Minocycline protects against lipopolysaccharide-induced cognitive impairment in mice

Hou, Yue; Xie, Guanbo; Liu, Xia; Li, Guoxun; Jia, Congcong; Xu, Jinghua; Wang, Bing

doi:10.1007/s00213-015-4169-6

Cited by 56 publications

(28 citation statements)

References 62 publications

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“…Male Swiss–Kunming mice (18–22 g) were obtained from the Experimental Animal Center of Shenyang Pharmaceutical University and the permission number was SYPU‐IACUC‐C2017‐6‐30‐103. The animals were kept as previously described . Experimental procedures were performed in strict compliance with the Regulation of Experimental Animal Administration from the State Committee of Science and Technology of the People's Republic of China.…”

Section: Methodsmentioning

confidence: 99%

A Novel Quinolyl‐Substituted Analogue of Resveratrol Inhibits LPS‐Induced Inflammatory Responses in Microglial Cells by Blocking the NF‐κB/MAPK Signaling Pathways

Hou

Zhang

et al. 2019

Molecular Nutrition Food Res

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Scope The anti‐neuroinflammatory effect of a novel quinolyl‐substituted analogue of resveratrol (RV01) on lipopolysaccharide (LPS)‐induced microglial activation is investigated, as well as the possible underlying mechanisms. Methods and results Cell viability is measured using an MTT assay. Nitric oxide (NO) release is determined by nitrite assay. The interaction between RV01 and inducible nitric oxide synthase (iNOS) is studied using molecular docking. Free radical scavenging activity and reactive oxygen species (ROS) production are determined by DPPH reduction assay and DCFH‐DA assay. Pretreatment with RV01 (1–30 µm) prior to LPS (1 µg mL–1) stimulation decreased NO release and iNOS expression without observable cytotoxicity. RV01 reduced the mRNA levels and secretion of tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). RV01 also inhibited LPS‐induced ROS production and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. Furthermore, RV01 decreases the protein expression of toll‐like receptor 4 (TLR4) and inhibits the LPS‐induced activation of the mitogen‐activated protein kinase (MAPK) and nuclear transcription factor‐κB (NF‐κB) signaling pathways. Additionally, conditioned medium from microglia co‐treated with LPS and RV01 alleviates the death of SH‐SY5Y cells induced by conditioned medium from activated N9 microglial cells. Lastly, a mouse neuroinflammation model is further used to confirm the effect of RV01 in vivo. Conclusion These results show that RV01 suppresses microglia‐mediated neuroinflammation and protects neurons from inflammatory damage, which indicates that RV01 has great potential as a nutritional preventive strategy for neuroinflammation‐related diseases.

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Section: Methodsmentioning

confidence: 99%

A Novel Quinolyl‐Substituted Analogue of Resveratrol Inhibits LPS‐Induced Inflammatory Responses in Microglial Cells by Blocking the NF‐κB/MAPK Signaling Pathways

Hou

Zhang

et al. 2019

Molecular Nutrition Food Res

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“…Additionally, we explored brain brain-derived neurotrophic factor (BDNF) levels. In the aging brain and under neuroinflammatory conditions, BDNF levels are reduced secondary to the M1 polarization of microglia and proinflammatory astrocytes [51][52][53][54]. The two-way ANOVA showed that administration of LPS modified the brain BDNF levels (F 2, 21 = 6:85; P = 0:0051) as well as MPTP (F 1, 21 = 69:57; P < 0:0001).…”

Section: Mptp Intoxication After Systemic Inflammationmentioning

confidence: 96%

Chronic Systemic Inflammation Exacerbates Neurotoxicity in a Parkinson’s Disease Model

