$2MeSH$$aAnimals
000285351 650_2 $$2MeSH$$aMice
000285351 650_2 $$2MeSH$$aHumans
000285351 650_2 $$2MeSH$$aSchizophrenia: metabolism
000285351 650_2 $$2MeSH$$aSchizophrenia: genetics
000285351 650_2 $$2MeSH$$aSchizophrenia: physiopathology
000285351 650_2 $$2MeSH$$aReceptor, Muscarinic M1: metabolism
000285351 650_2 $$2MeSH$$aReceptor, Muscarinic M1: agonists
000285351 650_2 $$2MeSH$$aPrefrontal Cortex: metabolism
000285351 650_2 $$2MeSH$$aMale
000285351 650_2 $$2MeSH$$aNeuronal Plasticity: physiology
000285351 650_2 $$2MeSH$$aNeuronal Plasticity: drug effects
000285351 650_2 $$2MeSH$$aFemale
000285351 650_2 $$2MeSH$$aHippocampus: metabolism
000285351 650_2 $$2MeSH$$aHippocampus: physiopathology
000285351 650_2 $$2MeSH$$aMice, Inbred C57BL
000285351 650_2 $$2MeSH$$aThiadiazoles: pharmacology
000285351 650_2 $$2MeSH$$aPyridines
000285351 7001_ $$aPöpplau, Jastyn A$$b1
000285351 7001_ $$aRyzynski, Alexandre$$b2
000285351 7001_ $$aHradsky, Johannes$$b3
000285351 7001_ $$aReddy, Pasham Parameshwar$$b4
000285351 7001_ $$aNavarro, Gemma$$b5
000285351 7001_ $$aReyes-Resina, Irene$$b6
000285351 7001_ $$aYuanxiang, PingAn$$b7
000285351 7001_ $$0P:(DE-2719)2810715$$aSosulina, Liudmila$$b8
000285351 7001_ $$aKaneko, Hiroshi$$b9
000285351 7001_ $$aSahu, Giriraj$$b10
000285351 7001_ $$aGünther, Anne$$b11
000285351 7001_ $$aAndres-Alonso, Maria$$b12
000285351 7001_ $$aLopez-Rojas, Jeffrey$$b13
000285351 7001_ $$aAly, Ahmed A A$$b14
000285351 7001_ $$aBauer, Pavol$$b15
000285351 7001_ $$aMikulovic, Sanja$$b16
000285351 7001_ $$aXia, Zifeng$$b17
000285351 7001_ $$aMikhaylova, Marina$$b18
000285351 7001_ $$0P:(DE-2719)2810375$$aRemy, Stefan$$b19$$udzne
000285351 7001_ $$aHanganu-Opatz, Ileana$$b20
000285351 7001_ $$aKarpova, Anna$$b21
000285351 7001_ $$0P:(DE-2719)2811905$$aKreutz, Michael R$$b22$$eLast author$$udzne
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