IMR Press / JIN / Volume 21 / Issue 2 / DOI: 10.31083/j.jin2102049
Open Access Original Research
Investigation of the optimal dose for experimental lipopolysaccharide-induced recognition memory impairment: behavioral and histological studies
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1 Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, 21589 Jeddah, Saudi Arabia
2 Department of Physiology, Neuroscience Unit, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
3 Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
*Correspondence: nsalahalzahrani@stu.kau.edu.sa (Noor Ahmed Alzahrani)
Academic Editors: Rafael Franco and Santosh Jadhav
J. Integr. Neurosci. 2022, 21(2), 49; https://doi.org/10.31083/j.jin2102049
Submitted: 29 October 2021 | Revised: 9 December 2021 | Accepted: 24 December 2021 | Published: 21 March 2022
(This article belongs to the Special Issue Neuro-immune modulations in Alzheimer's disease)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Lipopolysaccharide (LPS) administration is one of the most commonly used methods for inducing inflammation in animal models. Several animal studies have investigated the effects of acute and chronic peripheral administration of LPS on cognitive impairment. However, no previous study has compared the effects of different doses of chronically administered LPS on recognition memory performance. Aim: Here, we aimed to investigate the optimal dose of chronically administered LPS for the induction of recognition memory impairment in mice. Materials and methods: LPS at different doses (0.25, 0.50 and 0.75 mg/kg) was administered to SWR/J mice daily for 7 days. On day 9, the open field, novel object recognition and novel arm discrimination behavioral tests were performed. Additionally, prefrontal cortical histological examination was conducted. Results: Compared with the control group, mice injected with 0.75 mg/kg LPS notably showed no object preference (familiar vs. novel), a reduction in the discrimination index, and spatial recognition impairment. Administration of the 0.25 and 0.50 mg/kg doses of LPS showed a preference for the novel object compared with the familiar object, had no significant impact on the discrimination index, and caused spatial recognition impairment. These behavioral results are in line with the histological examination of the prefrontal cortex, which revealed that the 0.75 mg/kg dose produced the most histological damage. Conclusions: Our findings suggest that for chronic peripheral administration of LPS, 0.75 mg/kg is the optimal dose for inducing neuroinflammation-associated recognition memory deficits.

Keywords
Lipopolysaccharide
Neuroinflammation
Recognition memory
Prefrontal cortex
Chronic
Alzheimer disease
Peripheral administration
Recognition memory loss
Novel arm discrimination task
Acute
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