Early onset of aging-like changes is restricted to cognitive abilities and skin structure in Cnr1-/- mice

被引:46
作者
Bilkei-Gorzo, Andras [1 ]
Drews, Eva [1 ]
Albayram, Oender [1 ]
Piyanova, Anastasia [1 ]
Gaffal, Evelyn [2 ]
Tueting, Thomas [2 ]
Michel, Kerstin [1 ]
Mauer, Daniela [1 ]
Maier, Wolfgang [3 ]
Zimmer, Andreas [1 ]
机构
[1] Univ Bonn, Inst Mol Psychiat, D-53127 Bonn, Germany
[2] Univ Bonn, Clin Dermatol & Allergol, D-53127 Bonn, Germany
[3] Univ Bonn, Dept Psychiat & Psychotherapy, D-53127 Bonn, Germany
关键词
Cannabinoid; 1; receptor; Skin aging; Testis; Hearing loss; Locomotor activity; Knockout mouse model; Learning and memory; CB1 CANNABINOID RECEPTOR; MESSENGER-RNA LEVELS; OXIDATIVE STRESS; ENDOCANNABINOID SYSTEM; SELECTIVE VULNERABILITY; HIPPOCAMPAL-NEURONS; ENERGY-METABOLISM; DOWN-REGULATION; SPATIAL MEMORY; KNOCKOUT MICE;
D O I
10.1016/j.neurobiolaging.2010.07.009
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
Genetic deletion of the cannabinoid 1 (CB1) receptor leads to an early onset of learning and memory impairment. In the present study we asked whether the lack of CB1 receptors accelerates aging in general or is selective for cognitive functions. We therefore compared the onset and dynamics of age-dependent changes in social memory, locomotor activity, hearing ability, and in the histopathology of peripheral organs between wild-type and Cnr1 knockout (Cnr1(-/-)) mice. We observed deficits in social memory already in 3-month-old Cnr1(-/-) mice. In contrast, wild-type animals showed such deficits at the age of 6 months. Sensory and motor functions were similar between the genotypes. Thus, hearing loss for higher frequencies and the development of hypomotility showed a similar age-dependent course. In the periphery we detected an early onset of aging-like histological changes in the skin, but not in other organs. We conclude that the lack of CB1 receptor does not induce accelerated aging in general, but induces changes in cognitive function and in skin structure that resemble those associated with aging. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:200.e11 / 200.e22
页数:12
相关论文
共 95 条
[1]   Regulation of neuronal and glial proteins by leptin:: Implications for brain development [J].
Ahima, RS ;
Bjorbæk, C ;
Osei, S ;
Flier, JS .
ENDOCRINOLOGY, 1999, 140 (06) :2755-2762
[2]   Emergence of a powerful connection between sensory and cognitive functions across the adult life span: A new window to the study of cognitive aging? [J].
Baltes, PB ;
Lindenberger, U .
PSYCHOLOGY AND AGING, 1997, 12 (01) :12-21
[3]   DOES IMPAIRMENT OF ENERGY-METABOLISM RESULT IN EXCITOTOXIC NEURONAL DEATH IN NEURODEGENERATIVE ILLNESSES [J].
BEAL, MF .
ANNALS OF NEUROLOGY, 1992, 31 (02) :119-130
[4]   Changes in cannabinoid receptor binding and mRNA levels in several brain regions of aged rats [J].
Berrendero, F ;
Romero, J ;
García-Gil, L ;
Suarez, I ;
De la Cruz, P ;
Ramos, JA ;
Fernández-Ruiz, JJ .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 1998, 1407 (03) :205-214
[5]   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
[6]   Behavioral phenotype of pre-proenkephalin-deficient mice on diverse congenic backgrounds [J].
Bilkei-Gorzo, A ;
Racz, I ;
Michel, K ;
Zimmer, A ;
Klingmüller, D ;
Zimmer, A .
PSYCHOPHARMACOLOGY, 2004, 176 (3-4) :343-352
[7]   Neural mechanisms of ageing and cognitive decline [J].
Bishop, Nicholas A. ;
Lu, Tao ;
Yankner, Bruce A. .
NATURE, 2010, 464 (7288) :529-535
[8]   Expression of type-1 cannabinoid receptor during rat postnatal testicular development: Possible involvement in adult Leydig cell differentiation [J].
Cacciola, Giovanna ;
Chioccarelli, Teresa ;
Mackie, Ken ;
Meccariello, Rosaria ;
Ledent, Catherine ;
Fasano, Silvia ;
Pierantoni, Riccardo ;
Cobellis, Gilda .
BIOLOGY OF REPRODUCTION, 2008, 79 (04) :758-765
[9]  
CERVOSNAVARRO J, 1991, CRIT REV NEUROBIOL, V6, P149
[10]   Lifelong running reduces oxidative stress and degenerative changes in the testes of mice [J].
Chigurupati, Srinivasulu ;
Son, Tae Gen ;
Hyun, Dong-Hoon ;
Lathia, Justin D. ;
Mughal, Mohamed R. ;
Savell, Jason ;
Li, Shuan C. ;
Nagaraju, G. P. C. ;
Chan, Sic L. ;
Arumugam, Thiruma V. ;
Mattson, Mark P. .
JOURNAL OF ENDOCRINOLOGY, 2008, 199 (02) :333-341