Neuroprotective effect of sodium ferulate and signal transduction mechanisms in the aged rat hippocampus1

• Published in: Acta pharmacologica Sinica Vol. 29; no. 12; pp. 1399 - 1408
• Main Authors: JIN, Ying, YAN, En‐zhi, LI, Xiao‐ming, FAN, Ying, ZHAO, Yan‐jie, LIU, Zhuo, LIU, Wan‐zhu
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2008
• Subjects: c‐Jun N‐terminal kinases; extracellular signal‐regulated kinase; ferulic acid; interleukin‐1β; proto‐oncogene proteins c‐akt
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1111/j.1745-7254.2008.00848.x

Aim: To investigate whether the age‐related increase in interleukin‐1β (IL‐1β) and c‐Jun N‐terminal kinases (JNK) pathway was coupled with a decrease in cell survival signaling pathways and whether sodium ferulate (SF) treatment was effective in preventing these age‐associated changes. Methods: Groups of young and aged rats were fed for 4 weeks on a diet enriched in SF (100 mg/kg and 200 mg/kg per day). At the end of the period of dietary manipulation, Western blotting analysis was used to determine the expressions of IL‐1β, phosphorylated mitogen‐activated protein kinase kinase (MKK)4, phospho‐JNK, phospho‐c‐Jun, phosphorylated extracellular signal‐regulated kinase (ERK1/2), phospho‐MEK, phospho‐Akt, phosphorylated ribosomal protein S6 protein kinase (p70S6K), and activated caspase‐3 and caspase‐7. Nissl staining was used to observe the morphological change in hippocampal CA1 regions. Immunohistochemical techniques for glial fibrillary acidic protein (GFAP) and integrin αM (OX‐42) were used to determine the astrocyte and microglia activation. Results: IL‐1β protein levels, and phospho‐MKK4, phospho‐JNK1/2, and phospho‐c‐Jun were significantly enhanced in hippocampus prepared from age‐matched control rats. Increased IL‐1β production and JNK1/2 activation was accompanied by down‐regulation of MEK/ERK1/2 pathway and Akt/p70S6K pathway, leading to cell apoptosis assessed by activation of caspase‐3. Significantly, treatment of aged rats with SF (100 mg/kg and 200 mg/kg per day) for 4 weeks prevented the age‐related increase in IL‐1β and IL‐1β‐induced JNK signaling pathway and also the age‐related changes in ERK and Akt kinase. Conclusion: SF plays neuroprotective roles through suppression of IL‐1β and IL‐1β‐induced JNK signaling and upregulation of MEK/ERK1/2 and Akt/p70S6K survival pathways.