Sodium ferulate prevents amyloid-beta-induced neurotoxicity through suppression of p38 MAPK and upregulation of ERK-1/2 and Akt/protein kinase B in rat hippocampus1

Abstract

Aim: To observe whether an amyloid β (Aβ)-induced increase in interleukin (IL)-1β was accompanied by an increase in the p38 mitogen-activated protein kinase (MAPK) pathway and a decrease in the cell survival pathway, and whether sodium ferulate (SF) treatment was effective in preventing these Aβ-induced changes. Methods: Rats were injected intracerebroventricularly with Aβ [25][26][27][28][29][30][31][32][33][34][35] . Seven days after injection, immunohistochemical techniques for glial fibrillary acidic protein (GFAP) were used to determine the astrocyte infiltration and activation in hippocampal CA1 areas. The expression of IL-1β, extracellular signal-regulated kinase (ERK), p38 MAPK, Akt/protein kinase B (PKB), Fas ligand and caspase-3 were determined by Western blotting. The caspase-3 activity was measured by cleavage of the caspase-3 substrate (Ac-DEVD-pNA). Reverse transcriptionpolymerase chain reaction was used to analyze the changes in IL-1βmRNA levels. Results:Intracerebroventricular injection of Aβ 25-35 elicited astrocyte activation and infiltration and caused a strong inflammatory reaction characterized by increased IL-1β production and elevated levels of IL-1β mRNA. Increased IL-1β synthesis was accompanied by increased activation of p38 MAPK and downregulation of phospho-ERK and phospho-Akt/PKB in hippocampal CA regions prepared from Aβ-treated rats, leading to cell death as assessed by activation of caspase-3. SF significantly prevented Aβ-induced increases in IL-1β and p38 MAPK activation and also Aβ-induced changes in phospho-ERK and phospho-Akt/PKB expression levels. Conclusion: SF prevents Aβ-induced neurotoxicity through suppression of p38 MAPK activation and upregulation of phospho-ERK and phospho-Akt/PKB expression.

Atorvastatin prevents amyloid-β peptide oligomer-induced synaptotoxicity and memory dysfunction in rats through a p38 MAPK-dependent pathway

“…Activated p38MAPK is observed in human AD brain tissue [57] and in AD-relevant animal models [58,59] , and cell culture studies strongly implicate p38MAPK in the increased production of proinflammatory cytokines in the glia activated by Aβ [60] . The activation of p38MAPK in neuronal cells has been associated with IL-1 and hyperphosphorylated tau in AD [61] .…”

Phenolic acids from malt are efficient acetylcholinesterase and butyrylcholinesterase inhibitors

“…Sodium ferulate restored the arrangement and the number of hippocampal CA1 pyramidal neurons in the hippocampus of young adult rats subjected to b-amyloid-(1-40) (67) as well as the arrangement of hippocampal CA1 pyramidal neurons in the hippocampus of aged rats (68). This ferulic acid salt has also been shown to significantly inhibit b-amyloid-induced astrocyte activation and inflammation and suppress the increase in caspase-3 activity and expression of caspase-3 protein in the rat hippocampus (66,68). It has been demonstrated (69) that sinapic acid and its derivatives tenuifoliside B and 3,6′-disinapoylsucrose inhibited KCN-induced hypoxia and scopolamine-and CO 2 -induced memory impairment in mice.…”

“…Sodium ferulate partly reduced the decrease in phosphorylated extracellular signal-regulated kinases ERK1 and ERK2 and completely reversed the decrease in phosphorylated Akt/protein kinase B induced by b-amyloid- (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) in the hippocampal regions of the rat brain (66). Also, sodium ferulate inhibited a b-amyloid-(1-40)-induced increase in phosphorylated-p38 mitogen-activated protein kinase (MKK3/MKK6), partly prevented a decrease in phosphorylated MAPKAPK2 and Hsp27 expression, and inhibited the activation of caspase cascades (caspase-3, caspase-7 and caspase-3 activities) (67).…”

Osthole Reverses Beta-Amyloid Peptide Cytotoxicity on Neural Cells by Enhancing Cyclic AMP Response Element-Binding Protein Phosphorylation

“…33,34) It has been confirmed that Aβ [25][26][27][28][29][30][31][32][33][34][35] can cause neural cell death, induced suppression of extracellular signal-regulated kinase (ERK) or its downstream intermediate CREB in neuroblastoma cells and in rats after injection of Aβ [25][26][27][28][29][30][31][32][33][34][35] . 35,36) In the present study, we thus used Aβ [25][26][27][28][29][30][31][32][33][34][35] to induce cytotoxicity in neurons and SH-SY5Y cells. It was found that Aβ [25][26][27][28][29][30][31][32][33][34][35] insult markedly decreased cell viability and synapsin-1 protein level …”