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JM-20 treatment prevents neuronal damage and memory impairment induced by aluminum chloride in rats

Lookup NU author(s): Professor Tiago OuteiroORCiD

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Abstract

© 2021 Elsevier B.V.The number of people with dementia worldwide is estimated at 50 million by 2018 and continues to rise mainly due to increasing aging and population growth. Clinical impact of current interventions remains modest and all efforts aimed at the identification of new therapeutic approaches are therefore critical. Previously, we showed that JM-20, a dihydropyridine-benzodiazepine hybrid molecule, protected memory processes against scopolamine-induced cholinergic dysfunction. In order to gain further insight into the therapeutic potential of JM-20 on cognitive decline and Alzheimer's disease (AD) pathology, here we evaluated its neuroprotective effects after chronic aluminum chloride (AlCl3) administration to rats and assessed possible alterations in several types of episodic memory and associated pathological mechanisms. Oral administration of aluminum to rodents recapitulates several neuropathological alterations and cognitive impairment, being considered a convenient tool for testing the efficacy of new therapies for dementia. We used behavioral tasks to test spatial, emotional- associative and novel object recognition memory, as well as molecular, enzymatic and histological assays to evaluate selected biochemical parameters. Our study revealed that JM-20 prevented memory decline alongside the inhibition of AlCl3 -induced oxidative stress, increased AChE activity, TNF-α and pro-apoptotic proteins (like Bax, caspase-3, and 8) levels. JM-20 also protected against neuronal damage in the hippocampus and prefrontal cortex. Our findings expanded our understanding of the ability of JM-20 to preserve memory in rats under neurotoxic conditions and confirm its potential capacity to counteract cognitive impairment and etiological factors of AD by breaking the progression of key steps associated with neurodegeneration.

Publication metadata

Author(s): Wong-Guerra M, Montano-Peguero Y, Ramirez-Sanchez J, Jimenez-Martin J, Fonseca-Fonseca LA, Hernandez-Ensenat D, Nonose Y, Valdes O, Mondelo-Rodriguez A, Ortiz-Miranda Y, Bergado G, Carmenate T, Soto del Valle RM, Pardo-Andreu G, Outeiro TF, Padron-Yaquis AS, Martimbianco de Assis A, O Souza D, Nunez-Figueredo Y

Publication type: Article

Publication status: Published

Journal: NeuroToxicology

Year: 2021

Volume: 87

Pages: 70-85

Print publication date: 01/12/2021

Online publication date: 02/09/2021

Acceptance date: 31/08/2021

ISSN (print): 0161-813X

ISSN (electronic): 1872-9711

Publisher: Elsevier B.V.

URL: https://doi.org/10.1016/j.neuro.2021.08.017

DOI: 10.1016/j.neuro.2021.08.017

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