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P1‐204: A NOVEL PHARMACOLOGICAL INTERVENTION TO NEUROINFLAMMATORY OUTCOMES OF AIR POLLUTION: THE GAMMA SECRETASE MODULATOR BPN‐15606 ATTENUATED MICROGLIAL AND AMYLOID INDUCTION BY URBAN NANO‐PARTICULATE (NPM) IN YOUNG MALE C57BL/6J MICE
Author(s) -
D'agostino Carla,
Cacciottolo Mafalda,
Shirmohammadi Farimah,
Sioutas Constantinos,
Wagner Steven L.,
Tanzi Rudolph E.,
Morgan Todd E.,
Finch Caleb E.
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.759
Subject(s) - microglia , hippocampal formation , pharmacology , amyloid (mycology) , amyloid precursor protein secretase , senile plaques , chemistry , neuroinflammation , amyloid precursor protein , medicine , neuroscience , alzheimer's disease , inflammation , biology , pathology , disease
transcriptomic overlaps with human aging and Alzheimer’s disease. Conclusions: Overall, the present study, for the first time, shows that in addition to the widely recognized astrocytic EAAT2, neuronal EAAT2 also plays a role in hippocampus-dependent memory. Furthermore, astrocytic rather than neuronal EAAT2 deficiency in the hippocampus is transcriptionally more closely associated with human aging and AD. The study further implicates glutamatergic dyshomeostasis in inflammation and neural plasticity in aging and AD, highlights the distinct signaling mechanisms mediated by neuronal and astrocytic EAAT2 and EAAT2 as a potential therapeutic target in aging and AD.