Ugalde‐Muñiz

Fetter-Pruneda

Navarro

et al. 2020

Oxidative Medicine and Cellular Longevity

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Systemic inflammation is a crucial factor for microglial activation and neuroinflammation in neurodegeneration. This work is aimed at assessing whether previous exposure to systemic inflammation potentiates neurotoxic damage by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and how chronic systemic inflammation participates in the physiopathological mechanisms of Parkinson’s disease. Two different models of systemic inflammation were employed to explore this hypothesis: a single administration of lipopolysaccharide (sLPS; 5 mg/kg) and chronic exposure to low doses (mLPS; 100 μg/kg twice a week for three months). After three months, both groups were challenged with MPTP. With the sLPS administration, Iba1 staining increased in the striatum and substantia nigra, and the cell viability lowered in the striatum of these mice. mLPS alone had more impact on the proinflammatory profile of the brain, steadily increasing TNFα levels, activating microglia, reducing BDNF, cell viability, and dopamine levels, leading to a damage profile similar to the MPTP model per se. Interestingly, mLPS increased MAO-B activity possibly conferring susceptibility to MPTP damage. mLPS, along with MPTP administration, exacerbated the neurotoxic effect. This effect seemed to be coordinated by microglia since minocycline administration prevented brain TNFα increase. Coadministration of sLPS with MPTP only facilitated damage induced by MPTP without significant change in the inflammatory profile. These results indicate that chronic systemic inflammation increased susceptibility to MPTP toxic effect and is an adequate model for studying the impact of systemic inflammation in Parkinson’s disease.

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“…Minocycline, a bacteriostatic antibiotic and immunomodulator, readily crosses the blood brain barrier and inhibits microglial activation and proliferation 20 . Its administration effectively restores cognition in rodent models of chronic stress 21 , cranial irradiation 22 , aging 23 , and systemic bacterial infection 24 . Here, we sought to determine whether minocycline was also an effective treatment for spatial recognition memory impairments in rats fed a cafeteria diet.…”

Section: Introductionmentioning

confidence: 99%

Minocycline-induced microbiome alterations predict cafeteria diet-induced spatial recognition memory impairments in rats

et al. 2020

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Diets rich in sugar and saturated fat are associated with cognitive impairments in both humans and rodents with several potential mechanisms proposed. To test the involvement of diet-induced pro-inflammatory signaling, we exposed rats to a high-fat, high-sugar cafeteria diet, and administered the anti-inflammatory antibiotic minocycline. In the first experiment minocycline was coadministered across the diet, then in a second, independent cohort it was introduced following 4 weeks of cafeteria diet. Cafeteria diet impaired novel place recognition memory throughout the study. Minocycline not only prevented impairment in spatial recognition memory but also reversed impairment established in rats following 4 weeks cafeteria diet. Further, minocycline normalized diet-induced increases in hippocampal pro-inflammatory gene expression. No effects of minocycline were seen on adiposity or dietary intake across the experiments. Cafeteria diet and minocycline treatment significantly altered microbiome composition. The relative abundance of Desulfovibrio_OTU31, uniquely enriched in vehicle-treated cafeteria-fed rats, negatively and significantly correlated with spatial recognition memory. We developed a statistical model that accurately predicts spatial recognition memory based on Desulfovibrio_OTU31 relative abundance and fat mass. Thus, our results show that minocycline prevents and reverses a dietary-induced diet impairment in spatial recognition memory, and that spatial recognition performance is best predicted by changes in body composition and Desulfovibrio_OTU31, rather than changes in pro-inflammatory gene expression.

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Minocycline protects against lipopolysaccharide-induced cognitive impairment in mice

Cited by 56 publications

References 62 publications

A Novel Quinolyl‐Substituted Analogue of Resveratrol Inhibits LPS‐Induced Inflammatory Responses in Microglial Cells by Blocking the NF‐κB/MAPK Signaling Pathways

A Novel Quinolyl‐Substituted Analogue of Resveratrol Inhibits LPS‐Induced Inflammatory Responses in Microglial Cells by Blocking the NF‐κB/MAPK Signaling Pathways

Chronic Systemic Inflammation Exacerbates Neurotoxicity in a Parkinson’s Disease Model

Minocycline-induced microbiome alterations predict cafeteria diet-induced spatial recognition memory impairments in rats

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