Effect of anti-dementia drugs on LPS induced neuroinflammation in mice

被引:48
作者
Tyagi, Ethika [1 ]
Agrawal, Rahul [1 ]
Nath, Chandishwar [1 ]
Shukla, Rakesh [1 ]
机构
[1] Cent Drug Res Inst, Div Pharmacol, Lucknow 226001, Uttar Pradesh, India
关键词
neuroinflammation; anti-dementia drugs; lipopolysaccharide; IL-2; acetylcholinesterase;
D O I
10.1016/j.lfs.2007.02.039
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Inflammation has been recently implicated in pathogenesis of dementia disorders. Effect of anti-dementia (Acetylcholinesterase inhibitor) drugs tacrine, rivastigmine and donepezil were studied on neuroinflammation induced by intraperitoneal administration of lipopolysaccharide (LPS) in mice. Interleukin-2 (IL-2) and isoforms of acetylcholinesterase (AChE) were estimated in different brain areas as marker for neuroinflammation and cholinergic activity respectively. LPS significantly increased the level of IL-2 in all the brain areas while enhancement of AChE activity varied in brain areas. It was found that administration of tacrine, rivastigmine and donepezil in mice significantly attenuated the LPS induced increased levels of IL-2 along with the significant reduction of AChE activity predominantly in salt soluble (SS) fraction as compared to the detergent soluble (DS) fraction in a dose dependent manner. In vitro effect of LPS was also studied in different brain areas. LPS significantly increased the AChE activity in SS fractions but the significant increase was not found in DS fractions. The present study indicate that cholinesterase inhibitor anti-dementia drugs are effective against LPS induced neuroinflammation that may be linked to enhanced cholinergic activity. (C) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:1977 / 1983
页数:7
相关论文
共 33 条
[21]   Anti-inflammatory properties of cholinergic up-regulation: A new role for acetylcholinesterase inhibitors [J].
Nizri, E ;
Hamra-Amitay, Y ;
Sicsic, C ;
Lavon, I ;
Brenner, T .
NEUROPHARMACOLOGY, 2006, 50 (05) :540-547
[22]   Cytokines and autoimmunity [J].
O'Shea, JJ ;
Ma, A ;
Lipsky, P .
NATURE REVIEWS IMMUNOLOGY, 2002, 2 (01) :37-45
[24]  
Pitossi F, 1997, J NEUROSCI RES, V48, P287, DOI 10.1002/(SICI)1097-4547(19970515)48:4<287::AID-JNR1>3.0.CO
[25]  
2-7
[26]   Acetylcholinesterase inhibitors reduce brain and blood interleukin-1β production [J].
Pollak, Y ;
Gilboa, A ;
Ben-Menachem, F ;
Ben-Hur, T ;
Soreq, H ;
Yirmiya, R .
ANNALS OF NEUROLOGY, 2005, 57 (05) :741-745
[27]   Treatment with an acetylcholinesterase inhibitor in Alzheimer patients modulates the expression and production of the pro-inflammatory and anti-inflammatory cytokines [J].
Reale, M ;
Iarlori, C ;
Gambi, F ;
Feliciani, C ;
Salone, A ;
Toma, L ;
DeLuca, G ;
Salvatore, M ;
Conti, P ;
Gambi, D .
JOURNAL OF NEUROIMMUNOLOGY, 2004, 148 (1-2) :162-171
[28]  
SAWADA M, 1995, J NEUROCHEM, V64, P1973
[29]   Cholinergic modulation of microglial activation by α7 nicotinic receptors [J].
Shytle, RD ;
Mori, T ;
Townsend, K ;
Vendrame, M ;
Sun, N ;
Zeng, J ;
Ehrhart, J ;
Silver, AA ;
Sanberg, PR ;
Tan, J .
JOURNAL OF NEUROCHEMISTRY, 2004, 89 (02) :337-343
[30]   The inflammatory reflex [J].
Tracey, KJ .
NATURE, 2002, 420 (6917) :853-859