Title:Microdose Lithium NP03 Diminishes Pre-Plaque Oxidative Damage and Neuroinflammation in a Rat Model of Alzheimer’s-like Amyloidosis
Volume: 15
Issue: 13
关键词:
阿尔茨海默病，氧化应激，炎症，微量锂，小胶质细胞，TREM 2。
摘要: Background: Microdose lithium is protective against Alzheimer’s disease (AD), although the
precise mechanisms through which its protective effects are conferred remain unclear.
Objective: To further examine the effects during the earliest stages of Aβ pathology, we evaluated
whether NP03, a microdose lithium formulation, modulates Aβ-mediated oxidative damage and neuroinflammation
when applied to a rat transgenic model of AD-like amyloidosis overexpressing amyloid precursor
protein (APP).
Method: McGill-R-Thy1-APP transgenic rats and wild-type littermates were treated with NP03 or vehicle
formulation for 8 weeks beginning at 3 months of age - a phase preceding Aβ plaque deposition in
the transgenic rats.
Results: Oxidative and nitrosative stress markers, protein-bound 4-hydroxynonenal (HNE) and proteinresident
3-nitrotyrosine (3-NT), inflammatory cytokines production, as well as microglial recruitment
towards Aβ-burdened neurons were assayed. NP03 significantly decreased cerebral HNE and 3-NT, and
reduced production of pro-inflammatory cytokines in McGill-R-Thy1-APP transgenic rats. NP03 further
reduced expression of microglia surface receptor Trem2 and led to a corresponding reduction in microglia
recruitment towards Aβ-burdened neurons in the CA1 region of the hippocampus.
Conclusion: These results suggest that NP03 may function to slow the AD-like pathology in part by
modifying oxidative/nitrosative damage and neuroinflammation, raising the possibility that low doses of
microencapsulated lithium might be of therapeutic-preventive value during very early or preclinical AD.
