Enhanced microglial activity in FAAH-/- animals

被引:12
作者
Ativie, F. [1 ]
Albayram, O. [1 ]
Bach, K. [1 ]
Pradier, B. [1 ]
Zimmer, A. [1 ]
Bilkei-Gorzo, A. [1 ]
机构
[1] Univ Bonn, Inst Mol Psychiat, Bonn, Germany
关键词
Neuroinflammation; Anandamide; FAAH; Microglia; Astrocyte; Ageing; FATTY-ACID AMIDE; TRAUMATIC BRAIN-INJURY; CANNABINOID RECEPTORS; HYDROLASE FAAH; CB2; RECEPTORS; TNF-ALPHA; ANANDAMIDE; INFLAMMATION; CELLS; MICE;
D O I
10.1016/j.lfs.2014.12.016
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
Aims: Several lines of evidence suggest that the endocannabinoid system is involved in the regulation of glial activity. Enhanced levels of the endocannabinoid N-arachidonoyl ethanolamine (AEA, also referred to as anandamide) as well as non-cannabinoid lipids like palmitoylethanolamine (PEA) due to genetic deletion or pharmacologic blockade of its degrading enzyme fatty acid amide hydrolase (FAAH) reduced neuroinflammatoiy changes in models of neurodegeneration. Now we addressed the question if genetic deletion of FAAH also influences agerelated neuroinflammation. Main methods: To answer this question we compared the number and size of microglia in young and old wild-type and FAAH(-/-) mice and analysed the distribution of microglia sizes in the four groups. Additionally, we analysed IL-6 and IL-1 beta levels with ELISA and astrocyte activities as ratio of GFAP-positive areas in the hippocampus. Key findings: Ageing was associated with an increased number and activity of microglia, elevated IL-6 and IL-1 beta levels and enhanced area covered by astrocytes in wild-type animals. Unexpectedly, in FAAH(-/-) animals the number of microglia and the ratio of activated microglia and IL-1 beta level were already higher in young animals than in age-matched wild-type controls. There was no further age-related increase in these inflammation markers in the knockout line. Significance: Our results suggest that AEA is involved in the regulation of microglia activity. Life-long elevation of AEA levels disturbs microglial regulation and leads to pro-inflammatory changes. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:52 / 56
页数:5
相关论文
共 54 条
[1]   Interleukins, from 1 to 37, and interferon-γ: Receptors, functions, and roles in diseases [J].
Akdis, Muebeccel ;
Burgler, Simone ;
Crameri, Reto ;
Eiwegger, Thomas ;
Fujita, Hiroyuki ;
Gomez, Enrique ;
Klunker, Sven ;
Meyer, Norbert ;
O'Mahony, Liam ;
Palomares, Oscar ;
Rhyner, Claudio ;
Quaked, Nadia ;
Schaffartzik, Anna ;
Van De Veen, Willem ;
Zeller, Sabine ;
Zimmermann, Maya ;
Akdis, Cezmi A. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2011, 127 (03) :701-U317
[2]   Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging [J].
Albayram, Onder ;
Alferink, Judith ;
Pitsch, Julika ;
Piyanova, Anastasia ;
Neitzert, Kim ;
Poppensieker, Karola ;
Mauer, Daniela ;
Michel, Kerstin ;
Legler, Anne ;
Becker, Albert ;
Monory, Krisztina ;
Lutz, Beat ;
Zimmer, Andreas ;
Bilkei-Gorzo, Andras .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (27) :11256-11261
[3]   Harnessing the anti-inflammatory potential of palmitoylethanolamide [J].
Alhouayek, Mireille ;
Muccioli, Giulio G. .
DRUG DISCOVERY TODAY, 2014, 19 (10) :1632-1639
[4]   Decreased age-related cardiac dysfunction, myocardial nitrative stress, inflammatory gene expression, and apoptosis in mice lacking fatty acid amide hydrolase [J].
Batkai, Sandor ;
Rajesh, Mohanraj ;
Mukhopadhyay, Partha ;
Hasko, Gyorgy ;
Liaudet, Lucas ;
Cravatt, Benjamin F. ;
Csiszar, Anna ;
Ungvari, Zoltan ;
Pacher, Pal .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2007, 293 (02) :H909-H918
[5]   β-Amyloid exacerbates inflammation in astrocytes lacking fatty acid amide hydrolase through a mechanism involving PPAR-α, PPAR-γ and TRPV1, but not CB1 or CB2 receptors [J].
Benito, Cristina ;
Maria Tolon, Rosa ;
Isabel Castillo, Ana ;
Ruiz-Valdepenas, Lourdes ;
Antonio Martinez-Orgado, Jose ;
Javier Fernandez-Sanchez, Francisco ;
Vazquez, Carmen ;
Cravatt, Benjamin F. ;
Romero, Julian .
BRITISH JOURNAL OF PHARMACOLOGY, 2012, 166 (04) :1474-1489
[6]   Early age-related cognitive impairment in mice lacking cannabinoid CB1 receptors [J].
Bilkei-Gorzo, A ;
Racz, I ;
Valverde, O ;
Otto, M ;
Michel, K ;
Sarstre, M ;
Zimmer, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (43) :15670-15675
[7]   Early onset of aging-like changes is restricted to cognitive abilities and skin structure in Cnr1-/- mice [J].
Bilkei-Gorzo, Andras ;
Drews, Eva ;
Albayram, Oender ;
Piyanova, Anastasia ;
Gaffal, Evelyn ;
Tueting, Thomas ;
Michel, Kerstin ;
Mauer, Daniela ;
Maier, Wolfgang ;
Zimmer, Andreas .
NEUROBIOLOGY OF AGING, 2012, 33 (01) :200.e11-200.e22
[8]   Cannabinoid Receptors and Endocannabinoids: Role in Neuroinflammatory and Neurodegenerative Disorders [J].
Bisogno, Tiziana ;
Di Marzo, Vincenzo .
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS, 2010, 9 (05) :564-573
[9]   Antinociceptive activity of the endogenous fatty acid amide, palmitylethanolamide [J].
Calignano, A ;
La Rana, G ;
Piomelli, D .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2001, 419 (2-3) :191-198
[10]   Antiinflammatory action of endocannabinoid palmitoylethanolamide and the synthetic cannabinoid nabilone in a model of acute inflammation in the rat [J].
Conti, S ;
Costa, B ;
Colleoni, M ;
Parolaro, D ;
Giagnoni, G .
BRITISH JOURNAL OF PHARMACOLOGY, 2002, 135 (01) :181-187