Ranolazine Attenuates Brain Inflammation in a Rat Model of Type 2 Diabetes

Recent studies suggest a pathogenetic association between metabolic disturbances, including type 2 diabetes (T2DM), and cognitive decline and indicate that T2DM may represent a risk factor for Alzheimer’s disease (AD). There are a number of experimental studies presenting evidence that ranolazine, a...

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Main Authors: Velia Cassano, Martina Tallarico, Giuseppe Armentaro, Caterina De Sarro, Michelangelo Iannone, Antonio Leo, Rita Citraro, Emilio Russo, Giovambattista De Sarro, Marta Letizia Hribal, Angela Sciacqua
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/23/24/16160
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author Velia Cassano
Martina Tallarico
Giuseppe Armentaro
Caterina De Sarro
Michelangelo Iannone
Antonio Leo
Rita Citraro
Emilio Russo
Giovambattista De Sarro
Marta Letizia Hribal
Angela Sciacqua
author_facet Velia Cassano
Martina Tallarico
Giuseppe Armentaro
Caterina De Sarro
Michelangelo Iannone
Antonio Leo
Rita Citraro
Emilio Russo
Giovambattista De Sarro
Marta Letizia Hribal
Angela Sciacqua
author_sort Velia Cassano
collection DOAJ
description Recent studies suggest a pathogenetic association between metabolic disturbances, including type 2 diabetes (T2DM), and cognitive decline and indicate that T2DM may represent a risk factor for Alzheimer’s disease (AD). There are a number of experimental studies presenting evidence that ranolazine, an antianginal drug, acts as a neuroprotective drug. The aim of the present study was to evaluate the effects of ranolazine on hippocampal neurodegeneration and astrocytes activation in a T2DM rat model. Diabetes was induced by a high fat diet (HFD) and streptozotocin (STZ) injection. Animals were divided into the following groups: HFD/STZ + Ranolazine, HFD/STZ + Metformin, HFD/STZ + Vehicle, NCD + Vehicle, NCD + Ranolazine and NCD + Metformin. The presence of neurodegeneration was evaluated in the hippocampal cornus ammonis 1 (CA1) region by cresyl violet staining histological methods, while astrocyte activation was assessed by western blot analysis. Staining with cresyl violet highlighted a decrease in neuronal density and cell volume in the hippocampal CA1 area in diabetic HFD/STZ + Vehicle rats, while ranolazine and metformin both improved T2DM-induced neuronal loss and neuronal damage. Moreover, there was an increased expression of GFAP in the HFD/STZ + Vehicle group compared to the treated diabetic groups. In conclusion, in the present study, we obtained additional evidence supporting the potential use of ranolazine to counteract T2DM-associated cognitive decline.
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spelling doaj.art-40b97bcb182e4554b4545812f082f30a2023-11-24T15:33:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241616010.3390/ijms232416160Ranolazine Attenuates Brain Inflammation in a Rat Model of Type 2 DiabetesVelia Cassano0Martina Tallarico1Giuseppe Armentaro2Caterina De Sarro3Michelangelo Iannone4Antonio Leo5Rita Citraro6Emilio Russo7Giovambattista De Sarro8Marta Letizia Hribal9Angela Sciacqua10Department of Medical and Surgical Sciences, Magna Græcia University, 88100 Catanzaro, ItalyScience of Health Department, Magna Græcia University, 88100 Catanzaro, ItalyDepartment of Medical and Surgical Sciences, Magna Græcia University, 88100 Catanzaro, ItalySystem and Applied Pharmacology@University Magna Grecia, Science of Health Department, School of Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyCNR-Institute for Biomedical Research and Innovation, 88100 Catanzaro, ItalyScience of Health Department, Magna Græcia University, 88100 Catanzaro, ItalyScience of Health Department, Magna Græcia University, 88100 Catanzaro, ItalyScience of Health Department, Magna Græcia University, 88100 Catanzaro, ItalyScience of Health Department, Magna Græcia University, 88100 Catanzaro, ItalyDepartment of Medical and Surgical Sciences, Magna Græcia University, 88100 Catanzaro, ItalyDepartment of Medical and Surgical Sciences, Magna Græcia University, 88100 Catanzaro, ItalyRecent studies suggest a pathogenetic association between metabolic disturbances, including type 2 diabetes (T2DM), and cognitive decline and indicate that T2DM may represent a risk factor for Alzheimer’s disease (AD). There are a number of experimental studies presenting evidence that ranolazine, an antianginal drug, acts as a neuroprotective drug. The aim of the present study was to evaluate the effects of ranolazine on hippocampal neurodegeneration and astrocytes activation in a T2DM rat model. Diabetes was induced by a high fat diet (HFD) and streptozotocin (STZ) injection. Animals were divided into the following groups: HFD/STZ + Ranolazine, HFD/STZ + Metformin, HFD/STZ + Vehicle, NCD + Vehicle, NCD + Ranolazine and NCD + Metformin. The presence of neurodegeneration was evaluated in the hippocampal cornus ammonis 1 (CA1) region by cresyl violet staining histological methods, while astrocyte activation was assessed by western blot analysis. Staining with cresyl violet highlighted a decrease in neuronal density and cell volume in the hippocampal CA1 area in diabetic HFD/STZ + Vehicle rats, while ranolazine and metformin both improved T2DM-induced neuronal loss and neuronal damage. Moreover, there was an increased expression of GFAP in the HFD/STZ + Vehicle group compared to the treated diabetic groups. In conclusion, in the present study, we obtained additional evidence supporting the potential use of ranolazine to counteract T2DM-associated cognitive decline.https://www.mdpi.com/1422-0067/23/24/16160Alzheimer’sneurodegenerationranolazinetype 2 diabetes mellitus
spellingShingle Velia Cassano
Martina Tallarico
Giuseppe Armentaro
Caterina De Sarro
Michelangelo Iannone
Antonio Leo
Rita Citraro
Emilio Russo
Giovambattista De Sarro
Marta Letizia Hribal
Angela Sciacqua
Ranolazine Attenuates Brain Inflammation in a Rat Model of Type 2 Diabetes
International Journal of Molecular Sciences
Alzheimer’s
neurodegeneration
ranolazine
type 2 diabetes mellitus
title Ranolazine Attenuates Brain Inflammation in a Rat Model of Type 2 Diabetes
title_full Ranolazine Attenuates Brain Inflammation in a Rat Model of Type 2 Diabetes
title_fullStr Ranolazine Attenuates Brain Inflammation in a Rat Model of Type 2 Diabetes
title_full_unstemmed Ranolazine Attenuates Brain Inflammation in a Rat Model of Type 2 Diabetes
title_short Ranolazine Attenuates Brain Inflammation in a Rat Model of Type 2 Diabetes
title_sort ranolazine attenuates brain inflammation in a rat model of type 2 diabetes
topic Alzheimer’s
neurodegeneration
ranolazine
type 2 diabetes mellitus
url https://www.mdpi.com/1422-0067/23/24/16160
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