Inflammatory reactions can change the brain's immune cells in the long term - meaning that these cells have an 'immunological memory'. This memory may influence the progression of neurological disorders that occur later in life, and is therefore a previously unknown factor that could influence the severity of these diseases according to scientists in the journal Nature.
Microglia are immune cells that only occur in the brain. They protect the brain by cleansing it of intruders and toxic substances. However, in certain situations they can also cause damage. Therefore, they have long been suspected of playing a central role in neurodegenerative diseases.
As microglia are very long-lived, the scientists were keen to find out whether environmental factors change these immune cells over time and what effect this can have on brain health. "Epidemiological studies have shown that infectious diseases and inflammation suffered during a life-time can affect the severity of Alzheimer's disease much later in life. We therefore asked ourselves whether an immunological memory in these long-lived microglia could be communicating this risk," explains the study lead.
In order to address this question, researchers triggered in-flammation in mice, outside their brains; it was already known that such an inflammation can stimulate an immune reaction in the brain. However, it was not clear whether microglia might be able to remember a previous inflammation. As it turned out: Depending on how often the scientists repeated this process, they were able to induce two different states in the microglia: "training" and "tolerance". The first inflammatory stimulus trained the microglia, causing them to react more strongly to the second. However, after a fourth stimulus, tolerance had occurred and the microglia barely responded.
Next, the researchers investigated how microglia training and tolerance affected the formation of amyloid plaques in the long term. Such "plaques" are characteristic toxic deposits that accumulate in the brains of patients with Alzheimer's disease. In a mouse model of Alzheimer's pathology, the scientists observed that trained microglia amplified the formation of plaques even months after their immunological memory had been triggered, thus causing the disease to become more severe. In contrast, tolerant microglia reduced plaque load. The scientists also noticed similar effects in a mouse model of stroke.
In order to understand these effects more precisely, researchers investigated epigenetic changes in the microglia, i.e. chemical modifications to the DNA or its packaging proteins that cause certain genes to become more or less active. As epigenetic modifications are very stable, the researchers saw in them a possible cause for the long-term behavioral changes exhibited by the microglia. This hypothesis turned out to be correct: even many months after the initial immune stimulus, both the trained and the tolerant microglia showed specific epigenetic changes and corresponding differences in gene activation. This molecular reprogramming changed important functions in the microglia, such as their ability to remove amyloid plaques. And this affected Alzheimer's pathology.
"It is possible that also in humans, inflammatory diseases that primarily develop outside the brain could trigger epigenetic reprogramming inside the brain," says the author. Both infections and diseases such as diabetes or arthritis are associated with inflammatory reactions and are known risk factors for Alzheimer's disease. The brain's immunological memory - epigenetically modified microglia - is one possible explanation for this effect. Therefore, researchers are now investigating the conditions under which microglia undergo epigenetic changes in humans and looking at the therapeutic possibilities that may arise from this.
https://www.dzne.de/en/news/public-relations/press-releases/press/an-immunological-memory-in-the-brain/
https://www.nature.com/articles/s41586-018-0023-4
Latest News
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Molecular causes of differe…
By newseditor
Posted 16 Apr
Cell's 'garbage disposal' h…
By newseditor
Posted 16 Apr
Other Top Stories
A redox-dependent skin pigmentation mechanism identified!
Read more
Brain damage causes microtubule disruption and mitotic activity sim…
Read more
Controlling the pruning and strengthening of neuron branches
Read more
Molecular motor in regulating memory
Read more
Adhesion proteins mediate inhibitory synapse specificity in the cortex
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Oligodendroglial macroautop…
By newseditor
Posted 17 Apr
COPII with ALG2 and ESCRTs…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar