Epicatechin Reduces Spatial Memory Deficit Caused by Amyloid-β25⁻35 Toxicity Modifying the Heat Shock Proteins in the CA1 Region in the Hippocampus of Rats.

Alfonso Diaz,Blanca Espinosa,Samuel Treviño,Sergio Montes,Nallely Cervantes,Francisca Pérez-Severiano,Moises Rubio-Osornio,Karla Rojas,Jorge Guevara,Estefanía Martínez-Muñoz,Guadalupe Pulido-Fernandez

doi:10.3390/antiox8050113

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by dementia and the aggregation of the amyloid beta peptide (Aβ). Aβ25–35 is the most neurotoxic sequence, whose mechanism is associated with the neuronal death in the Cornu Ammonis 1 (CA1) region of the hippocampus (Hp) and cognitive damage. Likewise, there are mechanisms of neuronal survival regulated by heat shock proteins (HSPs). Studies indicate that pharmacological treatment with flavonoids reduces the prevalence of AD, particularly epicatechin (EC), which shows better antioxidant activity. The aim of this work was to evaluate the effect of EC on neurotoxicity that causes Aβ25–35 at the level of spatial memory as well as the relationship with immunoreactivity of HSPs in the CA1 region of the Hp of rats. Our results show that EC treatment reduces the deterioration of spatial memory induced by the Aβ25–35, in addition to reducing oxidative stress and inflammation in the Hp of the animals treated with EC + Aβ25–35. Likewise, the immunoreactivity to HSP-60, -70, and -90 is lower in the EC + Aβ25–35 group compared to the Aβ25–35 group, which coincides with a decrease of dead neurons in the CA1 region of the Hp. Our results suggest that EC reduces the neurotoxicity induced by Aβ25–35, as well as the HSP-60, -70, and -90 immunoreactivity and neuronal death in the CA1 region of the Hp of rats injected with Aβ25–35, which favors an improvement in the function of spatial memory.

Highlights

Alzheimer’s disease (AD) is a neurodegenerative disorder that affects the senile population and is characterized clinically by loss of memory and difficulty in reasoning
The comparative analysis indicates that the group administered with Aβ25–35 showed a significantly longer latency time compared to the control group and the group administered only with EC on the different days that the training test was performed (one-way Analysis of Variance (ANOVA), p < 0.05)
The group administered with EC + Aβ25–35 showed a latency time to find the platform lower in comparison with the group administered only with Aβ25–35 with a statistically significant difference that was observed from day 2 of training until the end of the test (One-way ANOVA, p < 0.05) (Figure 1A)

Summary

Introduction

Alzheimer’s disease (AD) is a neurodegenerative disorder that affects the senile population and is characterized clinically by loss of memory and difficulty in reasoning. Neurofibrillary tangles (MNF) are formed by the hyperphosphorylated tau protein. Neuritic plaques (PNs) are formed by the amyloid-β peptide, which coexists with reactive astrogliosis and neuronal death in brain regions such as the cerebral cortex and the hippocampus (Hp) [1]. The amyloid-β (Aβ), the main component of the PNs, comes from the alternative hydrolysis of the amyloid precursor protein (PPA) [2]. There are several functional domains, characterized by a neurotoxic domain (25–35), of the amino acid sequence of Aβ that stand out. Several research groups propose the use of this neurotoxic domain as an experimental model to study AD [3,4]

Objectives

Methods

Results

Discussion

Conclusion