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Work hard, play hard: how sexually differentiated microglia work to shape social play and reproductive behavior
Olivia Sullivan1, Annie Vogel Ciernia1,2
1Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.
Abstract:
Microglia are brain-resident immune cells that play a critical role in synaptic pruning and circuit fine-tuning during development. In the adult brain, microglia actively survey their local environment and mobilize inflammatory responses to signs of damage or infection. Sex differences in microglial gene expression and function across the lifespan have been identified, which play a key role in shaping brain function and behavior. The levels of sex hormones such as androgens, estrogens, and progesterone vary in an age-dependent and sex-dependent manner. Microglia respond both directly and indirectly to changes in hormone levels, altering transcriptional gene expression, morphology, and function. Of particular interest is the microglial function in brain regions that are highly sexually differentiated in development such as the amygdala as well as the pre-optic and ventromedial hypothalamic regions. With a focus on hormone-sensitive developmental windows, this review compares male and female microglia in the embryonic, developing, and adult brain with a particular interest in the influence of sex hormones on microglial wiring of social, reproductive, and disordered behavior circuits in the brain.
Insights
Sex hormones influence microglia, the brain's immune cells, impacting development and behavior across the lifespan. This review examines sex differences in microglia and their role in shaping brain circuits.
Area of Science:
- Neuroimmunology
- Developmental Neuroscience
- Endocrinology
Background:
- Microglia are crucial for brain development, synaptic pruning, and immune surveillance.
- Sex differences in microglial gene expression and function impact brain development and behavior.
- Sex hormones (androgens, estrogens, progesterone) fluctuate with age and sex, influencing microglial activity.
Purpose of the Study:
- To compare male and female microglia across embryonic, developmental, and adult stages.
- To investigate the influence of sex hormones on microglial function and gene expression.
- To explore microglial roles in sexually differentiated brain regions and behavior circuits.
Main Methods:
- Comparative analysis of microglial characteristics in male and female brains.
- Focus on hormone-sensitive developmental periods.
- Review of existing literature on sex hormones and microglial function.
Main Results:
- Sex differences in microglia are evident from embryonic stages through adulthood.
- Sex hormones directly and indirectly modulate microglial transcriptional, morphological, and functional states.
- Microglia play a significant role in wiring circuits underlying social, reproductive, and behavioral functions.
Conclusions:
- Sex hormones are critical regulators of microglial development and function throughout life.
- Understanding sex-specific microglial responses to hormones is key to comprehending brain development and behavior.
- Further research into microglial-hormone interactions can illuminate mechanisms of social, reproductive, and behavioral disorders.
