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Two-photon Imaging of Microglial Processes' Attraction Toward ATP or Serotonin in Acute Brain Slices
Published on: January 31, 2019
Mitochondria are absent from microglial processes performing surveillance, chemotaxis, and phagocytic engulfment
Alicia N Pietramale1, Xhoela Bame1, Megan E Doty1
1Department of Biological Sciences, Dartmouth College, Hanover, NH, USA.
Abstract:
Microglia continually surveil the brain allowing for rapid detection of tissue damage or infection. Microglial metabolism is linked to tissue homeostasis, yet how mitochondria are subcellularly partitioned in microglia and dynamically reorganize during surveillance, injury responses, and phagocytic engulfment in the intact brain are not known. Here, we performed intravital imaging and ultrastructural analyses of microglia mitochondria in mice and human tissue, revealing that microglial processes diverge in their mitochondrial content, with some containing multiple mitochondria while others are completely void. Microtubules and hexokinase 2 mirror this uneven mitochondrial distribution indicating that these cytoskeletal and metabolic components are linked to mitochondrial organization in microglia. Microglial processes that engage in minute-to-minute surveillance typically do not have mitochondria. Moreover, unlike process surveillance, mitochondrial motility does not change with animal anesthesia. Likewise, the processes that acutely chemoattract to a lesion site or initially engage with a neuron undergoing programmed cell death do not contain mitochondria. Rather, microglia mitochondria have a delayed arrival into the responding cell processes. Thus, there is subcellular heterogeneity of mitochondrial partitioning. Moreover, microglial processes that surveil and acutely respond to damage do not contain mitochondria.
Insights
Microglia, immune cells in the brain, show uneven mitochondrial distribution. Surveillance and acute injury response processes lack mitochondria, indicating specialized subcellular partitioning for brain immune cell function.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are crucial for brain surveillance and detecting damage or infection.
- Microglial metabolism and mitochondrial function are vital for tissue homeostasis.
- The dynamic reorganization and subcellular partitioning of mitochondria in microglia remain largely unknown.
Purpose of the Study:
- To investigate the subcellular localization and dynamic reorganization of mitochondria within microglia during brain surveillance, injury response, and phagocytosis.
- To understand the relationship between cytoskeletal and metabolic components with mitochondrial distribution in microglia.
Main Methods:
- Intravital imaging in mice.
- Ultrastructural analyses of microglia mitochondria in mice and human tissue.
Main Results:
- Microglial processes exhibit heterogeneous mitochondrial content; some are rich in mitochondria, while others are devoid.
- Microtubules and hexokinase 2 correlate with this uneven mitochondrial distribution.
- Mitochondria are typically absent from microglial processes involved in surveillance and acute responses to lesions or neuronal cell death.
- Mitochondria show a delayed arrival into responding microglial processes.
Conclusions:
- Microglia display significant subcellular heterogeneity in mitochondrial partitioning.
- Mitochondria are not present in microglial processes during initial surveillance or acute damage response, suggesting a specialized role and delayed mobilization.
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