The Study Of EPA Regulates Brain-derived Neurotrophic Factor Expression Against Neuronal Injury Induced By Interleukin-1?

BackgroundAlzheimer's disease(AD)is a high-grade neurodegenerative disease in the elderly,although its specific pathogenesis is still unclear.However,numerous studies have shown that neuroinflammation plays an important role in the process of degeneration and damage of AD neurons.Therefore,improving the pathology of neuroinflammation will certainly be beneficial to the prevention and treatment of AD.Eicosapentaenoic acid(EPA)is a polyunsaturated fatty acid(PUFAs)that cannot be synthesized by the human body.The reduction in intake was positively correlated with high AD,suggesting that EPA has the potential to protect neurons from AD.So is the anti-AD effect of EPA's neuroprotection related to improving inflammatory pathology?In a previous study,the team reported that EPA can alleviate inflammation-induced neuronal damage,and this effect is associated with EPA reversing the down-regulation of inflammation-induced brain-derived neurotrophic factor(BDNF)expression.However,how EPA interferes with the expression of BDNF in inflammatory conditions is currently unclear.Studies have shown that cAMP response element binding protein(CREB)is involved in the regulation of BDNF expression,and CREB can up-regulate BDNF expression by binding to upstream regulatory elements of BDNF structural gene.Before the initiation of CREB function,mitogen-activated protein kinase(MAPK)or Akt,protein kinase A(PKA)and other proteases are required to phosphorylate CREB serine 133 sites to make them inactive.The state is activated by activation.Studies have found that EPA affects the activity of various kinases including Akt kinase.Therefore,this study speculated that EPA may affect the expression of BDNF by interfering with Akt expression,which in turn affects the activation of CREB phosphorylation,and ultimately improves the effects of inflammation-related AD neuron damage.To validate the above hypothesis,this study used primary cultured hippocampal neurons to induce inflammatory neuronal damage with interleukin-1 beta(IL-1?),followed by EPA intervention and binding to specific Akt signals.Blocking,detecting the changes of BDNF expression under different conditions,analyzing the relationship between EPA and AD-related inflammatory neuron injury and BDNF,and exploring the possible signaling pathway of EPA intervention in inflammatory conditions,which is a potential clinical AD prevention treatment for EPA.The application provides theoretical support.The study used IL-1? because IL-1? is the central factor driving AD inflammatory pathology,and its central inflammation can accurately reflect the inflammatory pathological changes of AD.Method:SD rats were sacrificed for 18 days,and hippocampal neurons were cultured aseptically.After 7 days of continuous culture,inflammatory cell damage was induced by IL-1?,EPA intervention was performed,and Akt signaling specific antagonist was used to repress Akt signaling.The activity of neurons was detected by MTT assay under different treatment conditions.The expression of BDNF mRNA was detected by real time-PCR.The expressions of BDNF,Akt,p-Akt,CREB and p-CREB were detected by western blot.Results:1.Treatment of hippocampal neurons with different concentrations of IL-1?,MTT results showed that IL-1? induced dose-dependent hippocampal neuronal damage;while EPA co-incubation significantly inhibited IL-1?-induced decrease in cell viability,showing significant Anti-inflammatory neuronal damage effect;2.Western Blot and real-time PCR showed that IL-1? down-regulated the expression of BDNF in hippocampal neurons and inhibited the phosphorylation of Akt and CREB.Under the action of EPA,the expression of BDNF and the inhibition of Akt and CREB phosphorylation were all inhibited.Improved,suggesting that the neuroprotective effects of EPA are associated with BDNF expression regulation;3.Akt signaling was antagonized by Akt-specific antagonist KRX-0401.MTT results showed that the effect of EPA on IL-1? neuron injury was significantly weakened,suggesting that the neuroprotective effect of EPA is involved in Akt signaling;4.Akt-specific antagonist KRX-0401 antagonizes Akt signaling.Western blot results showed that IL-1?-mediated down-regulation of BDNF and inhibition of Akt/CREB phosphorylation were all antagonized by EPA.It is suggested that the Akt/CREB signaling pathway is involved in the regulation of BDNF expression by EPA.Conclusions:1.IL-1?mediates inflammatory neuronal injury,which is related to IL-1?inhibiting Akt/CREB phosphorylation activation and down-regulating BDNF expression;2.EPA against IL-1?-induced down-regulation of BDNF expression,showing significant anti-inflammatory neuronal damage effects;3.Akt/CREB signaling pathway participates in the regulation of BDNF expression by EPA.