Lipopolysaccharide impairs long-term potentiation and recognition memory and increases p75NTR expression in the rat dentate gyrus

Hennigan, Amy; Trotter, Claire E.; Kelly, Aine Marie

doi:10.1016/j.brainres.2006.10.066

Cited by 62 publications

(35 citation statements)

References 38 publications

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“…This treatment caused increased numbers of microglia with phagocytotic activity (Iba1 ϩ /ED1 ϩ ) in the SGZ/ GCL, both at the time when the new cells were born (1 week after LPS injection) and when they had reached the mature state (at the time of recording and morphological analysis, 7 weeks later). Consistent with our findings, Herber et al (2006) potentiation (Vereker et al, 2000;Hennigan et al, 2007). Furthermore, injection of LPS in the hippocampal CA1 area of rats gives rise to learning and memory deficits and decreased glutamatergic neurotransmission but no cell death (Tanaka et al, 2006).…”

Section: Discussionsupporting

confidence: 90%

Inflammation Regulates Functional Integration of Neurons Born in Adult Brain

Jakubs¹,

Bonde²,

Iosif³

et al. 2008

J. Neurosci.

132

117

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Inflammation influences several steps of adult neurogenesis, but whether it regulates the functional integration of the new neurons is unknown. Here, we explored, using confocal microscopy and whole-cell patch-clamp recordings, whether a chronic inflammatory environment affects the morphological and electrophysiological properties of new dentate gyrus granule cells, labeled with a retroviral vector encoding green fluorescent protein. Rats were exposed to intrahippocampal injection of lipopolysaccharide, which gave rise to longlasting microglia activation. Inflammation caused no changes in intrinsic membrane properties, location, dendritic arborization, or spine density and morphology of the new cells. Excitatory synaptic drive increased to the same extent in new and mature cells in the inflammatory environment, suggesting increased network activity in hippocampal neural circuitries of lipopolysaccharide-treated animals. In contrast, inhibitory synaptic drive was more enhanced by inflammation in the new cells. Also, larger clusters of the postsynaptic GABA A receptor scaffolding protein gephyrin were found on dendrites of new cells born in the inflammatory environment. We demonstrate for the first time that inflammation influences the functional integration of adult-born hippocampal neurons. Our data indicate a high degree of synaptic plasticity of the new neurons in the inflammatory environment, which enables them to respond to the increase in excitatory input with a compensatory upregulation of activity and efficacy at their afferent inhibitory synapses.

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Section: Discussionsupporting

confidence: 90%

Inflammation Regulates Functional Integration of Neurons Born in Adult Brain

Jakubs¹,

Bonde²,

Iosif³

et al. 2008

J. Neurosci.

132

117

View full text Add to dashboard Cite

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“…Therefore, it is possible that p38 MAPK achieves these roles, in part, by increasing expression of p75 NTR . Consistent with this hypothesis is the observation that LPS, which leads to the stabilization of several transcripts through the p38 MAPK/MK2 pathway, also induces p75 NTR expression (23,46,47). One mechanism by which the p38 MAPK pathway has been shown to stabilize target transcripts involves the RNA binding protein HuR (22,(29)(30)(31).…”

Section: Because Induction Of P75mentioning

confidence: 73%

The p38 MAPK Pathway Mediates Aryl Propionic Acid–Induced Messenger RNA Stability of p75NTR in Prostate Cancer Cells

