**1. 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. At the histopathological level, 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].

The intrahippocampal injection of Aβ25–35 promotes the neurodegeneration accompanied by a deterioration in spatial memory [5,6]. Our previous results show that the undecapeptide generates an inflammatory response. This is evidenced by reactive astrogliosis and the release of proinflammatory cytokines such as interleukin-1 beta (IL-1β) and Tumor necrosis factor-alpha (TNF-α) [7], besides exacerbation of the production of reactive oxygen species (ROS) and lipid peroxidation, implying the generation of a chronic state of oxidative stress and cell death [4]. At the cellular level, the expression of heat shock proteins (HSPs), chaperones that participate in the assembly, transport, and degradation of proteins under both normal and stress conditions, has been demonstrated to be a cell survival mechanism [8]. Several reports indicate that the Aβ increases the expression of HSP-60, HSP-70, and HSP-90 as a protection mechanism against the toxicity of this peptide [9,10]. HSPs participate in cellular proteostasis and a reduction in the death of hippocampal neurons [11]. However, these reports indicate that the increase in these HSPs is not enough to reverse the neurotoxicity caused by the injection of Aβ into the rat Hp. Consequently, this causes neuronal and cognitive impairment [9].

In this sense, it is necessary to evaluate new molecules that, together with the HSP activity, can help to prevent or inhibit oxidative stress, the inflammatory response, and thus dementia. This could reverse the neurodegeneration induced by Aβ25–35 and be considered as a therapeutic alternative for AD. Recent reports indicate that epicatechin (EC), a flavonoid present in fruit and vegetables, has aroused grea<sup>t</sup> interest because of its beneficial antioxidant properties, also being used in the treatment and prevention of cancer as well as delaying aging [12,13]. The main biological activity of EC is the formation of protein complexes, the inhibition of free radicals, and the reduction of lipid peroxidation, making it an excellent antioxidant [14]. In addition, it can act as an anti-inflammatory by inhibiting cyclo-oxygenases and improving endothelial function [15,16].

Previously, it has been observed that EC treatment promotes the neuronal plasticity in the Hp and cortex, moreover improving spatial memory processes [16]. Also, EC prevents the toxicity induced by Aβ25–35 by reducing ROS and LP levels and reactive astrogliosis, and by not causing a deterioration of spatial memory [17,18]. However, it is not known how the anti-inflammatory and antioxidative activity of EC modifies the immunoreactivity of HSP-60, HSP-70, and HSP-90 in response to Aβ25–35 toxicity. The objective of this work is to evaluate the effect of EC administration on spatial memory, the oxidative-inflammatory response, and its relationship with HSPs after an intrahippocampal injection of Aβ25–35.

#### **2. Materials and Methods**
