PDIA3 Expression Is Altered in the Limbic Brain Regions of Triple-Transgenic Mouse Model of Alzheimer’s Disease

Tommaso Cassano; Flavia Giamogante; Silvio Calcagnini; Adele Romano; Angelo Michele Lavecchia; Francesca Inglese; Giuliano Paglia; Vidyasagar Naik Bukke; Antonino Davide Romano; Marzia Friuli; Fabio Altieri; Silvana Gaetani

doi:10.3390/ijms24033005

International Journal of Molecular Sciences (Feb 2023)

PDIA3 Expression Is Altered in the Limbic Brain Regions of Triple-Transgenic Mouse Model of Alzheimer’s Disease

Tommaso Cassano,
Flavia Giamogante,
Silvio Calcagnini,
Adele Romano,
Angelo Michele Lavecchia,
Francesca Inglese,
Giuliano Paglia,
Vidyasagar Naik Bukke,
Antonino Davide Romano,
Marzia Friuli,
Fabio Altieri,
Silvana Gaetani

Affiliations

Tommaso Cassano: Department of Medical and Surgical Sciences, University of Foggia, Via L. Pinto 1, 71122 Foggia, Italy
Flavia Giamogante: Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
Silvio Calcagnini: Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
Adele Romano: Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
Angelo Michele Lavecchia: Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
Francesca Inglese: Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
Giuliano Paglia: Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
Vidyasagar Naik Bukke: Department of Medical and Surgical Sciences, University of Foggia, Via L. Pinto 1, 71122 Foggia, Italy
Antonino Davide Romano: Department of Medical and Surgical Sciences, University of Foggia, Via L. Pinto 1, 71122 Foggia, Italy
Marzia Friuli: Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
Fabio Altieri: Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
Silvana Gaetani: Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy

DOI: https://doi.org/10.3390/ijms24033005
Journal volume & issue: Vol. 24, no. 3
p. 3005

Abstract

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In the present study, we used a mouse model of Alzheimer’s disease (AD) (3×Tg-AD mice) to longitudinally analyse the expression level of PDIA3, a protein disulfide isomerase and endoplasmic reticulum (ER) chaperone, in selected brain limbic areas strongly affected by AD-pathology (amygdala, entorhinal cortex, dorsal and ventral hippocampus). Our results suggest that, while in Non-Tg mice PDIA3 levels gradually reduce with aging in all brain regions analyzed, 3×Tg-AD mice showed an age-dependent increase in PDIA3 levels in the amygdala, entorhinal cortex, and ventral hippocampus. A significant reduction of PDIA3 was observed in 3×Tg-AD mice already at 6 months of age, as compared to age-matched Non-Tg mice. A comparative immunohistochemistry analysis performed on 3×Tg-AD mice at 6 (mild AD-like pathology) and 18 (severe AD-like pathology) months of age showed a direct correlation between the cellular level of Aβ and PDIA3 proteins in all the brain regions analysed, even if with different magnitudes. Additionally, an immunohistochemistry analysis showed the presence of PDIA3 in all post-mitotic neurons and astrocytes. Overall, altered PDIA3 levels appear to be age- and/or pathology-dependent, corroborating the ER chaperone’s involvement in AD pathology, and supporting the PDIA3 protein as a potential novel therapeutic target for the treatment of AD.

Published in International Journal of Molecular Sciences

ISSN: 1661-6596 (Print); 1422-0067 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General); Science: Chemistry
Website: http://www.mdpi.com/journal/ijms

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