X, but not Y, Chromosomal Complement Contributes to Stroke Sensitivity in Aged Animals.
Shaohua Qi1, Conelius Ngwa1, Abdullah Al Mamun1
1Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, McGovern Medical School, 6431 Fannin Street, Houston, TX, 77030, USA.
Translational Stroke Research
|July 29, 2022
Summary
The number of X chromosomes, not the Y chromosome, influences stroke severity in aged mice. Having two X chromosomes increases inflammation and worsens stroke outcomes.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Post-menopausal women experience higher stroke mortality than men.
- Sex chromosomes are implicated in stroke sensitivity, but the specific roles of X and Y chromosomes remain unclear.
Purpose of the Study:
- To investigate the differential effects of X versus Y chromosomes on stroke outcomes.
- To determine if the number of X chromosomes influences stroke sensitivity and associated inflammatory responses.
Main Methods:
- Utilized the XY* mouse model with four genotypes (XX, XO, XY, XXY) subjected to middle cerebral artery occlusion.
- Assessed infarct volume, behavioral deficits, microglial activation, leukocyte infiltration, plasma cytokine levels, and expression of X-linked genes (KDM6A, KDM5C).
Main Results:
- Mice with two X chromosomes (XX, XXY) exhibited worse stroke outcomes compared to those with one X chromosome (XO, XY).
- Two X chromosomes correlated with increased microglial activation, leukocyte infiltration, elevated plasma cytokines, and higher expression of KDM6A and KDM5C.
- Differences between XX vs. XXY and XO vs. XY aged mice were minimal, suggesting the number of X chromosomes is a key factor.
Conclusions:
- The number of X chromosomes, rather than the Y chromosome, significantly mediates stroke sensitivity in aged mice.
- X chromosome dosage may influence stroke outcomes through inflammatory pathways involving X-linked genes like KDM6A and KDM5C.
