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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

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 pre...

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Autores principales: Di Maio, Anna, De Rosa, Arianna, Pelucchi, Silvia, Garofalo, Martina, Marciano, Benedetta, Nuzzo, Tommaso, Gardoni, Fabrizio, Isidori, Andrea M., Di Luca, Monica, Errico, Francesco, De Bartolomeis, Andrea, Marcello, Elena, Usiello, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835961/
https://www.ncbi.nlm.nih.gov/pubmed/35163460
http://dx.doi.org/10.3390/ijms23031539
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author Di Maio, Anna
De Rosa, Arianna
Pelucchi, Silvia
Garofalo, Martina
Marciano, Benedetta
Nuzzo, Tommaso
Gardoni, Fabrizio
Isidori, Andrea M.
Di Luca, Monica
Errico, Francesco
De Bartolomeis, Andrea
Marcello, Elena
Usiello, Alessandro
author_facet Di Maio, Anna
De Rosa, Arianna
Pelucchi, Silvia
Garofalo, Martina
Marciano, Benedetta
Nuzzo, Tommaso
Gardoni, Fabrizio
Isidori, Andrea M.
Di Luca, Monica
Errico, Francesco
De Bartolomeis, Andrea
Marcello, Elena
Usiello, Alessandro
author_sort Di Maio, Anna
collection PubMed
description 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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spelling pubmed-88359612022-02-12 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 Di Maio, Anna De Rosa, Arianna Pelucchi, Silvia Garofalo, Martina Marciano, Benedetta Nuzzo, Tommaso Gardoni, Fabrizio Isidori, Andrea M. Di Luca, Monica Errico, Francesco De Bartolomeis, Andrea Marcello, Elena Usiello, Alessandro Int J Mol Sci Article 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. MDPI 2022-01-28 /pmc/articles/PMC8835961/ /pubmed/35163460 http://dx.doi.org/10.3390/ijms23031539 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Di Maio, Anna
De Rosa, Arianna
Pelucchi, Silvia
Garofalo, Martina
Marciano, Benedetta
Nuzzo, Tommaso
Gardoni, Fabrizio
Isidori, Andrea M.
Di Luca, Monica
Errico, Francesco
De Bartolomeis, Andrea
Marcello, Elena
Usiello, Alessandro
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835961/
https://www.ncbi.nlm.nih.gov/pubmed/35163460
http://dx.doi.org/10.3390/ijms23031539
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