Lipopolysaccharide-Induced Spatial Memory and Synaptic Plasticity Impairment Is Preventable by Captopril

Abstract

Introduction. Renin-angiotensin system has a role in inflammation 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 effect of captopril on spatial memory and synaptic plasticity impairments induced by lipopolysaccharide (LPS) was investigated. Methods. The rats were divided and treated into control (saline), LPS (1 mg/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 Schaffer 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 field 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. The 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).

Figure 1

The protocol for the experiments.

Figure 2

Comparison of time latency to reach the platform in the Morris water maze test between the four groups. Data are presented as mean ± SEM (n = 10 in each group). ^∗ P < 0.05 and ^∗∗∗ P < 0.001 compared with the control group and ⁺⁺ P < 0.01 and ⁺⁺⁺ P < 0.001 compared with the LPS group.

Figure 3

Comparison of the distance traveled to reach the platform in the Morris water maze test between the four groups. Data are presented as mean ± SEM (n = 10 in each group). ^∗∗ P < 0.01 and ^∗∗∗ P < 0.001 compared with the control group and ⁺⁺ P < 0.01 and ⁺⁺⁺ P < 0.001 compared with the LPS group.

Figure 4

The results of the time spent in the target quadrant (Q1) in probe day, 24 hours after the last learning session. The platform was removed and the time spent in the target quadrant was compared between the groups. Data are shown as mean ± SEM (n = 10 in each group). ^∗∗ P < 0.01 compared with the control group and ⁺ P < 0.01 compared with the LPS group.

Figure 5

The results of the distance traveled in the target quadrant (Q1) in probe day, 24 hours after the last learning session. The platform was removed and the distance traveled in the target quadrant was compared between the groups. Data are shown as mean ± SEM (n = 10 in each group). ^∗∗∗ P < 0.001 compared with the control group and ⁺⁺ P < 0.01 compared with the LPS group.

Figure 6

The results of LTP induction in CA1 area of the hippocampus using 100 Hz tetanic stimulation at (a) the fEPSP amplitude and (b) the fEPSP slope. Data are presented as the average percentage changes from baseline responses. Each point shows mean ± SEM (n = 8 in each group). The amplitude and slope of fEPSP in the LPS group were lower than those in the control group (^∗∗ P < 0.01 and ^∗∗∗ P < 0.001) and in the LPS-Capto group they were higher with respect to the LPS group (⁺ P < 0.05 and ⁺⁺ P < 0.01).