Quann¹,

Khwaja²,

Djakiew

2007

Cancer Research

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The p75 NTR acts as a tumor suppressor in the prostate, but its expression is lost as prostate cancer progresses and is minimal in established prostate cancer cell lines such as PC-3, DU-145, and LNCaP. Previously, we showed that treatment with R-flurbiprofen or ibuprofen induced p75 NTR expression in PC-3 and DU-145 cells leading to p75 NTR -mediated decreased survival. Here, we investigate the mechanism by which these drugs induce p75 NTR expression. We show that the observed increase in p75NTR protein due to R-flurbiprofen and ibuprofen treatment was accompanied by an increase in p75 NTR mRNA, and this increase in mRNA was the result of increased mRNA stability and not by an up-regulation of transcription. In addition, we show that treatment with R-flurbiprofen or ibuprofen led to sustained activation of the p38 mitogen-activated protein kinase (MAPK) pathway. Furthermore, inhibition of the p38 MAPK pathway with the p38 MAPK-specific inhibitor SB202190 or by small interfering RNA (siRNA) knockdown of p38 MAPK protein prevented induction of p75 NTR by R-flurbiprofen and ibuprofen. We also observed that siRNA knockdown of MAPK-activated protein kinase (MK)-2 and MK3, the kinases downstream of p38 MAPK that are responsible for the mRNA stabilizing effects of the p38 MAPK pathway, also prevented an induction of p75 NTR by R-flurbiprofen and ibuprofen. Finally, we identify the RNA stabilizing protein HuR and the posttranscriptional regulator eukaryotic translation initiation factor 4E as two possible mechanisms by which the p38 MAPK pathway may increase p75 NTR expression. Collectively, the data suggest that R-flurbiprofen and ibuprofen induce p75 NTR expression by increased mRNA stability that is mediated through the p38 MAPK pathway. [Cancer Res 2007;67(23):11402-10]

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“…Chronic inflammation with microglial activation has been implicated as a causative factor in several neurodegenerative diseases, including Alzheimer's, 24 and has been associated with cognitive decline in both humans and animals. 25 Activated microglia elaborate interleukin-1␤ and other cytokines that appear to precipitate cognitive impairment 26,27 by interference with synaptic plasticity. In addition, blocking microglial activation has been shown to preserve spatial memory.…”

Section: Discussionmentioning

confidence: 99%

Microemboli Composed of Cholesterol Crystals Disrupt the Blood-Brain Barrier and Reduce Cognition

Rapp

Pan

Neumann

et al. 2008

Stroke

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Background and Purpose-Microemboli occur frequently in patients with asymptomatic carotid atherosclerosis. In other vascular beds, microemboli are known to initiate an inflammatory response, causing organ dysfunction. In the current study, we investigated whether emboli composed of cholesterol crystals, a component of human atherosclerotic plaque, could also cause inflammation and brain dysfunction demonstrated by cognitive impairment. Methods-Cholesterol crystals of 60 to 100 m were injected via the rat internal carotid artery. T2-weighted magnetic resonance imaging was conducted after 3 days to estimate infarct volume. Brains were examined for matrix metalloproteinase activation at 24 hours and for albumin leakage and microglia and astrocyte activation at 4 days and 1, 2, and 4 weeks after embolization. To determine changes in cognition, behavioral tests including open field, motor learning, and Barnes Maze tests were conducted on young adult and middle-aged rats 4 weeks after either a single injection or after repeated, bilateral injections given at an interval of 2 weeks. Results-Matrix metalloproteinase activation was detected in 50% of the animals examined. Perivascular albumin staining was found at 4 days but rarely persisted beyond 1 week. Activation of microglia and astrocytes occurred in all animals and persisted for up to 8 weeks. Cognitive impairment was observed in middle-aged rats after repeated, bilateral injections but not after single injections. In these animals, areas of inflammation were small and scattered but often involved the striatum and hippocampus. Conclusions-Cholesterol embolization caused an inflammatory response in the brain with persistent activation of microglia and astrocytes and led to cognitive impairment after repeated injections in middle-aged animals with only small foci of neural injury. These data indicate that microembolization causes inflammation and that minimal neuronal injury can cause cognitive impairment in older animals.

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Lipopolysaccharide impairs long-term potentiation and recognition memory and increases p75NTR expression in the rat dentate gyrus

Cited by 62 publications

References 38 publications

Inflammation Regulates Functional Integration of Neurons Born in Adult Brain

Inflammation Regulates Functional Integration of Neurons Born in Adult Brain

The p38 MAPK Pathway Mediates Aryl Propionic Acid–Induced Messenger RNA Stability of p75NTR in Prostate Cancer Cells

Microemboli Composed of Cholesterol Crystals Disrupt the Blood-Brain Barrier and Reduce Cognition

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