논문 (학술지)
beta-amyloid inhibits hippocampal LTP through TNFR/IKK/NF-kappa B pathway
| 등록번호 | RPMS-2019-0190732185 | SCI 구분
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※구분 : SCI(SCIE포함), 비SCI |
SCI |
|---|---|---|---|
| 저자명 (주·공동저자) | Samidurai Manikandan; Ramasamy Vijay S.; Jo Jihoon | ||
| 논문구분 | 국외전문학술지 | 학술지명 | NEUROLOGICAL RESEARCH |
| ISSN | 0161-6412 | 학술지 출판일자 | - |
| 학술지 볼륨번호 | 40 | 논문페이지 | 268 ~ 276 |
| 학술지 임팩트팩터 | 1.376 | 기여율 | 50 % |
| DOI | 10.1080/01616412.2018.1436872 | ||
| 초록 | Objective: The suppressive action of the acute application of oligomeric amyloid-β (Aβ) on hippocampal long-term potentiation (LTP) has been reported widely. Many mechanisms have been proposed for Aβ inhibited LTP induction. The inflammatory cytokine tumor necrosis factor-α (TNF-α) has also been reported to play a key role in this LTP inhibition through Aβ. However, the underlying molecular mechanisms are largely unknown. This study aimed to investigate the link between Aβ- and TNF-α-mediated hippocampal LTP inhibition. Methods: Acute hippocampal slices of male wildtype or Alzheimer’s disease (AD) transgenic mouse models were treated with the inhibitors of either TNF-α, IκB Kinase (IKK) or Nuclear Factor- κB (NF-κB) in the presence or absence of oligomeric Aβ42 (500 nM/2 h). The LTP was assessed using field excitatory post synaptic potential recordings (fEPSP), and immunoblotting was used to evaluate the expression of IKK and NF-κB. Results: Acute treatment with Aβ or TNF-α alone inhibited LTP and increased the phosphorylation of IKK and NF-κB in wild type mouse hippocampal slices. Pretreatment with TNF-α antagonist infliximab rescued the LTP impairment by Aβ and also restored the levels of IKK and NF-κB to the control levels. In addition, pretreatment with IKK2 IV or JSH23 also restored the Aβ-mediated LTP impairment. Furthermore, AD transgenic mouse hippocampal slices treated with infliximab or inhibitors of IKK or NF-κB showed improved LTP and reversed the activation of IKK and NF-κB. Conclusion: In conclusion, our observations suggest that the IKK/NF-κB signaling pathway play an important role in Aβ-mediated hippocampal LTP impairment. Aβ might modulate IKK/NF-κB activity by binding or activating tumor necrosis factor receptor (TNFR). Background Accumulation of extracellular deposits of amyloid-β (Aβ) is the hall mark of Alzheimer’s disease. Aβ is believed to be the causative factor of AD neuropathology [1]. Aβ causes memory impairment with several mechanisms such as activating apoptotic proteins (caspases) or inducing Reactive oxygen species (ROS) production [2,3]. Soluble Aβ isolated directly from AD patients alters synaptic plasticity by disrupting glutamatergic transmission [4]. Acute treatment of oligomeric Aβ disrupts hippocampal LTP by activating caspase-3, AKT8 virus oncogene cellular homolog (Akt), and Glycogen synthase kinase 3β (GSK-3β) pathway [5]. In a similar manner, soluble Aβ causes memory loss by altering the Janus kinase2 (JAK2) / Signal transducer and activator of transcription 3 (STAT3) axis and cholinergic dysfunction in the Tg2576 mouse model [6]. TNF-α is a cytokine and a major regulator of the inflammatory pathways. In addition to its role in neuroinflammation, several studies | ||
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