Contents lists available at ScienceDirect Neuropeptides journal homepage: www.elsevier.com/locate/npep Neurogenesis and morphological-neural alterations closely related to amyloid β-peptide (25–35)-induced memory impairment in male rats Eleazar Ramírez a , Liliana Mendieta a , Gonzalo Flores b , I. Daniel Limón a, ⁎ a Laboratorio de Neurofarmacología edificio 105 C – FCQ, BUAP, Puebla, Mexico b Laboratorio de Neuropsiquiatría IF, BUAP, Puebla, Mexico ABSTRACT Memory impairment by the Amyloid-β 25–35 (Aβ 25–35 ) peptide in animal models has provided an understanding of the causes behind the similar deterioration that occurs in Alzheimer's disease. However, it is uncertain if a decrease of dendritic spines and neurogenesis conduces to cognitive impairment by an impairment in the re- trieval of stored memory. The aim of this study was to evaluate the consequences of impairment on spatial memory caused by the administration of the Aβ 25–35 peptide in the hippocampus, which is associated whit morphological changes and neurogenesis in the dentate gyrus (DG). The vehicle or Aβ 25–35 peptide (0.1 μg/μL) were bilaterally administered in the CA1 subfield of the rat hippocampus. The animals were tested for spatial learning and memory in the Morris Water Maze. In the day's 11, 18 and 32 after administration of the Aβ 25–35 peptide were examined the morphological changes in the DG using a Golgi-Cox stain. In the day 32, the neu- rogenesis was evaluated by the immunoreactivity to 5-bromo-2′-deoxyuridine (BrdU; 100 mg/kg, i.p.) that corresponding to cellular proliferation post damage, the neuronal specific nuclear protein (NeuN) and dou- blecortin (DCX). This study found a memory retrieval impairment occurring at day 17, a cognitive deficit which had increased significantly at day 31 after the administration of Aβ 25–35 peptide. These results are related to morphological changes in the granular cells of the DG, such as a shorter dendritic length and a decrease in the number of dendritic spines. In neurogenesis, the total number of cells positive to BrdU, NeuN and DCX in the hippocampal granule cell layer was found to have declined in animals treated with Aβ 25–35 . The results suggest that the Aβ 25–35 peptide impairs memory retrieval by decreasing the number of dendritic spines and altering neurogenesis in the DG. 1. Introduction Alzheimer's disease (AD) is a neurodegenerative disorder char- acterized by damage to the brain regions associated with learning and memory, such as the hippocampus (Haass and Selkoe, 2007; Karran et al., 2011). The aggregation of Amyloid-β (Aβ) is an early and critical event in the pathogenesis of AD, in which the abnormal production as well as the auto-aggregation of Aβ may trigger neuronal death and cognitive impairment (Roy et al., 2016). Aβ is a peptide comprising 40 to 42 amino acids, which can, in AD patients, produce shorter se- quences via the enzymatic cleavage of the N-terminal of amyloid-β 1–40/42, such as that which occurs with the production of amyloid-β 25–35 (Aβ 25–35 )(Kubo et al., 2002; Haass and Selkoe, 2007). The use of Aβ 25–35 peptide in animal models has contributed to the understanding of its effects on Aβ toxicity related mechanisms and its detrimental effect on spatial memory (Götz et al., 2011; Limón et al., 2011). Recent evidence suggests that the Aβ 25–35 peptide is able to both induce al- terations in neuronal activity and damage long-term memory by al- tering the dendritic spines (Lazcano et al., 2014). Several studies have previously demonstrated that, administration of the Aβ 25–35 peptide into the temporal cortex (TCx) or hippocampus (Hp) of rats induces cognitive deficit, caused by the ineffective encoding of new information (Limón et al., 2009; Díaz et al., 2011; Limón et al., 2011; Díaz et al., 2012). However, it remains uncertain whether the impairment cogni- tive is due to disrupted encoding and consolidation of information, or an impairment in the retrieval of stored memory information. The hippocampal formation is important for the acquisition of new memories, which occurs via a circuit composed of the entorhinal cortex (EC), the dentate gyrus (DG), and the CA3 and CA1 of the hippocampus. The information is processed and transmitted from the EC to the DG, from the DG to the CA3 pyramidal cells, and from the CA3 to the CA1 pyramidal cells, to be finally stored in the cortex (Amaral and Witter, https://doi.org/10.1016/j.npep.2017.11.001 Received 12 February 2017; Received in revised form 26 September 2017; Accepted 2 November 2017 ⁎ Corresponding author at: Laboratorio de Neurofarmacología, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 14 Sur & San Claudio, CU. San Manuel, 72570 Puebla, Mexico. E-mail address: daniel.limon@correo.buap.mx (I.D. Limón). Neuropeptides xxx (xxxx) xxx–xxx 0143-4179/ © 2017 Elsevier Ltd. All rights reserved. Please cite this article as: Ramírez, E., Neuropeptides (2017), http://dx.doi.org/10.1016/j.npep.2017.11.001