Lipopolysaccharide inhibits induction of long-term potentiation and depression in the rat hippocampal CA1 area

Jo, Jihoon; Park, Eun Jin; Lee, Jae-Kwang; Jung, MinWhan; Lee, Chang‐Joong

doi:10.1016/s0014-2999(01)01075-5

Cited by 27 publications

(16 citation statements)

References 24 publications

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“…This assumption is further supported by the observation that inhibition of NOS2 by aminoguanidine attenuated learning and memory deficits in a four-vessel occlusion model of cerebral ischemia ). In line with this, it has been shown that hippocampal LTP, a major indicator of synaptic efficacy underlying learning and memory formation (Malenka and Nicoll, 1999;Malenka and Bear, 2004), was reduced by LPS in vitro and in vivo (Cunningham et al, 1996;Commins et al, 2001;Jo et al, 2001). Importantly, inhibition of NOS2 has been found to prevent inflammatory suppression of LTP in similar models Togashi et al, 2001;Wang et al, 2004).…”

Section: Discussionmentioning

confidence: 78%

“…In line with these findings, LPS has been demonstrated to impair long-term potentiation (LTP), a key cellular process of learning and memory consolidation (Malenka and Nicoll, 1999), in vitro and in vivo Jo et al, 2001;Hennigan et al, 2007). However, these investigations are likely to reflect the immediate effects of SE on brain functions, since the experimental paradigms applied were of rather acute nature, exposing animals or brain slices to LPS directly or just hours before the respective analysis.…”

Section: Introductionmentioning

confidence: 95%

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NOS2Gene Deficiency Protects from Sepsis-Induced Long-Term Cognitive Deficits

Weberpals¹,

Hermes²,

Hermann³

et al. 2009

J. Neurosci.

132

105

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To date, long-term consequences of septic encephalopathy on cerebral metabolism, cognition, learning, and memory capabilities and factors involved are poorly understood. In this study, we used a murine sepsis model to demonstrate that bacterial lipopolysaccharide (LPS) causes long-term cognitive deficits in mice. Two months after LPS treatment, wild-type mice committed more working and reference memory errors than controls. The behavioral impairment was independent of the cerebral glucose uptake as evidenced by 18 F-Fluordeoxyglucose small animal positron emission tomography. In contrast, mice deficient for the inducible nitric oxide synthase gene (NOS2Ϫ/Ϫ) did not show any cognitive changes when challenged with LPS. Immunohistochemical analysis demonstrated that LPS did not lead to neuronal cell death but caused sustained microglial activation in wild-type as compared to NOS2Ϫ/Ϫ mice. Expression analysis showed that LPS-treated NOS2Ϫ/Ϫ mice had lower brain mRNA levels for proinflammatory factors compared with wild-type mice. Expression analysis demonstrated distinct changes in the content of synaptic proteins in wild-type mice, which were not observed in the NOS2Ϫ/Ϫ mice. Together, this data set outlines the importance of the NOS2 activation for long-term cerebral changes after severe sepsis.

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Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 95%

NOS2Gene Deficiency Protects from Sepsis-Induced Long-Term Cognitive Deficits

Weberpals¹,

Hermes²,

Hermann³

et al. 2009

J. Neurosci.

132

105

View full text Add to dashboard Cite

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“…The effects of acute or chronic exposure of LPS on GABAmediated synaptic inhibition have never been previously investigated. Earlier studies have shown that acute LPS exposure ( 60 min) does not affect extracellularly recorded field EPSPs (fEPSPs) (Cunningham et al, 1996;Jo et al, 2001;Mizuno et al, 2004) but blocked paired-pulse facilitation (PPF) of fEPSPs in the hippocampus in vivo (Commins et al, 2001) and acutely impaired long-term potentiation (LTP) (Cunningham et al, 1996;Mizuno et al, 2004). Although the mechanisms underlying these effects were not elucidated, an enhancement in GABAergic inhibition similar to what we observed could underlie these effects, as it is well established that increases in GABAergic inhibition can reduce PPF and hinder LTP induction (Davies et al, 1990;Kuenzi et al, 2000;Meredith et al, 2003;Kleschevnikov et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Chronic LPS exposure produces changes in intrinsic membrane properties and a sustained IL-β-dependent increase in GABAergic inhibition in hippocampal CA1 pyramidal neurons

