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Lomerizine regulates LPS-induced neuroinflammation and tau phosphorylation in vivo

Lomerizine regulates LPS-induced neuroinflammation and tau phosphorylation in vivo
Jinhee Park
DGIST Authors
Jinhee ParkJinsoo SeoHyang-Sook Hoe
Hyang-Sook Hoe
Issued Date
Awarded Date
"Lomerizine"; "neuroinflammation"; "tauopathy"; "DYRK1A"; "NLRP3"
Lomerizine is a calcium channel blocker that crosses the blood–brain barrier and is used clinically in the treatment of migraines. Whether lomerizine also plays a beneficial role in modulating neuroinflammatory responses is still unknown. To address this gap, the effects of lomerizine on LPS-induced proinflammatory responses were investigated in vitro and in vivo. In this study found that lomerizine significantly reduced the LPS-evoked upregulation of IL-1, IL-6, and NLRP3 transcription in BV2 microglial cells. In the brains of wild-type mice, lomerizine significantly suppressed the LPS-induced expression of Iba-1 and GFAP, microglial and astrocyte proliferation, proinflammatory cytokine upregulation, and NLRP3 inflammasome activation. And, also observed protective effects of lomerizine against tau pathology in LPS-treated wild-type mice. Finally, this found that lomerizine abolished the LPS-mediated activation of GSK3b and upregulation of DYRK1A, which is responsible for tau phosphorylation, in the brain in wild-type mice. Taken together, these data suggest that lomerizine attenuates LPS-mediated neuroinflammatory responses and tau pathology and is a potential drug for neuroinflammation- or tauopathy-associated diseases|Lomerizine은 혈액-뇌 장벽을 통과하는 칼슘 채널 차단제이며 편두통 치료에 임상적으로 사용된다. 현재까지 Lomerizine 신경 염증 반응을 조절하는 데에도 유익한 역할을 하는지 여부는 알려져 있지 않다. 이를 해결하기위해 LPS로 유도된 염증 반응에 대한 로메리진의 영향을 세포실험 및 동물실험을 통해 알아보았으며 세포실험 결과 Lomerizin이 미세아교세포 BV2 세포에서IL-1, IL-6 및 NLRP3 전사의 LPS 유발 조절을 크게 감소시킨다는 것을 발견했다. 동물실험 결과 쥐의 뇌에서, Lomerizine은 Iba-1과 GFAP의 LPS 유도 발현, 미세아교세포 및 별아교세포 증식, 전염증성 사이토카인 상향조절, NLRP3 인플라마좀 활성화를 유의하게 억제했다.
LPS 처리 쥐에서 타우 병리학에 대한 Lomerizine의 보호 효과를 관찰한 결과, 쥐의 뇌에서 LPS 매개 활성화와 타우 인산화를 담당하는 DYRK1A의 상향 조절이 LPS 매개 활성화를 폐지했다는 것을 발견하였으며 타우 병리에 대한 로메리진의 보호 효과를 관찰했다. 종합하면, 이러한 데이터는 LPS 매개 신경염증 반응 및 타우 병리학을 약화시키고 신경염증 또는 타우병증 관련 질병에 대한 잠재적인 약물임을 제시한다.
Table Of Contents
Ⅰ. Introduction 1
1.1 Introduction 1

II. Materials and Methods 3
2.1 Ethics Statement 3
2.2 Lomerizine 3
2.3 Cell culture 3
2.4 MTT 3
2.5 Real-time PCR 3
2.6 Wild-type mice 4
2.7 Treatment of wild-type mice with lomerizine 4
2.8 Immunofluorescent staining 4
2.9 Statistical analysis 5

III. Results 6
3.1 Lomerizine downregulates LPS-evoked proinflammatory cytokine and NLRP3 levels in BV2 microglial cells. 6
3.2 Lomerizine suppresses the LPS-induced expression of Iba-1 and GFAP and the proliferation of microglia and astrocytes in wild-type mice 8
3.3 Lomerizine diminishes the LPS-induced upregulation of the proinflammatory cytokines IL-6 and IL-1 in wild-type mice 11
3.4 Lomerizine decreases NLRP3 inflammasome activation in LPS-treated wild-type mice 14
3.5 Lomerizine suppresses LPS-induced tau phosphorylation in wild-type mice 16
3.6 Lomerizine inhibits the LPS-induced activation of the tau kinases GSK3and DYRK1A in vivo 19

IV. Discussion 22
4.1 Discussion 22

V. Conclusion 25
5.1 Conclusion 25

Ⅵ. References 26
6.1 References 26
Department of Brain Sciences
Related Researcher
  • 서진수 Seo, Jinsoo 뇌과학과
  • Research Interests iPSC; Alzheimer's disease; Neurodegeneration; Synapse; Neuroscience
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