Osmotin attenuates LPS-induced neuroinflammation and memory impairments via the TLR4/NFκB signaling pathway

Badshah, Haroon; Ali, Tahir; Kim, Myeong Ok

doi:10.1038/srep24493

Cited by 196 publications

(167 citation statements)

References 52 publications

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“…In addition, there is a good correlation between the structure and function of the pyramidal cells in hippocampus and cortex and learning and memory functions . Histological observations of mouse brains showed damage to the pyramidal cells in hippocampus and cortex after LPS injections, characterized by extensive loss of Nissl substance and normal neuronal cells, which were consistent with previous studies . Aromatic‐turmerone administration could reverse this pathological change.…”

Section: Discussionsupporting

confidence: 90%

Aromatic‐Turmerone Attenuates LPS‐Induced Neuroinflammation and Consequent Memory Impairment by Targeting TLR4‐Dependent Signaling Pathway

Chen

Chang

Huang

et al. 2018

Molecular Nutrition Food Res

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Section: Discussionsupporting

confidence: 90%

Aromatic‐Turmerone Attenuates LPS‐Induced Neuroinflammation and Consequent Memory Impairment by Targeting TLR4‐Dependent Signaling Pathway

Chen

Chang

Huang

et al. 2018

Molecular Nutrition Food Res

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“…Though there is still no information on whether APN can regulate microglia activation, a recent report has demonstrated that microglia expressed adiponectin receptors. Osmotin, plant homolog of adiponectin, inhibited Toll-like receptor 4 (TLR4) in microglia cell line BV2 through AdipoR1 to prevent LPS-induced inflammation [49]. Moreover, astrocytes and macrophages also possess APN receptors and being stimulated by APN, suggesting that APN can regulate both cerebral and peripheral inflammation [50, 51].…”

Section: Discussionmentioning

confidence: 99%

Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice

Cheng

Jian

et al. 2016

Mol Neurodegeneration

140

137

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BackgroundInsulin resistance is the major pathogenesis underlying type 2 diabetes mellitus (T2DM) and these patients have doubled risk of Alzheimer’s disease (AD). Increasing evidence suggests that insulin resistance plays an important role in AD pathogenesis, possibly due to abnormal GSK3β activation, causing intra- and extracellular amyloid-beta (Aβ) accumulation. Adiponectin (APN) is an adipokine with insulin-sensitizing and anti-inflammatory effects. Reduced circulatory APN level is associated with insulin resistance and T2DM. The role of APN in AD has not been elucidated. In this study, we aim to examine if adiponectin deficiency would lead to cerebral insulin resistance, cognitive decline and Alzheimer’s-like pathology in mice.MethodsTo study the role of adiponectin in cognitive functions, we employed adiponectin-knockout (APN-KO) mice and demonstrated chronic APN deficiency in their CNS. Behavioral tests were performed to study the cognitions of male APN-KO mice. Brains and tissue lysates were collected to study the pathophysiological and molecular changes in the brain of APN-KO mice. SH-SY5Y neuroblastoma cell line was used to study the molecular mechanism upon APN and insulin treatment.ResultsAged APN-deficient mice displayed spatial memory and learning impairments, fear-conditioned memory deficit as well as anxiety. These mice also developed AD pathologies including increased cerebral Aβ42 level, Aβ deposition, hyperphosphorylated Tau proteins, microgliosis and astrogliosis with increased cerebral IL-1β and TNFα levels that associated with increased neuronal apoptosis and reduced synaptic proteins levels, suggesting APN deficiency may lead to neuronal and synaptic loss in the brain. AD pathologies-associated APN-KO mice displayed attenuated AMPK phosphorylation and impaired insulin signaling including decreased Akt induction and increased GSK3β activation in the hippocampus and frontal cortex. Aged APN-KO mice developed hippocampal insulin resistance with reduced pAkt induction upon intracerebral insulin injection. Consistently, APN treatment in SH-SY5Y cells with insulin resistance and overexpressing Aβ induce higher pAkt levels through AdipoR1 upon insulin treatment whereas the induction was blocked by compound C, indicating APN can enhance neuronal insulin sensitivity through AMPK activation.ConclusionOur results indicated that chronic APN deficiency inactivated AMPK causing insulin desensitization and elicited AD-like pathogenesis in aged mice which also developed significant cognitive impairments and psychiatric symptoms.Electronic supplementary materialThe online version of this article (doi:10.1186/s13024-016-0136-x) contains supplementary material, which is available to authorized users.

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“…It is likely therefore that immunohistochemistry is not sensitive enough to detect the basal cellular expression of TLR4. Moreover, in vitro experiments demonstrated that LPS can rapidly induce TLR4 in both CNS and non CNS cell types [61-63]. …”

Section: Discussionmentioning

confidence: 99%

Neuroinflammation Alters Integrative Properties of Rat Hippocampal Pyramidal Cells

et al. 2018

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Neuroinflammation is consistently found in many neurological disorders, but whether or not the inflammatory response independently affects neuronal network properties is poorly understood. Here, we report that intracerebroventricular injection of the prototypical inflammatory molecule lipopolysaccharide (LPS) in rats triggered a strong and long lasting inflammatory response in hippocampal microglia associated with a concomitant up-regulation of Toll-like receptor (TLR4) in pyramidal and hilar neurons. This, in turn, was associated with a significant reduction of the dendritic hyperpolarization-activated cyclic-AMP gated channel type 1 (HCN1) protein level while Kv4.2 channels were unaltered as assessed by western blot. Immunohistochemistry confirmed the HCN1 decrease in CA1 pyramidal neurons and showed that these changes were associated with a reduction of TRIP8b, an auxiliary subunit for HCN channels implicated in channel subcellular localization and trafficking. At the physiological level, this effect translated into a 50% decrease in HCN1-mediated currents (Ih) measured in the distal dendrites of hippocampal CA1 pyramidal cells. At the functional level, the band-pass filtering properties of dendrites in the theta frequency range (4-12 Hz) and their temporal summation properties were compromised. We conclude that neuroinflammation can independently trigger an acquired channelopathy in CA1 pyramidal cell dendrites that alters their integrative properties. By directly changing cellular function, this phenomenon may participate in the phenotypic expression of various brain diseases.

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Osmotin attenuates LPS-induced neuroinflammation and memory impairments via the TLR4/NFκB signaling pathway

Cited by 196 publications

References 52 publications

Aromatic‐Turmerone Attenuates LPS‐Induced Neuroinflammation and Consequent Memory Impairment by Targeting TLR4‐Dependent Signaling Pathway

Aromatic‐Turmerone Attenuates LPS‐Induced Neuroinflammation and Consequent Memory Impairment by Targeting TLR4‐Dependent Signaling Pathway

Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice

Neuroinflammation Alters Integrative Properties of Rat Hippocampal Pyramidal Cells

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