Causative factor to cerebral inflammation in a transgenic mouse model of Alzheimer's disease
10.3760/cma.j.issn.1008-6315.2011.02.001
- VernacularTitle:转基因阿尔茨海默病小鼠脑内炎症反应的诱发因素研究
- Author:
Ni MAO
;
Liu LIU
;
Jian HAO
;
Rui LIU
;
Gesheng LEI
;
Wei ZHANG
;
Jianting MIAO
- Publication Type:Journal Article
- Keywords:
Alzheimer's disease;
Transgenic mice;
Inflammatory factor;
Amyloid plaque
- From:
Clinical Medicine of China
2011;27(2):113-116
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the changes of cerebral inflammation-related markers in brain of a transgenic mouse model of Alzheimer's disease (AD) ,and to determine the causative factor to the development of cerebral inflammation in AD. Methods 3- and 12-month-old β-amyloid protein precursor ( APP)/presenilin (PSI) transgenic mice and age-matched wild-type mice (WT) were used in the study. The changes of amyloid plaques, inflammatory factors ( interleukin 1β ( IL-1β ); interleukin 6( IL-6 ); tumor necrosis factor α (TNFα) ;prostaglandin E2 (PGE2)) in the brains among these mice were measured by immunohistochemistry and ELISA. Results Immunohistochemical analysis revealed that no amyloid plaques and activated astrocytes as well as microglia were observed in the 3-month-old APP/PS1 mice. There were no significant differences in the levels of inflammatory factors (IL-1β, IL-6 ,TNFα,and PGE2) between the 3-month-old APP/PS1 and WT mice ( Ps ＞ 0. 05 ). However, abundant amyloid plaques accompanied by a remarkable increase of activated astrocytes and microglia were found in the brain of the 12-month-old APP/PS1 mice. The levels of inflammatory factors (IL-1β,IL-6,TNFα, and PGE2 ) were significantly increased in the 12-month-old APP/PS1 mice ([56. 02 ±9. 04] ng/g, [8. 66 ±0.83] ng/g, [97.48 ±26.58] ng/g, [72. 18 ±21.01] ng/g) than in the WT mice ([29. 18 ± 6. 03] ng/g, [7. 73 ± 0. 74] ng/g, [61.98 ±11.11] ng/g, [37. 23 ± 10. 96] ng/g) and the 3-month-old APP/PS1 mice ( [30. 05 ± 3.53] ng/g, [7.43 ± 1.17] ng/g, [59.34 ± 10. 07] ng/g, [42. 56 ±5.93] ng/g) (P＜0.05,or P＜0.01,respectively). Conclusion This study demonstrates that the APP/PS1mice did not show cerebral inflammation before the appearance of amyloid plaques, and exhibited remarkable inflammation after amyloid plaque deposition. These findings suggest that the induction of cerebral inflammation is tightly associated with amyloid plaque formation, and deposition of amyloid-beta protein (Aβ) may be the direct causative factor to the development of cerebral inflammation in AD.
