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.

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 / A.D. Maio, A. De Rosa, S. Pelucchi, M. Garofalo, B. Marciano, T. Nuzzo, F. Gardoni, A.M. Isidori, M. Di Luca, F. Errico, A. De Bartolomeis, E. Marcello, A. Usiello. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 23:3(2022 Feb), pp. 1539.1-1539.20. [10.3390/ijms23031539]

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

S. Pelucchi;T. Nuzzo;F. Gardoni;M. Di Luca;E. Marcello
;
2022

Abstract

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.
Alzheimer’s disease; Dendritic spine; Parkinson’s disease; Postsynaptic density; Schizophrenia;
Settore BIO/14 - Farmacologia
   Deciphering the role of ADAM10 and CAP2 in Age‐related Accumulation of deficits
   COCOON
   FONDAZIONE CARIPLO
   2018-0511

   Identification and validation of COmmon pathways at the CrOssrOads of neurodegeneration and Neuroprotection (COCOON)
   COCOON
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
   2017MYJ5TH_001

   Dipartimenti di Eccellenza 2018-2022 - Dipartimento di SCIENZE FARMACOLOGICHE E BIOMOLECOLARI
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
feb-2022
28-gen-2022
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/925508
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