Mitochondrial Quality Control in Microglia in the Aging Brain

Microglia are innate immune cells of the central nervous system, similar to macrophages elsewhere in the body. These cells become more inflammatory and dysfunctional with age, and this is implicated in the onset and progression of neurodegenerative conditions. Chronic inflammation is disruptive of tissue function, and in the brain is connected with a range of pathological mechanisms. Here, researchers discuss the loss of autophagy and related mitochondrial quality control characteristic of age, and how this might affect microglia. Inflammation and mitochondrial dysfunction are connected, one of the many ways in which age-related decline can provoke chronic, unresolved inflammation in tissues throughout the body.

Microglia, characterized by responding to damage, regulating the secretion of soluble inflammatory mediators, and engulfing specific segments in the central nervous system (CNS), function as key immune cells in the CNS. Emerging evidence suggests that microglia coordinate the inflammatory responses in CNS system and play a pivotal role in the pathogenesis of age-related neurodegenerative diseases (NDDs). Remarkably, microglia autophagy participates in the regulation of subcellular substances, which includes the degradation of misfolded proteins and other harmful constituents produced by neurons. Therefore, microglia autophagy regulates neuronal homeostasis maintenance and process of neuroinflammation.

Here, we provide an overview of the relationship between microglia autophagy and NDDs. The onset and progression of NDDs are associated with the accumulation of abnormal substances in the nervous system. Recent studies revealed that microglia autophagy removes harmful substances and abnormal aggregates produced by neurons in the nervous system and acts as a neuroprotective agent, which can help treat NDDs or control their progression. Meantime, manipulation of microglia autophagy also interrupts neuroinflammation in NDDs, maintain a state of equilibrium, and prevent disease progression. Therefore, the balance between microglia autophagy and neuroinflammation is of critical importance in NDDs.

Noticeably, potential drugs such as kaempferol, melatonin, and spermidine have been shown to balance microglia autophagy and neuroinflammation in NDDs. However, the mechanisms of interaction between microglia autophagy and neurons have not been sufficiently elucidated, such as how microglia autophagy remove toxic substances produced by neurons or glial cells or how microglia autophagy counteract abnormal neuronal death. More in-depth studies remain to be completed in this area.



Should we be careful about supplementing Spermadine?

"This is why spermidine is a double-edged sword where in excess, it provokes O2- anion production, and in scarcity, it leads to higher ROS levels."
" Finally, we demonstrate that while RNA-bound spermidine inhibits iron oxidation, free spermidine interacts and oxidizes the iron to evoke superoxide radicals directly."

Posted by: august33 at May 30th, 2023 9:13 PM

Review of mostly genetically modified rodent studies, does it apply to humans?

Morphological Differences: Human microglia tend to have larger cell bodies and longer processes compared to mouse microglia. They exhibit more complex and ramified structures, suggesting increased surveillance capabilities and interactions with surrounding neurons.

Gene Expression Profiles: Studies have revealed significant differences in the gene expression profiles between human and mouse microglia. There are species-specific gene expression patterns, indicating that certain functions or pathways may be regulated differently. For example, human microglia display a distinct gene expression signature associated with neurodegenerative diseases.

Lifespan and Turnover: Microglia turnover and lifespan differ between humans and mice. In mice, microglia undergo more rapid turnover, with a lifespan of weeks to months. In contrast, human microglia are long-lived cells that can persist for years or even decades.

Response to Pathogens and Inflammation: Human microglia exhibit a more robust and diverse response to pathogens and inflammation compared to mouse microglia. Human microglia are capable of mounting stronger inflammatory responses and releasing a wider range of cytokines and chemokines, suggesting a more complex immune response.

Aging and Neurodegeneration: Aging-related changes and neurodegenerative diseases may also differ between humans and mice. The progression and manifestation of neurodegenerative diseases such as Alzheimer's or Parkinson's may not fully recapitulate the human condition in mouse models due to species-specific differences in microglia behavior and disease mechanisms.

Environmental Factors: Microglia responses can be influenced by environmental factors, and there may be variations in microglia behavior due to differences in the brain environment between humans and mice. Environmental cues, such as the presence of certain neurotransmitters or growth factors, can modulate microglial function differently across species.

Posted by: Jones at May 31st, 2023 2:52 AM
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