Age Inﬂuences Microglial Activation After Cuprizone-Induced Demyelination

Front. Aging Neurosci., 2018 · DOI: 10.3389/fnagi.2018.00278 · Published: September 20, 2018

Simple Explanation

This study investigates how microglia, the immune cells of the brain, respond to demyelination differently in young versus middle-aged mice. The researchers used a cuprizone model to induce demyelination and then analyzed various microglial markers in the hippocampus and corpus callosum. The results showed that age-related changes in microglia exist and that their response to demyelination varies depending on the brain region and the age of the animal.

Study Duration

8 weeks

Participants

48 male C57BL/6J mice, young (2-month-old) and middle-aged (10-month-old)

Evidence Level

Not specified

Key Findings

1
Age-related microglial changes in healthy controls were more pronounced in the gray matter region, with higher levels of F4/80 and Marco and lower expression of CD68 in middle-aged mice.
2
During de- and remyelination, a stronger increase of the microglial markers Iba-1, CD68 and TSPO was observed in the splenium of the younger groups.
3
The induction of the anti-inﬂammatory markers CD206 and CD163 was stronger in the middle-aged group, but also differed between the two analyzed regions.

Research Summary

The study investigated the impact of age on microglial responses to demyelination using the cuprizone model in young and middle-aged mice, focusing on the hippocampus and corpus callosum. Results showed that age-related microglial changes exist and that their response to demyelination varies depending on the brain region and age. The findings suggest that anti-inflammatory characteristics are more pronounced in middle-aged mice during remyelination, and activation of microglia in the young CNS seems to be stronger and longer lasting.

Practical Implications

Understanding Age-Related MS Progression

The study sheds light on how aging influences microglial responses in demyelinating conditions like MS, potentially explaining why regeneration fails more often in older individuals.

Region-Specific Targeting

The findings highlight the importance of considering region-specific differences when developing therapies targeting microglia in demyelinating diseases.

Personalized Treatment Strategies

The results suggest that treatment strategies for demyelinating diseases might need to be tailored to the age of the patient to optimize microglial responses and promote myelin repair.

Study Limitations

1
The study only examines microglial alterations after a relatively acute demyelination period.
2
The study only analyzed male mice.
3
It would be interesting to do functional studies with M2-polarized microglia/macrophages from aged mice after cuprizone-induced demyelination to find out whether they are indeed beneficial for myelin repair.

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