Effect of Celastrol on cognitive function and Tau hyperphosphorylation in eldly mice hippocampus after partial hepatectomy

Abstract

Abstract: AIM: To observe the expression of Tau phosphorylation in hippocampus and cognitive function deficit on eldly mice induced by partial hepatectomy. As well as the neuroprotective effect of Celastrol on postoperative cognitive dysfunction.METHODS: The C57BL/6 eldly mice were randomly assigned to three groups (n =48): Sham operation group (group S),operation group (group O) underwent partial hepatectomy and the Celastrol treatment was given to the operation group (group C). According to the different time point,each group(n=12) was divided 12 h,1,3 and 7 d,respectively. The cognitive function in three groups was detected by Morris water maze test;the changes of Tau phosphorylation were measured by immunocytochemistry/Western blotting.RESULTS: Compared with the Group S, the results of the Morris water maze test were significantly decreased in Group O at 3, 7 d (P<0.05); compared with Group O,the results of the Morris water maze test in Group C were obviously increased (P<0.05), approached the Group S (P>0.05). Compared with Group S,the immunochemistry staining of brain slice and Western blotting showed that the expressions of Tau pSer404, pSer199/202 in Group O were markedly increased (P<0.01). The level of Tau hyperphosphorylation in Group C was markedly decreased comparing to those in Group O (P<0.01) and approached the Group S (P>0.05).CONCLUSION: Celastrol can improve cognitive dysfunction induced by partial hepatectomy in eldly mice, the mechanism is correlated with Tau hyperphosphorylation inhibited.

Key words: Partial hepatectomy, Tau protein, Phosphorylation, Cognitive function, Celastrol

CLC Number:

R965.2

GE Ye-ying, WAN Yan-jie, XU Jing, MENG Fan-zhen. Effect of Celastrol on cognitive function and Tau hyperphosphorylation in eldly mice hippocampus after partial hepatectomy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(8): 841-846.

References

[1] Guillozet AL,Weintraub S,Mash DC,et al.Neurofibrillary tangles.amyloid,and memory in aging and mild cognitive impairment[J].Arch Neurol,2003,60(5):729-736.
[2] Hyo WJ,Yoo SC,Yoon SK,et al.Celastrol inhibits production of nitric oxide and proinflammatory cytokines through MAPK signal transduction and NF-κB in LPS-stimulated BV-2 microglial cells[J]. Exp Mol Med,2007,39(6):715-721.
[3] 张艳,贾丹辉,刘宗文,等.雷公藤对大鼠局灶性脑缺血再灌注损伤的保护作用[J].中国新药与临床杂志,2005,24(5):862-864.
[4] 吴周全,万燕杰,曾因明,等.肝部分切除术后大鼠认知功能及β淀粉样蛋白的变化[J].中华麻醉学杂志,2008,28(4):334-336.
[5] Tian Q,Wang J. Role of serine/threonine protein phosphatase in Alzheimer's disease[J]. Neurosignals,2002,11(5):262-269.
[6] Wan YJ,Xu J,Ma DQ,et al. Postoprative impairment of cognitive function in rats-Apossible role for cytokine-mediated inflammation in the hippocampus[J]. Anesthesiology,2007,107(5):436-443.
[7] 段立晖,周国庆,夏树开,等.β淀粉样蛋白诱导大鼠海马神经元Tau蛋白异常磷酸化及雌激素的保护作用[J].医学研究生学报,2008,21(5):486-490.
[8] Tuppoa EE,Ariasb HR.The role of inflammation in Alzheimerps disease[J].Int J Biochem Cell Biol,2005,37(5):289-305.
[9] Li YK,Liu L,Barger SW,et al.Interleukin-1 mediates pathological effects of microglia on Tau phosphorylation and on synap tophysin synthesis in cortical neurons through a p38-MAPK pathway[J].J Neurosci,2003,23(5):1605-1611.
[10] 黄秀旺,许建华,陈元仲.雷公藤内酯醇在大鼠体内的组织分布[J].中国临床药理学与治疗学,2008,13(7):764-767.
[11] Allison AC,Cacabelos R,Lombardi VR,et al. Celastrol,a potent antioxidant andanti-inflammatory drug, as a possible treatment for Alzheimer's disease[J]. Prog Neuropsychopharmacol Biol Psychiatry,2001,25(7):1341-1357.
[12] Liu SJ,Zhang AH,Li HL,et al.Overactivation of glycogen synthase kinase-3 by inhibition of phosphoinositol-3 kinase and protein kinase C leads to hyperphosphorylation of Tau and impairment of spatial memory[J].Neurochem,2003,87(6):1333-1344.
[13] Sandy DW,Joshua DB,Bessie NA,et al. Celastrols as inducers of the heat shock response and cytoprotection[J]. J Biol Chem,2004,279(53):56053-56060.
[14] Ari MC,Ian R.Induction of heat shock proteins in differentiated human and rodent neurons by celastrol[J].Cell Stress Society Internation,2007,12(3):237-244.
[15] Trott A,James DW,Sandy DW,et al.Activation of heat shock and antioxidant responses by the natural product celastrol: transcriptional signaturesof a thiol-targeted molecule[J]. Mol Biol Cell,2008,19(3):1104-1112.