Sex differences in microglia function in aged rats underlie vulnerability to cognitive decline.

Area of Science:

• Neuroscience
• Immunology
• Gerontology

Background:

• Aging is linked to increased inflammation ('inflammaging') and reduced immune response effectiveness.
• Significant sex differences exist in immune function, potentially impacting aging processes and cognitive health.

Purpose of the Study:

• To investigate if sex differences in immune aging mediate sex differences in cognitive decline.
• To explore the neuroinflammatory and behavioral consequences of immune stimulation in aged male and female rats.

Main Methods:

• Aged male and female rats were subjected to peripheral immune stimulation with lipopolysaccharide (LPS).
• Molecular, cellular, and behavioral outcomes, including cognitive function and neuroinflammation, were assessed.
• Transcriptomic and flow cytometry analyses identified changes in brain immune cell populations.

Main Results:

• Aged male rats treated with LPS exhibited cognitive impairment and heightened neuroinflammatory responses compared to adult males.
• Aged female rats did not show similar age-related deficits following LPS treatment.
• Ovariectomized aged females remained resistant to inflammation-induced memory deficits, suggesting ovarian hormones are not essential for this protection.

Conclusions:

• Males exhibit amplified inflammatory priming with age, contributing to age-associated cognitive decline.
• Sexual dimorphism is evident in aging mechanisms, impacting neuroinflammation and cognition.
• Sex is a critical factor to consider when developing therapies for aging and neuroinflammation.