Restraining tumor necrosis factor-alpha by thalidomide prevents the Amyloid beta-induced impairment of recognition memory in mice

被引：80

作者：

Alkam, Tursun ^{[2
,3
,7
]}

Nitta, Atsumi ^{[2
,3
]}

Mizoguchi, Hiroyuki ^{[2
,3
,8
]}

Saito, Kuniaki ^{[4
,5
]}

Seshima, Mitsuru ^{[6
]}

Itoh, Akio ^{[2
,3
]}

Yamada, Kiyofumi ^{[2
,3
]}

Nabeshima, Toshitaka ^{[1
,2
,3
,9
]}

机构：

[1] Meijo Univ, Grad Sch Pharmaceut Sci, Dept Chem Pharmacol, Nagoya, Aichi 4688503, Japan

[2] Nagoya Univ, Grad Sch Med, Dept Neuropsychophatmacol, Nagoya, Aichi 4668560, Japan

[3] Nagoya Univ, Grad Sch Med, Hosp Phar,, Nagoya, Aichi 4668560, Japan

[4] Kyoto Univ, Grad Sch Med, Kyoto 6068507, Japan

[5] Kyoto Univ, Fac Med, Kyoto 6068507, Japan

[6] Gifu Univ, Grad Sch Med, Dept Informat Clin Med, Gifu 5011194, Japan

[7] Coll Tradit Uighur Med, Dept Basic Med, Hotan 848000, Peoples R China

[8] Nagoya Univ, Environm Med Res Inst, Futurist Environm Simulat Ctr, Nagoya, Aichi 4648601, Japan

[9] Japanese Drg Org Appropriate Use & Res, Nagoya, Aichi 4680069, Japan

来源：

BEHAVIOURAL BRAIN RESEARCH | 2008年 / 189卷 / 01期

基金：

日本学术振兴会;

关键词：

amyloid beta (A beta(25-35)); tumor necrosis factor-alpha; protein nitration; recognition memory; thalidomide;

D O I：

10.1016/j.bbr.2007.12.014

中图分类号：

B84 [心理学]; C [社会科学总论]; Q98 [人类学];

学科分类号：

03 ; 0303 ; 030303 ; 04 ; 0402 ;

摘要：

No effective remedy has currently been realized to prevent the cognitive impairments of Alzheimer's disease (AD). The interruption of the toxic pathways of amyloid beta peptide (A beta) still remains promising for the treatment. The involvement of tumor necrosis factor-alpha (TNF-alpha) in the toxicity of A beta(1-40) in recent reports provide a fresh target for the interruption. In the current study, we evaluated the feasibility of a strategy that target TNF-alpha to prevent the impairment of memory induced by A beta. The i.c.v-injection of A beta(25-35) increased the hippocampal mRNA expression of both TNF-a and inducible nitric oxide synthase (iNOS), of which the former was stronger. The knock-out of TNF-alpha (TNF-alpha (-/-)) in mouse prevented the increase of iNOS mRNA induced by A beta(25-35). Not only the inhibition of iNOS activity but also TNF-alpha (-/-) prevented the nitration of proteins in the hippocampus and the impairment of recognition memory in mice induced by A beta(25-35). Daily treatment with thalidomide (20 mg/kg), a preferential degrader of TNF-alpha mRNA, or i.c. v.-injection of an anti-TNF-alpha antibody (10 eta g/mouse) prevented the nitration of proteins in the hippocampus and the impairment of recognition memory induced by A beta(25-35) or A beta(1-40) in mice. These results suggested the practicability of targeting TNF-alpha as a preventive strategy against A beta-mediated cognitive impairments. (c) 2007 Elsevier B.V. All rights reserved.

引用

页码：100 / 106

页数：7

共 69 条

[1] β-amyloid stimulation of inducible nitric-oxide synthase in astrocytes is interleukin-1β- and tumor necrosis factor-α (TNFα)-dependent, and involves a TNFα receptor-associated factor- and NFκB-inducing kinase-dependent signaling mechanism [J].

Akama, KT ;

Van Eldik, LJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (11) :7918-7924

[2] Amyloid β-peptide stimulates nitric oxide production in astrocytes through an NFκB-dependent mechanism [J].

Akama, KT ;

Albanese, C ;

Pestell, RG ;

Van Eldik, LJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (10) :5795-5800

[3] A natural scavenger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced by Aβ25-35 [J].

Alkam, Tursun ;

Nitta, Atsumi ;

Mizoguchi, Hiroyuki ;

Itoh, Akio ;

Nabeshima, Toshitaka .

BEHAVIOURAL BRAIN RESEARCH, 2007, 180 (02) :139-145

[4]

Baugh J A, 2001, Curr Opin Drug Discov Devel, V4, P635

[5]

BECKMAN JS, 1994, ANN NY ACAD SCI, V738, P69

[6] PATHOLOGICAL IMPLICATIONS OF NITRIC-OXIDE, SUPEROXIDE AND PEROXYNITRITE FORMATION [J].

BECKMAN, JS ;

CROW, JP .

BIOCHEMICAL SOCIETY TRANSACTIONS, 1993, 21 (02) :330-334

[7] Antioxidant neuroprotection in Alzheimer's disease as preventive and therapeutic approach [J].

Behl, C ;

Moosmann, B .

FREE RADICAL BIOLOGY AND MEDICINE, 2002, 33 (02) :182-191

[8] A high plasma concentration of TNF-α is associated with dementia in centenarians [J].

Bruunsgaard, H ;

Andersen-Ranberg, K ;

Jeune, B ;

Pedersen, AN ;

Skinhoj, P ;

Pedersen, BK .

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, 1999, 54 (07) :M357-M364

[9] Evidence of oxidative damage in Alzheimer's disease brain:: central role for amyloid β-peptide [J].

Butterfield, DA ;

Drake, J ;

Pocernich, C ;

Castegna, A .

TRENDS IN MOLECULAR MEDICINE, 2001, 7 (12) :548-554

[10] Proteomic identification of nitrated proteins in Alzheimer's disease brain [J].

Castegna, A ;

Thongboonkerd, V ;

Klein, JB ;

Lynn, B ;

Markesbery, WR ;

Butterfield, DA .

JOURNAL OF NEUROCHEMISTRY, 2003, 85 (06) :1394-1401

← 1 2 3 4 5 6 7 →