Inhibition of LTP by beta-amyloid is prevented by activation of β2 adrenoceptors and stimulation of the cAMP/PKA signalling pathway

被引：60

作者：

Wang, Qin-wen ^{[1
,2
]}

Rowan, Michael J. ^{[3
]}

Anwyl, Roger ^{[1
]}

机构：

[1] Trinity Coll Dublin, Dept Physiol, Dublin 2, Ireland

[2] Ningbo Univ, Dept Physiol & Pharmacol, Sch Med, Ningbo 315211, Zhejiang, Peoples R China

[3] Trinity Coll Dublin, Dept Expt Therapeut, Dublin 2, Ireland

来源：

NEUROBIOLOGY OF AGING | 2009年 / 30卷 / 10期

关键词：

Beta-amyloid; Alzheimer's disease; Noradrenaline; PKA; LTP; Hippocampus; LONG-TERM POTENTIATION; NITRIC-OXIDE SYNTHASE; NOREPINEPHRINE; INFLAMMATION; EXPRESSION; INDUCTION; ALZHEIMER; DISEASE; SYSTEM;

D O I：

10.1016/j.neurobiolaging.2007.12.004

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

Beta-amyloid (A beta) is the main component of the extracellular plaques present in patients with Alzheimer's disease (AD) and studies have shown that exogenous application of A beta results in neurodegeneration. As a model of the neurodegenerative action of A beta, we have previously shown that acutely applied A beta inhibits the induction of LTP in the hippocampus in vitro. In the present studies, we have studied the effect of beta-adrenoceptor activation on the A beta inhibition of LTP. Pharmacological activation of beta 2 adrenoceptors, but not of beta 1 adrenoceptors, was found to prevent the A beta evoked inhibition of LTP in the dentate gyrus of adult animals. The prevention of the effect of A beta was shown to occur via the cAMP/PKA signaling pathway as the adenylate cyclase-stimulating agent forskolin prevented the A beta inhibition of LTP, an action prevented by the PKA inhibitor, Rp-8-Br-cAMPs. We suggest microglia as a likely site of action of the neuroprotective effect of beta 2 adrenoceptor activation. Therapeutic treatment for AD may include agents that activate beta 2 receptors and elevate cAMP. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：1608 / 1613

页数：6

共 33 条

[1] Inflammation and Alzheimer's disease [J].

Akiyama, H ;

Barger, S ;

Barnum, S ;

Bradt, B ;

Bauer, J ;

Cole, GM ;

Cooper, NR ;

Eikelenboom, P ;

Emmerling, M ;

Fiebich, BL ;

Finch, CE ;

Frautschy, S ;

Griffin, WST ;

Hampel, H ;

Hull, M ;

Landreth, G ;

Lue, LF ;

Mrak, R ;

Mackenzie, IR ;

McGeer, PL ;

O'Banion, MK ;

Pachter, J ;

Pasinetti, G ;

Plata-Salaman, C ;

Rogers, J ;

Rydel, R ;

Shen, Y ;

Streit, W ;

Strohmeyer, R ;

Tooyoma, I ;

Van Muiswinkel, FL ;

Veerhuis, R ;

Walker, D ;

Webster, S ;

Wegrzyniak, B ;

Wenk, G ;

Wyss-Coray, T .

NEUROBIOLOGY OF AGING, 2000, 21 (03) :383-421

[2]

Bamberger ME, 2003, J NEUROSCI, V23, P2665

[3]

Bondareff W, 1987, Alzheimer Dis Assoc Disord, V1, P256, DOI 10.1097/00002093-198701040-00005

[4] Inhibition of microglial superoxide anion production by isoproterenol and dexamethasone [J].

Colton, CA ;

Chernyshev, ON .

NEUROCHEMISTRY INTERNATIONAL, 1996, 29 (01) :43-53

[5]

Combs CK, 2001, J NEUROSCI, V21, P1179

[6] Mechanisms of neuronal death in Alzheimer's disease [J].

Cotman, CW ;

Su, JH .

BRAIN PATHOLOGY, 1996, 6 (04) :493-506

[7] Block of LTP in rat hippocampus in vivo by beta-amyloid precursor protein fragments [J].

Cullen, WK ;

Suh, YH ;

Anwyl, R ;

Rowan, MJ .

NEUROREPORT, 1997, 8 (15) :3213-3217

[8] Inhibition of microglial inflammatory responses by norepinephrine: effects on nitric oxide and interleukin-1β production [J].

Dello Russo, Cinzia ;

Boullerne, Anne I. ;

Gavrilyuk, Vitaliy ;

Feinstein, Douglas L. .

JOURNAL OF NEUROINFLAMMATION, 2004, 1 (1)

[9] INFLAMMATORY MECHANISMS IN ALZHEIMERS-DISEASE [J].

EIKELENBOOM, P ;

ZHAN, SS ;

VANGOOL, WA ;

ALLSOP, D .

TRENDS IN PHARMACOLOGICAL SCIENCES, 1994, 15 (12) :447-450

[10]

Feinstein DL, 1998, J NEUROCHEM, V70, P1484

← 1 2 3 4 →