Spatial Learning Responses to Lipopolysaccharide in Adult and Aged Rats

Kupferschmid, Barbara; Therrien, Barbara

doi:10.1177/1099800417726875

Cited by 9 publications

(15 citation statements)

References 42 publications

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“…In line with these findings, in our present study, LPS-challenged rats showed less bodyweight gain, less exploratory behavior, anhedonia, and despair behaviors. Using directional heading error as the evaluation index, Kupferschmid and his colleagues reported a selective, age-dependent spatial learning impairment in LPSadministered rats (Kupferschmid and Therrien, 2017). In the present study, although there was no significant difference among groups in the MWM tasks, the LPS-challenged rats showed a decline of novel arm preference index in the Y-maze.…”

Section: Discussioncontrasting

confidence: 55%

Quercetin Alleviates LPS-Induced Depression-Like Behavior in Rats via Regulating BDNF-Related Imbalance of Copine 6 and TREM1/2 in the Hippocampus and PFC

Chen

et al. 2020

Front. Pharmacol.

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Quercetin is a polyphenol with multiple biological activities, and results of our preliminary study showed that it could shorten the immobility time of mice in the forced swimming test and tail suspending test. The aim of this study was to investigate its effects on the behavioral performance of lipopolysaccharide (LPS)-challenged rats and explore the potential mechanism. The results showed that intragastrical administration of quercetin (40 mg/kg) could improve the bodyweight gain of LPS-challenged rats, increase the saccharin preference index in the saccharin preference test and the novel arm preference index in the Y-maze, and decrease the immobility time in the FST. However, it showed no significant effect on the performance of LPS-challenged rats in the Morris water maze and the plasma concentrations of nesfatin-1, C-reactive protein (CRP), and IL-6. Results of western blot showed that the expression levels of BDNF, Copine 6, p-TrkB, and the triggering receptors expressed on myeloid cells (TREM) 1 were decreased in both the hippocampus and the prefrontal cortex (PFC) of LPS-challenged rats, while the expression of TREM2 was increased. The protein expression of synapsin-1 was decreased in the hippocampus without significant changes in the PFC. These imbalance protein expressions could be balanced by treatment with quercetin. The results suggested that quercetin could alleviate LPS-induced depression-like behaviors and impairment of learning and memory in rats, the mechanism of which might be involved with regulating the BDNF-related imbalance expression of Copine 6 and TREM1/2 in the hippocampus and the PFC.

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Section: Discussioncontrasting

confidence: 55%

Quercetin Alleviates LPS-Induced Depression-Like Behavior in Rats via Regulating BDNF-Related Imbalance of Copine 6 and TREM1/2 in the Hippocampus and PFC

Chen

et al. 2020

Front. Pharmacol.

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“…The solution of LPS (from Escherichia coli 026:B6, Sigma-Aldrich, St. Louis, MO, USA) in 1 mL of saline at a concentration of 250 µg/kg was administrated intraperitoneally [ 38 , 39 ] to the male offspring from the control + LPS, MIA responsive + LPS and MIA non-responsive + LPS groups at PND120. The control + vehicle, MIA responsive + vehicle and MIA non-responsive + vehicle groups received an intraperitoneal injection of vehicle (saline) in the corresponding volume (1 mL/kg).…”

Section: Methodsmentioning

confidence: 99%

Maternal Immune Activation Sensitizes Male Offspring Rats to Lipopolysaccharide-Induced Microglial Deficits Involving the Dysfunction of CD200–CD200R and CX3CL1–CX3CR1 Systems

Chamera

Szuster-Głuszczak

Trojan

et al. 2020

Cells

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Early life challenges resulting from maternal immune activation (MIA) may exert persistent effects on the offspring, including the development of psychiatric disorders, such as schizophrenia. Recent evidence has suggested that the adverse effects of MIA may be mediated by neuron–microglia crosstalk, particularly CX3CL1–CX3CR1 and CD200–CD200R dyads. Therefore, the present study assessed the behavioural parameters resembling schizophrenia-like symptoms in the adult male offspring of Sprague-Dawley rats that were exposed to MIA and to an additional acute lipopolysaccharide (LPS) challenge in adulthood, according to the “two-hit” hypothesis of schizophrenia. Simultaneously, we aimed to clarify the role of the CX3CL1–CX3CR1 and CD200–CD200R axes and microglial reactivity in the brains of adult offspring subjected to MIA and the “second hit” wit LPS. In the present study, MIA generated a range of behavioural changes in the adult male offspring, including increased exploratory activity and anxiety-like behaviours. The most intriguing finding was observed in the prepulse inhibition (PPI) test, where the deficit in the sensorimotor gating was age-dependent and present only in part of the rats. We were able to distinguish the occurrence of two groups: responsive and non-responsive (without the deficit). Concurrently, based on the results of the biochemical studies, MIA disrupted mainly the CD200–CD200R system, while the changes of the CX3CL1–CX3CR1 axis were less evident in the frontal cortex of adult non-responsive offspring. MIA markedly affected the immune regulators of the CD200–CD200R pathway as we observed an increase in cortical IL-6 release in the responsive group and IL-4 in the non-responsive offspring. Importantly, the “second hit” generated disturbances at the behavioural and biochemical levels mostly in the non-responsive adult animals. Those offspring were characterized both by disturbed PPI and “priming” microglia. Altogether, the exposure to MIA altered the immunomodulatory mechanisms, including the CD200–CD200R axis, in the brain and sensitized animals to subsequent immunological challenges, leading to the manifestation of schizophrenia-like alterations.

