Functional impairment of cortical AMPA receptors in schizophrenia

Zeppillo, Tommaso; Schulmann, Anton; Macciardi, Fabìo; Hjelm, Brooke E.; Föcking, Melanie; Sequeira, Pedro; Guella, Ilaria; Cotter, David; Bunney, William E.; Limón, Agenor; Vawter, Marquis P.

doi:10.1016/j.schres.2020.03.037

Cited by 25 publications

(23 citation statements)

References 111 publications

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“…AMPARs have been shown to exhibit a crucial regulatory effect on the synaptic potentiation during LTP and learning and memory (Earnshaw & Bressloff, 2006; Song & Huganir, 2002). It has been demonstrated that the function of cortical AMPARs in schizophrenia was impaired (Zeppillo et al., 2020). Post‐mortem tests also revealed that the expressions of mRNAs encoding GluA1 and GIuA2 were significantly decreased in the hippocampus of schizophrenia patients (Eastwood et al., 1995).…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we hypothesized that fisetin could also be beneficial for the schizophrenia‐associated cognitive and hippocampal synaptic plasticity deficits and we adopted a male rat model of schizophrenia to test this hypothesis. Given that AMPARs (α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptors) mediate the fast excitatory neurotransmission and synaptic plasticity in the central nervous system and a large body of experimental evidence suggests that AMPARs are implicated in schizophrenia (Eastwood et al., 1995; Zeppillo et al., 2020), we thus explored whether regulation of AMPAR function would contribute to the beneficial effects of fisetin on schizophrenia‐associated cognitive impairments.…”

Section: Introductionmentioning

confidence: 99%

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Flavonoid fisetin reverses impaired hippocampal synaptic plasticity and cognitive function by regulating the function of AMPARs in a male rat model of schizophrenia

Zhan

Chen

et al. 2021

Journal of Neurochemistry

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Cognitive deficits are the core feature of schizophrenia and effective treatment strategies are still missing. Previous studies have reported that fisetin promotes long-term potentiation (LTP) and cognitive function in normal rodents and other model animals of neurological diseases. The aim of this study was to assess the effect of fisetin on How to cite this article: Zhan J-Q, Chen C-N, Wu S-X, et al.Flavonoid fisetin reverses impaired hippocampal synaptic plasticity and cognitive function by regulating the function of AMPARs in a male rat model of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Flavonoid fisetin reverses impaired hippocampal synaptic plasticity and cognitive function by regulating the function of AMPARs in a male rat model of schizophrenia

Zhan

Chen

et al. 2021

Journal of Neurochemistry

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“…Taken together, these results are puzzling since it has been demonstrated a pivotal role of this synaptic element in regulating the trafficking of the glutamate AMPA receptors, whose expression, and function have been reported to be altered in SCZ [35]. In this regard, compelling evidence, including genetic-imaging studies, suggests that genetic variants of the DLG1 gene are functionally linked to abnormal cognitive patterns in SCZ patients [36][37][38][39][40].…”

Section: Discussionmentioning

confidence: 99%

Analysis of mRNA and Protein Levels of CAP2, DLG1 and ADAM10 Genes in Post-Mortem Brain of Schizophrenia, Parkinson’s and Alzheimer’s Disease Patients

Maio

Rosa

Pelucchi

et al. 2022

IJMS

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Schizophrenia (SCZ) is a mental illness characterized by aberrant synaptic plasticity and connectivity. A large bulk of evidence suggests genetic and functional links between postsynaptic abnormalities and SCZ. Here, we performed quantitative PCR and Western blotting analysis in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of SCZ patients to investigate the mRNA and protein expression of three key spine shapers: the actin-binding protein cyclase-associated protein 2 (CAP2), the sheddase a disintegrin and metalloproteinase 10 (ADAM10), and the synapse-associated protein 97 (SAP97). Our analysis of the SCZ post-mortem brain indicated increased DLG1 mRNA in DLPFC and decreased CAP2 mRNA in the hippocampus of SCZ patients, compared to non-psychiatric control subjects, while the ADAM10 transcript was unaffected. Conversely, no differences in CAP2, SAP97, and ADAM10 protein levels were detected between SCZ and control individuals in both brain regions. To assess whether DLG1 and CAP2 transcript alterations were selective for SCZ, we also measured their expression in the superior frontal gyrus of patients affected by neurodegenerative disorders, like Parkinson’s and Alzheimer’s disease. Interestingly, also in Parkinson’s disease patients, we found a selective reduction of CAP2 mRNA levels relative to controls but unaltered protein levels. Taken together, we reported for the first time altered CAP2 expression in the brain of patients with psychiatric and neurological disorders, thus suggesting that aberrant expression of this gene may contribute to synaptic dysfunction in these neuropathologies.

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“…The synaptic AMPA receptors and mTOR signaling pathways have been demonstrated to be significantly disrupted in schizophrenia [ 137 , 138 ]. The function of muscarinic system in the modulation of altered synaptic transmission may precipitate or exacerbate certain symptoms of psychiatric disorders.…”

Section: Cholinergic Receptorsmentioning

confidence: 99%

The Role of G Protein-Coupled Receptors (GPCRs) and Calcium Signaling in Schizophrenia. Focus on GPCRs Activated by Neurotransmitters and Chemokines

Boczek

Mackiewicz

Sobolczyk

et al. 2021

Cells

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Schizophrenia is a common debilitating disease characterized by continuous or relapsing episodes of psychosis. Although the molecular mechanisms underlying this psychiatric illness remain incompletely understood, a growing body of clinical, pharmacological, and genetic evidence suggests that G protein-coupled receptors (GPCRs) play a critical role in disease development, progression, and treatment. This pivotal role is further highlighted by the fact that GPCRs are the most common targets for antipsychotic drugs. The GPCRs activation evokes slow synaptic transmission through several downstream pathways, many of them engaging intracellular Ca2+ mobilization. Dysfunctions of the neurotransmitter systems involving the action of GPCRs in the frontal and limbic-related regions are likely to underly the complex picture that includes the whole spectrum of positive and negative schizophrenia symptoms. Therefore, the progress in our understanding of GPCRs function in the control of brain cognitive functions is expected to open new avenues for selective drug development. In this paper, we review and synthesize the recent data regarding the contribution of neurotransmitter-GPCRs signaling to schizophrenia symptomology.

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Functional impairment of cortical AMPA receptors in schizophrenia

Cited by 25 publications

References 111 publications

Flavonoid fisetin reverses impaired hippocampal synaptic plasticity and cognitive function by regulating the function of AMPARs in a male rat model of schizophrenia

Flavonoid fisetin reverses impaired hippocampal synaptic plasticity and cognitive function by regulating the function of AMPARs in a male rat model of schizophrenia

Analysis of mRNA and Protein Levels of CAP2, DLG1 and ADAM10 Genes in Post-Mortem Brain of Schizophrenia, Parkinson’s and Alzheimer’s Disease Patients

The Role of G Protein-Coupled Receptors (GPCRs) and Calcium Signaling in Schizophrenia. Focus on GPCRs Activated by Neurotransmitters and Chemokines

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