Acrylamide inhibits long-term potentiation and learning involving microglia and pro-inflammatory signaling.
Acrylamide inhibits long-term potentiation and learning involving microglia and pro-inflammatory signaling.
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DOI：
10.1038/s41598-022-16762-7
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发表时间：
2022-07-20
影响因子：
4.6
通讯作者：
Zorumski, Charles F.
中科院分区：
文献类型：
--
作者：
Izumi, Yukitoshi;Fujii, Chika;O'Dell, Kazuko A.;Zorumski, Charles F.
丙烯酰胺是一种用于各种行业的化学品，也是含有天冬酰胺的蔬菜高温烹饪后的产物。环境或饮食暴露于丙烯酰胺可能会损害认知功能，因为它的神经毒性。使用大鼠海马脑片，我们测试丙烯酰胺是否会改变长时程增强（LTP）的诱导，这是一种学习和记忆的细胞模型。我们假设丙烯酰胺通过激活促炎细胞因子损害认知功能，因为已经报道了NLRP 3炎性体的强烈上调。尽管丙烯酰胺浓度高达3 mM时并不改变基础突触传递，但与10 μM孵育或急性给予100 μM丙烯酰胺可抑制LTP的诱导。Toll样受体4（TLR 4）的抑制剂和米诺环素（一种小胶质细胞活化的抑制剂）克服了丙烯酰胺对LTP诱导的影响。此外，我们观察到，丙烯酰胺不能抑制LTP后，管理的MCC 950，NLRP 3的抑制剂，或在存在白细胞介素-1受体拮抗剂（IL-1 Ra）。我们还发现，在体内丙烯酰胺注射短暂受损的体重增加和受损的一次试验抑制性回避学习。这种学习缺陷被MCC 950克服了。这些结果表明，丙烯酰胺引起的认知障碍是由涉及小胶质细胞和通过NLRP 3激活释放细胞因子的机制介导的。
Acrylamide is a chemical used in various industries and a product following high-temperature cooking of vegetables containing asparagine. Environmental or dietary exposure to acrylamide could impair cognitive function because of its neurotoxicity. Using rat hippocampal slices, we tested whether acrylamide alters induction of long-term potentiation (LTP), a cellular model of learning and memory. We hypothesized that acrylamide impairs cognitive function via activation of pro-inflammatory cytokines because robust upregulation of NLRP3 inflammasome has been reported. Although acrylamide up to 3 mM did not alter basal synaptic transmission, incubation with 10 μM or acute administration of 100 μM acrylamide inhibited induction of LTP. Inhibitors of toll-like receptor 4 (TLR4), and minocycline, an inhibitor of microglial activation, overcame the effects of acrylamide on LTP induction. Furthermore, we observed that acrylamide failed to inhibit LTP after administration of MCC950, an inhibitor of NLRP3, or in the presence of Interleukin-1 receptor antagonist (IL-1Ra). We also found that in vivo acrylamide injection transiently impaired body weight gain and impaired one-trial inhibitory avoidance learning. This learning deficit was overcome by MCC950. These results indicate that cognitive impairment by acrylamide is mediated by mechanisms involving microglia and release of cytokines via NLRP3 activation.
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影响因子：
9.3
作者：
Leow-Dyke S;Allen C;Denes A;Nilsson O;Maysami S;Bowie AG;Rothwell NJ;Pinteaux E
通讯作者：
Pinteaux E
影响因子：
4.7
作者：
Hanamsagar R;Torres V;Kielian T
通讯作者：
Kielian T
影响因子：
24
作者：
Onat, Umut I.;Yildirim, Asli D.;Erbay, Ebru
通讯作者：
Erbay, Ebru
影响因子：
15.1
作者：
Alcocer-Gomez, Elisabet;de Miguel, Manuel;Cordero, Mario D.
通讯作者：
Cordero, Mario D.
影响因子：
32.4
作者：
Gaidt, Moritz M.;Ebert, Thomas S.;Hornung, Veit
通讯作者：
Hornung, Veit