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“…The procedure to reconstitute LPS was described previously. 15 Sample sizes were the following: CW—50 µg/kg LPS ( n = 1 per age group), 100 µg/kg LPS ( n = 1 per age group), or saline ( n = 2 per age group); WW—100 µg/kg LPS (adult: n = 2; aged: n = 4) or saline (adult: n = 2; aged: n = 4). Because only one animal in each age group received either 50 or 100 µg/kg LPS in CW, those animals were combined into one experimental group for the purpose of analysis.…”

Section: Methodsmentioning

confidence: 99%

“…SAS Proc Mixed (SAS Institute, Cary, NC) was used to analyze the data as described previously. 15 Models with homogeneous error variances among the groups were also considered with the best fit determined using Model fit statistics. Using the Mixed procedure, the fixed effects of experimental status (control vs experimental), age (adult vs aged), day (days 1 to 5; day 5 vs retention days), water (cold vs warm) and the interactions between experimental status, age, day, and water were examined, while allowing the variances of the random measurement errors to vary across the groups.…”

Section: Methodsmentioning

confidence: 99%

“… 10 , 11 Effects of an LPS challenge have also been shown to be dose-related with the highest doses resulting in the greatest weight loss. 12 , 13 However, cognitive problems, specifically spatial learning deficits, occur following administration of high-dose LPS 14 , 15 or low-dose LPS, 16 while aged animals also display long-term memory deficits following an immune challenge with Escherichia coli . 17 To date, few studies have evaluated the effects of low-dose LPS administration and age on spatial learning.…”

Section: Introductionmentioning

confidence: 99%

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Effects of low-dose lipopolysaccharide and age on spatial learning in different Morris water maze protocols

2017

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Objectives:Animals administered lipopolysaccharide exhibit dose-related sickness behaviors (decreased food intake, weight loss, and cognitive changes). While research has demonstrated that spatial learning is impaired following a lipopolysaccharide immune challenge, the results differ depending on the methodology used to evaluate spatial learning. Additionally, few studies have evaluated the effects of low-dose lipopolysaccharide on spatial learning. Therefore, we assessed spatial learning, food intake, and weight changes in adult and aged rats after a low-dose lipopolysaccharide immune challenge in the Morris water maze using two water temperatures.Methods:Adult (5–6 months) and aged (22 months) male Brown-Norway rats were administered either 50 or 100 μg/kg lipopolysaccharide or saline, and then tested in the Morris water maze for 5 days, rested for 7 days, and later underwent 2 days of retention tests. Probe trials were conducted at the end of initial and retention testing.Results:Low-dose lipopolysaccharide administration did not result in food intake or weight changes. While the aged experimental group took longest to improve directional heading error in both cold and warm water, heading error was greater in cold water. Behavioral testing revealed an apparent age and water temperature effect on swim time. Retention and probe trial results showed that aged experimental animals had the worst performance in cold water.Conclusion:We conclude that while low-dose lipopolysaccharide did not result in typical sickness behaviors (decreased food intake or weight), spatial learning and memory were impaired in the aged experimental group. These results have important implications for the care of elderly individuals experiencing mild to moderate infections.

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Spatial Learning Responses to Lipopolysaccharide in Adult and Aged Rats

Cited by 9 publications

References 42 publications

Quercetin Alleviates LPS-Induced Depression-Like Behavior in Rats via Regulating BDNF-Related Imbalance of Copine 6 and TREM1/2 in the Hippocampus and PFC

Quercetin Alleviates LPS-Induced Depression-Like Behavior in Rats via Regulating BDNF-Related Imbalance of Copine 6 and TREM1/2 in the Hippocampus and PFC

Maternal Immune Activation Sensitizes Male Offspring Rats to Lipopolysaccharide-Induced Microglial Deficits Involving the Dysfunction of CD200–CD200R and CX3CL1–CX3CR1 Systems

Effects of low-dose lipopolysaccharide and age on spatial learning in different Morris water maze protocols

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