JM-20 protects memory acquisition and consolidation on scopolamine model of cognitive impairment

Wong-Guerra, Maylin; Jimenez-Martin, Javier; Fonseca-Fonseca, Luis Arturo; Ramírez-Sánchez, Jeney; Montano-Peguero, Yanay; Rocha, João Batista Teixeira da; Avila, Fernanda D; Assis, Adriano Martimbianco de; Souza, Diogo O.; Pardo-Andreu, Gilberto L.; Valle, Roberto Menéndez-Soto del; Lopez, Guillermo Aparicio; Martínez, Odalys Valdés; García, Nelson Merino; Mondelo-Rodriguez, Abel; Padrón-Yaquis, Alejandro Saúl; Nuñez-Figueredo, Yanier

doi:10.1080/01616412.2019.1573285

Cited by 13 publications

(11 citation statements)

References 40 publications

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“…JM-20 co-administration after 15 days of AlCl 3 treatments, until day 30, reversed aluminum induced memory de cits, which indicate its memory protecting effect. Our previous work denotes that JM-20 reversed the memory de cits induced by scopolamine, an indication of cognitive protection mediated by this molecule, but in a transient model of dementia, useful to detect JM-20 activity against a very fast cholinergic dysfunction (thirty minutes after injection) [16]. In the present study, JM-20 also showed a protective effect but against chronic aluminum exposure, more similar to clinical conditions.…”

Section: Discussionsupporting

confidence: 76%

“…It is noteworthy that JM-20 has inherent anti-AChE activity properties. Previously we have demonstrated using in vitro and in silico studies that JM-20 has a strong AChE inhibitory activity (IC 50 ≈ 200 nM) [16,65].…”

Section: Discussionmentioning

confidence: 99%

“…The absorbance was read at 412 nm during 20 min at 1 min interval. The AChE activity was expressed as μmol of (ATCh) iodide hydrolyzed per min per mg protein [16,32].…”

Section: Acetylcholinesterase Activity On Brain Homogenatementioning

confidence: 99%

“…The mitochondrial membrane potential (ΔΨ) was determined spectro uorimetrically using safranine O (10 μM) as a probe at 495/586 nm excitation/emission wavelengths. These assays were performed in the presence of EGTA (0.1 mM) and K 2 HPO 4 (2 mM) [11,16,32]. Mitochondrial swelling.…”

Section: Mitochondrial Assaysmentioning

confidence: 99%

“…In addition, other pharmacological effects were detected as direct or indirect action of JM-20 in the complex scenery of the pathological models of AD. Oral administration of JM-20 prevents memory impairment, in episodic memory and in acquisition-consolidation processes against acute scopolamine treatment [16]. Drawing from all these positive antecedents, we hypothesized that this molecule could revert and prevent neurotoxic chronic damage that involves more complex long-term mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Multifunctional Molecule, JM-20, Reverses Aluminum Chloride-Induced Memory Impairment and Neuronal Damage in Rats

Wong-Guerra

Montano-Peguero

Ramírez-Sánchez

et al. 2021

Preprint

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Alzheimer's disease (AD) is a neurodegenerative disease that worsens with aging. Today, there is a worldwide effort to find new drugs that could delay the onset, slow the progression, or improve symptoms of AD. Oral administration of aluminum to rodents recapitulates some pathological alterations observed in AD, being considered a convenient tool for modeling and testing the efficacy of new therapeutics. Our previous studies have shown that JM-20, a dihydropyridine and benzodiazepine hybrid molecule protected memory in an environment with cholinergic dysfunction, high oxidative stress, hyperactivation of acetylcholinesterase (AChE) enzyme, and mitochondrial damage produced by scopolamine. In order to gain further insight into the effects on JM-20 on AD pathology, we evaluated the protective effects of JM-20 after chronic AlCl3 administration to rats, and assessed several types of episodic memory alterations and associated-pathological mechanisms, including mitochondrial dysfunction, AChE hyperactivity, inflammation, and apoptosis-related proteins. We used behavioral tasks to test spatial, working an emotional- associative memory, as well as molecular, enzymatic and histological assays to evaluate selected biochemical parameters. Our study showed that JM-20 prevented memory decline alongside with the inhibition of aluminum-induced alterations of oxidative parameters, and increase of AChE activity and of tumor necrosis factor alpha (TNF-α) levels. JM-20 also preserved anti-apoptotic proteins and protected against axonal and neuronal damaged in the hippocampus and prefrontal cortex. Altogether, our findings expanded our understanding of the ability of JM-20 to preserve essential types of memory in rats under neurotoxic conditions, and suggest its potential capacity to counteract etiological factors of AD by breaking the progression of key neurodegeneration-associated steps in a rat model of the disease.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

“…The absorbance was read at 412 nm during 20 min at 1 min interval. The AChE activity was expressed as μmol of (ATCh) iodide hydrolyzed per min per mg protein [16,32].…”

Section: Acetylcholinesterase Activity On Brain Homogenatementioning

confidence: 99%

Section: Mitochondrial Assaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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