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Inhibition of microRNA-155 Alleviates Cognitive Impairment in Alzheimer’s Disease and Involvement of Neuroinflammation

[ Vol. 16 , Issue. 6 ]

Author(s):

Dandan Liu, Dandan Zhao, Yingkai Zhao, Yan Wang, Yong Zhao* and Chengfei Wen*   Pages 473 - 482 ( 10 )

Abstract:


Background: Neuroinflammation has important effects on cognitive functions in the pathophysiological process of Alzheimer’s Disease (AD). In the current report, we determined the effects of microRNA-155 (miR-155) on the levels of IL-1β, IL-6 and TNF-α, and their respective receptors in the hippocampus using a rat model of AD.

Methods: Real-time RT-PCR, ELISA and western blot analysis were used to examine the miR-155, PICs and PIC receptors. The Morris water maze and spatial working memory tests were used to assess cognitive functions.

Results: miR-155 was increased in the hippocampus of AD rats, accompanied by amplification of IL-1β, IL-6 and TNF-α. Intracerebroventricular infusion of miR-155 inhibitor, but not its scramble attenuated the increases of IL-1β, IL-6 and TNF-α and upregulation of their receptors. MiR-155 inhibitor also attenuated upregulation of apoptotic Caspase-3 in the hippocampus of AD rats. Notably, inhibition of miR- 155 or PIC receptors largely recovered the impaired learning performance in AD rat.

Conclusion: We showed the critical role of miR-155 in regulating the memory impairment in AD rats likely via engagement of neuroinflammatory mechanisms, suggesting that miR-155 and its signaling molecules may present prospects in preventing and/or improving the development of the impaired cognitive functions in AD.

Keywords:

miroRNA-155, pro-inflammatory cytokines, Caspase-3, hippocampus, Alzheimer's disease, neuroinflammation.

Affiliation:

Center of Physical Examination, The First Hospital of Jilin University Changchun, Jilin 130021, Department of Pediatric Gastroenterology, The First Hospital of Jilin University Changchun, Jilin 130021, Department of Gerontology, The First Hospital of Jilin University Changchun, Jilin 130021, Department of Gerontology, The First Hospital of Jilin University Changchun, Jilin 130021, Department of Thoracic Surgery The First Hospital of Jilin University Changchun, Jilin 130021, Department of Cardiology, The First Hospital (Eastern Division) of Jilin University, Changchun, Jilin 130031



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