Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging

被引：96

作者：

Albayram, Onder ^{[1
]}

Alferink, Judith ^{[1
,2
]}

Pitsch, Julika ^{[3
]}

Piyanova, Anastasia ^{[1
]}

Neitzert, Kim ^{[1
]}

Poppensieker, Karola ^{[1
]}

Mauer, Daniela ^{[1
]}

Michel, Kerstin ^{[1
]}

Legler, Anne ^{[4
]}

Becker, Albert ^{[3
]}

Monory, Krisztina ^{[4
]}

Lutz, Beat ^{[4
]}

Zimmer, Andreas ^{[1
]}

Bilkei-Gorzo, Andras ^{[1
]}

机构：

[1] Univ Bonn, Inst Mol Psychiat, D-53127 Bonn, Germany

[2] Univ Bonn, Dept Psychiat & Psychotherapy, D-53127 Bonn, Germany

[3] Univ Bonn, Inst Neuropathol, D-53127 Bonn, Germany

[4] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Physiol Chem, D-55128 Mainz, Germany

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 27期

关键词：

glial regulation; Morris water maze; stereological quantification; CD40; expression; telemetric EEG recording; ENDOCANNABINOID SYSTEM; MICROGLIAL CELLS; OXIDATIVE STRESS; GENE-EXPRESSION; ACTIVATION; AGE; MEMORY; INTERLEUKIN-6; NEUROGENESIS; HIPPOCAMPUS;

D O I：

10.1073/pnas.1016442108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Brain aging is associated with cognitive decline that is accompanied by progressive neuroinflammatory changes. The endocannabinoid system (ECS) is involved in the regulation of glial activity and influences the progression of age-related learning and memory deficits. Mice lacking the Cnr1 gene (Cnr1(-/-)), which encodes the cannabinoid receptor 1 (CB1), showed an accelerated age-dependent deficit in spatial learning accompanied by a loss of principal neurons in the hippocampus. The age-dependent decrease in neuronal numbers in Cnr1(-/-) mice was not related to decreased neurogenesis or to epileptic seizures. However, enhanced neuroinflammation characterized by an increased density of astrocytes and activated microglia as well as an enhanced expression of the inflammatory cytokine IL-6 during aging was present in the hippocampus of Cnr1(-/-) mice. The ongoing process of pyramidal cell degeneration and neuroinflammation can exacerbate each other and both contribute to the cognitive deficits. Deletion of CB1 receptors from the forebrain GABAergic, but not from the glutamatergic neurons, led to a similar neuronal loss and increased neuroinflammation in the hippocampus as observed in animals lacking CB1 receptors in all cells. Our results suggest that CB1 receptor activity on hippocampal GABAergic neurons protects against age-dependent cognitive decline by reducing pyramidal cell degeneration and neuroinflammation.

引用

页码：11256 / 11261

页数：6

共 54 条

[51] Aging-dependent changes of microglial cells and their relevance for neurodegenerative disorders [J].

von Bernhardi, Rommy ;

Tichauer, Juan E. ;

Eugenin, Jaime .

JOURNAL OF NEUROCHEMISTRY, 2010, 112 (05) :1099-1114

[52] ATP induces a rapid and pronounced increase in 2-arachidonoylglycerol production by astrocytes, a response limited by monoacylglycerol lipase [J].

Walter, L ;

Dinh, T ;

Stella, N .

JOURNAL OF NEUROSCIENCE, 2004, 24 (37) :8068-8074

[53] Nonpsychotropic cannabinoid receptors regulate microglial cell migration [J].

Walter, L ;

Franklin, A ;

Witting, A ;

Wade, C ;

Xie, YH ;

Kunos, G ;

Mackie, K ;

Stella, N .

JOURNAL OF NEUROSCIENCE, 2003, 23 (04) :1398-1405

[54] Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice [J].

Zimmer, A ;

Zimmer, AM ;

Hohmann, AG ;

Herkenham, M ;

Bonner, TI .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (10) :5780-5785

← 1 2 3 4 5 6 →