Abstract:
:As the resident macrophage of the central nervous system, microglia are thought to contribute to Alzheimer's disease (AD) pathology through lack of neuroprotection. The role of immune dysfunction in AD may be due to disruption of regulatory signals for the activation of microglia that may occur early in development. We hypothesized that early toxicant exposure would systematically activate microglia, possibly reversing the pathological severity of AD. Offspring of a triple transgenic murine model for AD (3×TgAD) were exposed to a model neurotoxicant, lead acetate, from postnatal days (PND) 5-10. Our results indicated that female mice exposed to Pb had a greater and earlier incidence of amyloid burden within the hippocampus, coinciding with decreased markers of microglial activation at PND 50. Pb-exposed males had increased microglial activation at PND 50, as evidence by CD11b expression and microglial abundance, with no significant increase in amyloid burden at that time. There was greater amyloid burden at PND 90 and 180 in both male and female mice exposed to Pb compared with control. Together, these data suggest that activated microglia are neuroprotective against amyloid accumulation early in AD pathology, and that early exposure to Pb could increase susceptibility to later-life neurodegeneration. Likewise, females may be more susceptible to early-life microglial damage, and, subsequently, AD. Further investigation into the sex biased mechanisms by which microglial activation is altered by an early-life immune insult will provide critical insight into the temporal susceptibility of the developing neuroimmune system and its potential role in AD etiopathology.
journal_name
J Dev Orig Health Disjournal_title
Journal of developmental origins of health and diseaseauthors
vonderEmbse AN,Hu Q,DeWitt JCdoi
10.1017/S2040174417000277subject
Has Abstractpub_date
2017-08-01 00:00:00pages
493-501issue
4eissn
2040-1744issn
2040-1752pii
S2040174417000277journal_volume
8pub_type
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journal_title:Journal of developmental origins of health and disease
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journal_title:Journal of developmental origins of health and disease
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journal_title:Journal of developmental origins of health and disease
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journal_title:Journal of developmental origins of health and disease
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journal_title:Journal of developmental origins of health and disease
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journal_title:Journal of developmental origins of health and disease
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