Introducing the brain: microglia functions (Introduction)

by David Turell , Sunday, July 28, 2024, 18:34 (116 days ago) @ David Turell

A new study:

https://www.sciencedaily.com/releases/2024/07/240726113357.htm

"The brain contains many cell types, from the prominent neurons to the lesser-known microglia. The latter are integral to the brain's immune system and play a crucial role as the brain's cleanup crew. A recent study highlights that microglia establish connections with neurons through tunneling nanotubes. The researchers observed that microglia utilize these tubes to facilitate the clearance of toxic proteins from neurons and to promote neuronal health.

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"'We knew that microglia play a role in clearing these protein aggregates but we only learned recently that they can form tunnelling nanotubes, long extensions that can connect distant cells in the brain," explains Prof. Michael Heneka, director of the LCSB, head of the Neuroinflammation group and lead author of the article. "With this study, we wanted to better understand the transfer of cargo between neurons and microglia via these nanotubes and explore the consequences of this exchange for cellular health."

"The researchers employed cultures of neurons and microglia, derived from either mouse models or human stem cells, and used cutting-edge imaging technology to demonstrate that microglia establish contact with neurons through tunnelling nanotubes (TNTs) to alleviate them from toxic protein accumulations. Additionally, the microglia transfer healthy mitochondria, the powerhouses of the cells, to affected neurons, which significantly reduces oxidative stress, restores vital functions and ultimately rescues these nerve cells.

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"In co-cultures of neurons and microglia, the team further observed that when toxic proteins accumulate within neurons, the number of TNTs connecting the two cell types increased and that these nanotubes contained alpha-synuclein and tau particles. The pathological proteins were transferred from neurons to microglia, not vice versa, where they were degraded over time. The results not only showed that microglia can effectively alleviate neurons from toxic protein burdens but that they also transfer mitochondria toward affected neurons via the same TNTs.

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"Next, the researchers investigated whether known genetic mutations associated with neurodegenerative diseases influenced the formation of tunnelling nanotubes and the TNT-based rescue mechanisms. They observed that mutations on the LRRK2 and Trem2 genes, respectively linked to Parkinson's disease and frontotemporal dementia, either reduced aggregate removal or compromised the delivery of functional mitochondria. Additionally, alterations linked to Parkinson's in gene Rac1 could also affect TNT formation and functionality.

"These results indicate new ways by which known genetic mutations may be contributing to neurodegenerative diseases. By disrupting TNT-mediated neuroprotective mechanisms, these genetic variants prevent microglia from supporting neurons effectively. Targeting these genes may provide an avenue to enhance TNT formation and activate transfer via these nanotubes, which may in turn help mitigate the progression of certain neurodegenerative diseases."

Comment: the microglia are similar to white blood cells elsewhere in the body tissues. The complexity of this arrangement implies design.