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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
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Neonatal testosterone voids sexually differentiated microglia morphology and behavior
Carla Filipa Simões-Henriques1,2,3, A Catarina Rodrigues-Neves1,2,3, Fábio J Sousa1,2,3
1Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Frontiers in Endocrinology
|March 17, 2023
Summary
Sex differences in brain immune cell (microglia) morphology emerge during adolescence, influenced by testosterone. These changes correlate with behavioral responses to anxiety, with early testosterone exposure impacting adult outcomes.
Area of Science:
- Neuroimmunology
- Developmental Neuroscience
- Behavioral Endocrinology
Background:
- Immunity plays a role in psychiatric disorders like anxiety, with microglia (brain immune cells) adapting morphologically to stress.
- Sexually differentiated microglia morphology exists in adult rodents in brain regions linked to anxiety.
- The timing of these sex differences and their relation to behavior and hormonal influences remain unclear.
Purpose of the Study:
- To determine if microglia morphology differences are present at birth or develop postnatally.
- To investigate the impact of postnatal testosterone on microglia morphology and anxiety-related behavior.
- To elucidate the developmental trajectory of sex differences in microglia and behavior.
Main Methods:
- Comparative morphological analysis of microglia across different developmental stages (birth, adolescence, adulthood) in rodents.
- Assessment of anxiety-related behaviors in response to anxiogenic stimuli.
- Experimental manipulation using neonatal testosterone administration in female rodents.
Main Results:
- Sex differences in microglia morphology are not present at birth but emerge during adolescence, characterized by increased complexity in males.
- Adolescent females treated neonatally with testosterone display masculinized microglia and behavior.
- A sex-determined shift in microglia complexity occurs between adolescence and adulthood, which is partially reversed by testosterone administration, shifting towards a male phenotype.
Conclusions:
- Postnatal testosterone influences the development of sex differences in microglia morphology and anxiety-related behaviors.
- Microglia morphology undergoes significant sex- and age-dependent changes during development.
- Early life testosterone exposure can have lasting effects on neuroimmune profiles and behavior.