et al. 2005

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Chronic inflammation has been reported to be a significant factor in the induction and progression of a number of chronic neurological disorders including Alzheimer's disease and Down syndrome. It is believed that inflammation may promote synaptic dysfunction, an effect that is mediated in part by pro-inflammatory cytokines such as interleukin-1beta (IL-1beta). However, the role of IL-1beta and other cytokines in synaptic transmission is still poorly understood. In this study, we have investigated how synaptic transmission and neuronal excitability in hippocampal pyramidal neurons are affected by chronic inflammation induced by exposing organotypic slices to the bacterial cell-wall product lipopolysaccharide (LPS). We report that CA1 pyramidal neurons recorded in whole cell from slices previously exposed to LPS for 7 days had resting membrane potential and action potential properties similar to those of the controls. However, they had significantly lower membrane resistance and a more elevated action potential threshold, and displayed a slower frequency of action potential discharge. Moreover, the amplitude of pharmacologically isolated postsynaptic gamma-aminobutyric acid (GABA)ergic potentials, but not excitatory glutamatergic postsynaptic potentials, was significantly larger following chronic LPS exposure. Interestingly, co-incubation of the IL-1 receptor antagonist (IL-1Ra) concurrently with LPS prevented the increase in GABAergic transmission, but not the reduction in intrinsic neuronal excitability. Finally, we confirmed that LPS dramatically increased IL-1beta, and IL-1beta-dependent IL-6 levels in the culture medium for 2 days before returning to baseline. We conclude that CA1 pyramidal neurons in slices chronically exposed to LPS show a persistent decrease in excitability due to a combined decrease in intrinsic membrane excitability and an enhancement in synaptic GABAergic input, the latter being dependent on IL-1beta. Therefore, chronic inflammation in hippocampus produces IL-1beta-dependent and -independent effects in neuronal and synaptic function that could contribute significantly to cognitive disturbances.

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“…These inflammation-associated elements activate microglia and astroglia present inside and outside of amyloid deposits, lead-Patil/Singh/Satyanarayan/Jain/Singh/ Kulkarni ing to intraneuronal damage [1]. Lipopolysaccharide (LPS), an endotoxin, is reported to induce various cytokines such as interleukin (IL) 1ß, IL-6, interferon alpha, tumor necrosis factor alpha [4], and cyclooxygenase-2 (COX-2) [5]. These proinflammatory mediators (IL-1ß, tumor necrosis factor alpha, and amyloid precursor protein mRNA), in turn, activate astrocytes and microglia in hippocampus, pituitary gland, and hypothalamus and produce degeneration of CA3 pyramidal neurons, leading to impairment in spatial memory.…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Flavonoids against Aging- and Lipopolysaccharide-Induced Cognitive Impairment in Mice

et al. 2003

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Flavonoids, naturally occurring polyphenolic compounds, are known to inhibit both lipopolysaccharide (LPS) stimulated tumor necrosis factor alpha and interleukin 6 release which modulate the proinflammatory molecules that have been reported in many progressive neurodegenerative disorders, including Alzheimer’s disease (AD), viral and bacterial meningitis, AIDS dementia complex, and stroke. The present experiments were performed to study the possible effects of exogenously administered flavonoids (apigenin-7-glucoside and quercetin) on the cognitive performance in aged and LPS-treated mice (an animal model for AD) using passive avoidance and elevated plus-maze tasks. Aged and LPS-treated mice showed poor retention of memory in step-through passive avoidance and in plus-maze tasks. Chronic administration of the flavonoids apigenin-7-glucoside (5–20 mg/kg i.p.) and quercetin (25–100 mg/kg i.p.) dose dependently reversed the age-induced and LPS-induced retention deficits in both test paradigms. However, flavonoids after chronic administration in young mice did not show any improvement of memory retention in both paradigms. Apigenin-7-glucoside showed more efficacy as compared with quercetin in both models that may be probably due to its greater efficacy to inhibit cyclooxygenase-2 and inducible nitric oxide synthase. Chronic treatment with flavonoids did not alter the locomotor activity in both young and aged mice; however, aged mice showed improvement of performance on Rota-Rod test. The results showed that chronic treatment with flavonoids reverses cognitive deficits in aged and LPS-intoxicated mice which suggests that modulation of cyclooxygenase-2 and inducible nitric synthase by flavonoids may be important in the prevention of memory deficits, one of the symptoms related to AD.

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Lipopolysaccharide inhibits induction of long-term potentiation and depression in the rat hippocampal CA1 area

Cited by 27 publications

References 24 publications

NOS2Gene Deficiency Protects from Sepsis-Induced Long-Term Cognitive Deficits

NOS2Gene Deficiency Protects from Sepsis-Induced Long-Term Cognitive Deficits

Chronic LPS exposure produces changes in intrinsic membrane properties and a sustained IL-β-dependent increase in GABAergic inhibition in hippocampal CA1 pyramidal neurons

Protective Effect of Flavonoids against Aging- and Lipopolysaccharide-Induced Cognitive Impairment in Mice

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