Related Experiment Video
Updated: Jun 12, 2025
Assessment of Spontaneous Alternation, Novel Object Recognition and Limb Clasping in Transgenic Mouse Models of Amyloid-β and Tau Neuropathology
Published on: May 28, 2017
Anisomycin alleviates cognitive impairments and pathological features in 3xTg-AD mice
Juan-Juan Jiao1, Yang Hu2, Yu-Jia Cui1
1Department of Physiology Shanxi Medical University, Taiyuan, China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China; Key Laboratory of Cellular Physiology in Shanxi Province, Shanxi Medical University, Taiyuan, China.
Abstract:
Neuroinflammation plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). Anisomycin is a pyrrolidine antibiotic isolated from Streptomyces griseolus, which is an efficient anti-inflammatory agent that functions both in vivo and in vitro. However, it is not clear whether anisomycin can exert neuroprotective effect in AD. In the present study, anisomycin was intragastrically administrated to female triple-transgenic AD (3xTg-AD) model mice, then Morris water maze test was used to observe the long-term spatial memory of mice, the in vivo hippocampal field potential recording was performed to evaluate the synaptic plasticity, the Western blot and immunofluorescence were employed to detect pathological changes, and the bioinformatics analysis was used to predict the potential target of anisomycin exerting effects in AD. The results showed that anisomycin ameliorated the long-term spatial memory deficits, improved LTP depression and increased the expression of PSD-95, reduced the Aβ and tau pathologies, and alleviated the activation of microglia and astrocytes in the brains of 3xTg-AD mice. In addition, the results from bioinformatics analysis showed that the potential target of anisomycin focused on inflammatory pathway. These results indicated that anisomycin exerts neuroprotective effects in 3xTg-AD mice by alleviating neuroinflammation, but the potential mechanism of anisomycin exerting neuroprotective effects needs to be further investigated.
Insights
Anisomycin, an anti-inflammatory antibiotic, improved memory and reduced Alzheimer's disease (AD) pathologies in a mouse model. This suggests potential neuroprotective effects by targeting neuroinflammation in AD.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Neuroinflammation is a key factor in Alzheimer's disease (AD) development.
- Anisomycin is an antibiotic with known anti-inflammatory properties.
- The neuroprotective potential of anisomycin in AD remains unexplored.
Purpose of the Study:
- To investigate the neuroprotective effects of anisomycin in a mouse model of Alzheimer's disease.
- To evaluate anisomycin's impact on cognitive function, synaptic plasticity, and AD-related pathologies.
- To explore the potential molecular targets of anisomycin in the context of AD.
Main Methods:
- Intragastric administration of anisomycin to triple-transgenic AD (3xTg-AD) mice.
- Assessment of long-term spatial memory using the Morris water maze test.
- In vivo hippocampal field potential recording to measure synaptic plasticity (LTP).
- Western blot and immunofluorescence assays to analyze Aβ, tau, and glial activation.
- Bioinformatics analysis to predict anisomycin's molecular targets.
Main Results:
- Anisomycin treatment significantly improved spatial memory deficits in 3xTg-AD mice.
- Synaptic plasticity, indicated by LTP, was enhanced, and PSD-95 expression increased.
- Anisomycin reduced amyloid-beta (Aβ) and tau pathologies.
- Activation of microglia and astrocytes, markers of neuroinflammation, was alleviated.
- Bioinformatics analysis suggested anisomycin's targets are primarily within inflammatory pathways.
Conclusions:
- Anisomycin demonstrates significant neuroprotective effects in a mouse model of Alzheimer's disease.
- These benefits are associated with the amelioration of neuroinflammation, Aβ and tau pathologies, and improved synaptic function.
- Anisomycin's anti-inflammatory action is a likely mechanism for its neuroprotective effects in AD, warranting further investigation.
