Increase the amyloid pathology in meningitis-induced cognitive impairment: sex differences

Abstract

Background

Pneumococcal meningitis is a type of meningitis that may face long-term neurological complications, leading to the hypothesis that it might contribute to the deposition of beta-amyloid (Aβ) and predispose individuals to Alzheimer’s pathology.

Method

Male and female APP/PS1 mice, 50 days old, were divided into control (n = 5) and meningitis (n = 6). Under anesthesia, an intracisternal injection of either artificial cerebrospinal fluid (CSF) as a placebo or 5 × 10⁹ colony-forming units (CFU) of S. pneumoniae suspension was injected. Meningitis was confirmed through culture incubation. The Open Field Test (OFT) and Novel Object Recognition (NOR) tasks were conducted when the mice reached 180 days of age; after this, the hippocampus and prefrontal cortex (PFC) were stained to be evaluated by immunofluorescence.

Result

Mice of both sexes experiencing meningitis displayed cognitive impairment (p < 0,001) evaluated for NOR, but the distribution of Aβ burden differed between males and females. Males exhibited elevated Aβ predominantly in the hippocampus (p < 0,05), while females showed heightened Aβ levels exclusively in the PFC (p < 0,05). Interestingly, only females with meningitis showed increased levels of IBA-1, a marker for microglial reactivity, in both the hippocampus (p = 0,0048) and PFC (p = 0,0023) compared to their controls.

Conclusion

The distinct patterns observed in Aβ distribution and microglial activation between sexes suggest a potential association, indicating that meningitis can induce elevated Aβ deposition, with microglia potentially playing a role in this divergent response.