Research Article
Lipopolysaccharide-Induced Spatial Memory and Synaptic
Plasticity Impairment Is Preventable by Captopril
Azam Abareshi,
1
Akbar Anaeigoudari,
2
Fatemeh Norouzi,
3
Mohammad Naser Shafei,
1
Mohammad Hossein Boskabady,
4
Majid Khazaei,
4
and Mahmoud Hosseini
1
1
Neurocognitive Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2
Department of Physiology, School of Medicine, Jirof University of Medical Sciences, Jirof, Iran
3
Department of Physiology, Esfarayen Faculty of Medical Sciences, Esfarayen, Iran
4
Neurogenic Infammation Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Correspondence should be addressed to Mahmoud Hosseini; hosseinim@mums.ac.ir
Received 25 April 2016; Revised 20 August 2016; Accepted 22 September 2016
Academic Editor: Jo˜ ao Quevedo
Copyright © 2016 Azam Abareshi et al. Tis is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Introduction. Renin-angiotensin system has a role in infammation and also is involved in many brain functions such as learning,
memory, and emotion. Neuroimmune factors have been proposed as the contributors to the pathogenesis of memory impairments.
In the present study, the efect of captopril on spatial memory and synaptic plasticity impairments induced by lipopolysaccharide
(LPS) was investigated. Methods. Te rats were divided and treated into control (saline), LPS (1mg/kg), LPS-captopril (LPS-
Capto; 50 mg/kg captopril before LPS), and captopril groups (50 mg/kg) before saline. Morris water maze was done. Long-term
potentiation (LTP) from CA1 area of hippocampus was assessed by 100 Hz stimulation in the ipsilateral Schafer collateral pathway.
Results. In the LPS group, the spent time and traveled path to reach the platform were longer than those in the control, while, in the
LPS-Capto group, they were shorter than those in the LPS group. Moreover, the slope and amplitude of feld excitatory postsynaptic
potential (fEPSP) decreased in the LPS group, as compared to the control group, whereas, in the LPS-Capto group, they increased
compared to the LPS group. Conclusion. Te results of the present study showed that captopril improved the LPS-induced memory
and LTP impairments induced by LPS in rats. Further investigations are required in order to better understand the exact responsible
mechanism(s).
1. Introduction
Renin-angiotensin system (RAS) is one of the neuropeptide
systems in the brain. Te substrate of RAS, angiotensinogen,
is cleaved by the renin enzyme to form the decapeptide
angiotensin (Ang I) in the brain [1]. Ang I is then converted
to an octapeptide, Ang II, by angiotensin converting enzyme
(ACE) [2] which is extensively located within various areas
of central nervous system (CNS) [3]. Ang II is cleaved by
glutamyl aminopeptidase A (AP-A) to form heptapeptide,
Ang III. Ang II can also be cleaved to Ang (1-7) by car-
boxypeptidase P [2]. In addition, ACE2 acts on Ang I and Ang
II to form Ang 1-9 and Ang 1-7, respectively. ACE2 has been
shown to have a higher efciency for conversion of Ang II to
Ang 1-7 than for conversion of Ang I to Ang 1-9. Tis enzyme
has been expressed in a low concentration in the CNS [4]. Te
main efector of RAS, Ang II, binds to specifc receptors in the
brain to induce multiple actions [5]. It also regulates blood
pressure, sodium and water balance, and sexual behaviors [2,
6]. Te brain RAS has been shown to be involved in memory
loss associated diseases such as Alzheimer’s disease (AD)
[1, 7] and cognitive dysfunctions which are preventable by
angiotensin converting enzymes (ACE) inhibitors including
captopril [1, 8]. Long-term potentiation (LTP), one of the
major forms of activity dependent synaptic plasticity, is the
primary experimental model for evaluating the synaptic basis
of learning and memory in the hippocampus of vertebrates
[9, 10]. An enhanced level of Ang II has been reported to be
able to inhibit LTP induction in hippocampus [8].
In addition, RAS has been proposed to have a role
in infammatory responses and lipopolysaccharide- (LPS-)
mediated microglial activation [11]. On the other hand, ACE
Hindawi Publishing Corporation
Advances in Medicine
Volume 2016, Article ID 7676512, 8 pages
http://dx.doi.org/10.1155/2016/7676512