Leukotriene signaling as molecular correlate for cognitive heterogeneity in aging: an exploratory study

白三烯信号作为衰老认知异质性的分子关联:一项探索性研究

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作者:Heike Mrowetz #, Mohamed H Kotob #, Jennifer Forster #, Iren Aydin, Michael Stefan Unger, Jana Lubec, Ahmed M Hussein, Jovana Malikovic, Daniel Daba Feyissa, Volker Korz, Harald Höger, Gert Lubec, Ludwig Aigner

Discussion

We conclude that 5-Lox expressing microglia potentially contribute to the age-related cognitive decline in the brain, while low levels of the LT system might indicate and foster higher cognitive functions and eventually cognitive reserve and resilience in aging.

Methods

Here, we analyzed the brain's expression of key components of the LT synthesis pathway, i.e., the expression of 5-lipoxygenase (5-Lox), the key enzyme in LT production, and 5-lipoxygenase-activating protein (FLAP) in young and aged rats. More specifically, we used a cohort of rats, which, although grown up and housed under identical conditions, developed into aged cognitively unimpaired and aged cognitively impaired traits.

Results

Expression of 5-Lox was increased within the brain of aged rats with the highest levels detected in cognitively impaired animals. The number of microglia cells was higher in the aged compared to the young brains with, again, the highest numbers of 5-Lox expressing microglia in the aged cognitively impaired rats. Remarkably, lower cognitive scores in the aged rats associated with higher numbers of 5-Lox positive microglia in the animals. Similar data were obtained for FLAP, at least in the cortex. Our data indicate elevated levels of the LT system in the brain of cognitively impaired animals.

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