Moca EN, Lecca D, Hope KT, Etienne F, Schaler AW, Espinoza K, Chappell MS, Gray DT, Tweedie D, Sidhu S, Masukawa L, Sitoy H, Mathew R, Saban DR, Greig NH, De Biase LM. Microglia Drive Pockets of Neuroinflammation in Middle Age. J Neurosci. 2022 May 11;42(19):3896-3918. Epub 2022 Apr 8 PubMed.
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University of Texas Health Science Center at Houston
Baylor College of Medicine
This is a thorough and meticulous study of microglial changes during the physiological aging process. Its strength comes from the keen observations of distinct microglial behaviors by brain region. A panel of complementary analyses revealed that microglia in both the VTA and SNc exhibit earlier age-related changes in morphology and inflammatory pathways than in other brain regions, and that striking lysosomal changes are likely connected to these changes.
Overall, the study convincingly highlights the complexity of microglial states. This is not necessarily restricted to overt CNS disease, but is apparently gained progressively and innately during normal brain aging.
It will be quite interesting to further characterize the material content enveloped by the CD68+ structures in microglia and investigate the significance of such aberrant formation. Many immune pathways signal through the endolysosomal compartment, thus such age-related intracellular complexity may play a role in initiating innate immune cascades and promoting microglia proliferation. Whether some or all of the adaptive changes in microglia contribute to the declined circuit function in aging would be import to illuminate. The interesting findings from this study undoubtedly invites future inquiries.
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