Alzheimer's disease (AD) is a pathology of multifactorial etiology that affects million people per years [1]. AD was first described of Alois Alzheimer in 1906 and is characterized by accumulation of amyloid plaques, tau protein-mediated neurodegeneration and cognitive impairment [2]. The susceptibility to AD is the result of multiple environmental and genetic determinants during life [3]. In this sense, the epigenetic changes have been increasingly studied due to the physiological alterations they cause during of life cycle, being inferred in the pathophysiology of neurodegenerative diseases as AD [4,5].

In view of above mentioned, the main epigenetic alterations are DNA methylation, histone modification, chromatin modification and regulation of non-coding RNA [6]. It is known that, histone modification is usually post-transcriptional and occurs by different mechanisms, for example, acetylation, methylation, phosphorylation and ubiquitination [7].

In this context, histone acetylation is a reversible reaction which requires a dynamic balance between two enzymes: histone acetyltransferases (HAT) and histone deacetylases (HDAC) [8]. In DA, the histone acetylation in temporal cortex is decreased, while HDAC activity is low, which leads to a reduction in the expression of regulatory genes involved in postsynaptic activity [9].

In view of scientific facts, Beta-Amyloid peptide (1−42) (Aβ1-42), is a major component of amyloid deposits in central nervous system (SNC), involved in pathology of AD, Aβ1-42 is utilized in rodents to induce a model that AD-mimics. In addition, histone modification is associated with the hydrolysis of amyloid precursor protein (APP) and transcription of histone acetylation regulatory genes, in Aβ1-42 model [10]. Besides that, has already been elucidated that the use of HDAC inhibitor such as suberoylanilide hydroxamic acid (SAHA) can be attenuate epigenetic factors involved in some neurodegenerative diseases [8].

In view of aforementioned, cyclic adenosine monophosphate (cAMP), is involved in a signaling pathway which showed to play a crucial role in long-term memory formation [4]. In this pathway, CAMP-dependent protein kinase A (PKA), when activated allosterically by cAMP, can phosphorylate the cAMP response element binding protein (t-CREB) on serine 133 (p-CREB) [11]. Thus, it is known that pCREB increases short-term memory through the regulation of brain-derived neurotrophic factor (BDNF), suggesting that pCREB signaling is involved in short-and long-term memory formation [12].

Still, it's has been documented that pCREB-mediated BDNF expression. The BDNF gene expression are drastically decreased in hippocampus and some cortical areas of AD patient and in Aβ1-42-treated mice [13,14]. Several scientific showed that chromatin remodeling via histone acetylation regulates BDNF transcription [15,16]. In this context, HDAC inhibitors can be increased BDNF levels during in vivo memory formation [8,15,16].

Wherefore, the aim of current study was to characterize the mechanisms by which Aβ1-42 injection via intracerebroventricular (i.c.v.) induces neurobehavioral changes (involvement of HDAC and cAMP/PKA/pCREB pathway) in a time-course curve. Also, SAHA inhibitor of HDAC was used to investigate the involvement of epigenetic modifications Aβ1-42-caused.