Related Experiment Video
Updated: Jan 20, 2026
Intracerebroventricular Injection of Amyloid-β Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits
Published on: March 16, 2016
MicroRNA-181a protects against pericyte apoptosis via directly targeting FOXO1: implication for ameliorated cognitive
Qingbin Wu1, Xiaochen Yuan1, Jing Bai2
1Key Laboratory for Microcirculation, Ministry of Health, Institute of Microcirculation, Chinese Academy Medical Sciences and Pecking Union Medical College, Beijing, China.
Abstract:
MicroRNAs (miRNAs) have emerged as critical regulators in the pathology of Alzheimer's disease (AD). MiR-181a is associated with hippocampal memory formation and aberrantly expressed in patients with mild cognitive impairment (MCI), however, little is known about its role and underlying mechanism involved in AD. Here, we report that miR-181a expression declines in APP/PS1 mice, synchronous with the increase in amyloid β (Aβ) level, which suggests a reverse correlation between miR-181a level and AD development. Additionally, lentiviral overexpression of miR-181a via intrahippocampal injection ameliorates cognitive deficits and amyloid plaque deposition in APP/PS1 mice, indicating a beneficial role of miR-181a against AD progression. Moreover, miR-181a decelerates pericyte loss and blood-brain barrier breakdown in APP/PS1 mice. Furthermore, miR-181a protects against Aβ accumulation-induced pericyte apoptosis in vitro, which is attributed to the negative regulation of FOXO1 by miR-181a, since FOXO1 restoration abolishes miR-181a protective role against pericyte apoptosis. Altogether, these results may identify miR-181a as a novel regulator of AD pathology, and also implicate that the protection of miR-181a in blood-brain barrier pericytes may underlie its ameliorating effect on APP/PS1 mice.
Insights
MicroRNA-181a (miR-181a) levels decrease in Alzheimer's disease (AD) models. Restoring miR-181a improves cognition and reduces amyloid plaques by protecting brain pericytes.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are key regulators in Alzheimer's disease (AD) pathology.
- MiR-181a influences memory and is altered in mild cognitive impairment (MCI).
- The specific role of miR-181a in AD pathogenesis remains unclear.
Purpose of the Study:
- To investigate the role and mechanism of miR-181a in Alzheimer's disease.
- To determine the effect of miR-181a on cognitive function and neuropathology in AD mouse models.
- To explore miR-181a's impact on blood-brain barrier integrity and pericytes.
Main Methods:
- Assessed miR-181a expression in APP/PS1 mice and correlated it with amyloid-beta (Aβ) levels.
- Overexpressed miR-181a in APP/PS1 mice using lentiviral vectors via intrahippocampal injection.
- Evaluated cognitive function, amyloid plaque load, pericyte loss, and blood-brain barrier integrity.
- Investigated miR-181a's effect on Aβ-induced pericyte apoptosis in vitro and its regulation of FOXO1.
Main Results:
- miR-181a expression decreased in APP/PS1 mice as Aβ levels increased.
- miR-181a overexpression ameliorated cognitive deficits and reduced amyloid deposition in APP/PS1 mice.
- miR-181a protected against pericyte loss and blood-brain barrier breakdown, and inhibited Aβ-induced pericyte apoptosis by downregulating FOXO1.
Conclusions:
- miR-181a acts as a protective factor against Alzheimer's disease progression.
- The beneficial effects of miR-181a involve the protection of blood-brain barrier pericytes via FOXO1 regulation.
- miR-181a represents a potential therapeutic target for Alzheimer's disease.
Related Concept Videos
08:01Intracerebroventricular Injection of Amyloid-β Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits
07:42Dual-Task Stroop Paradigm for Detecting Cognitive Deficits in High-Functioning Stroke Patients
06:11Nest Building Behavior as an Early Indicator of Behavioral Deficits in Mice
05:48The Adventures of Fundi Intervention Based on the Cognitive and Emotional Processing in Attention Deficit Hyperactive Disorder Patients
09:45An In Vitro Protocol for Evaluating MicroRNA Levels, Functions, and Associated Target Genes in Tumor Cells
07:02In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice