Abstract
BackgroundLipocalin 2 (Lcn2) is an acute-phase protein implicated in multiple neurodegenerative conditions. Interestingly, both neuroprotective and neurodegenerative effects have been described for Lcn2. Increased Lcn2 levels were found in human post-mortem Alzheimer (AD) brain tissue, and in vitro studies indicated that Lcn2 aggravates amyloid-β-induced toxicity. However, the role of Lcn2 has not been studied in an in vivo AD model. Therefore, in the current study, the effects of Lcn2 were studied in the J20 mouse model of AD.MethodsJ20 mice and Lcn2-deficient J20 (J20xLcn2 KO) mice were compared at the behavioral and neuropathological level.ResultsJ20xLcn2 KO and J20 mice presented equally strong AD-like behavioral changes, cognitive impairment, plaque load, and glial activation. Interestingly, hippocampal iron accumulation was significantly decreased in J20xLcn2 KO mice as compared to J20 mice.ConclusionsLcn2 contributes to AD-like brain iron dysregulation, and future research should further explore the importance of Lcn2 in AD.
Highlights
Lipocalin 2 (Lcn2) is an acute-phase protein implicated in multiple neurodegenerative conditions
Despite an increased time spent in the center zone of the open field in lipocalin 2 knock-out (Lcn2 KO) mice compared to WT mice (p < 0.05, Additional file 1: Figure S4A), no differences were found in the latency to enter the center zone of the open field (Additional file 1: Figure S4B), in the time spent on the open or closed arms in the elevated-plus maze (EPM) (Additional file 1: Figure S4C, D) or in the number of EPM arm entries
We report that J20 and Lcn2-deficient J20 (J20xLcn2 KO) mice at 12 months of age show severe Alzheimer’s disease (AD)-like behavioral changes, cognitive impairment, plaque formation, and glial activation
Summary
Lipocalin 2 (Lcn2) is an acute-phase protein implicated in multiple neurodegenerative conditions. Both neuroprotective and neurodegenerative effects have been described for Lcn. Neuroinflammation has been recognized to play an important role in AD, and involves chronic activation of microglia and astrocytes in brain regions affected by AD pathology [1,2,3]. While microglia- and astrocyte-mediated immune responses may initially be neuroprotective, Iron dysregulation is known to play an important part in AD pathology [11]. Iron accumulation occurs in brain regions affected by AD pathology, in plaques and cell types including neurons and microglia [12,13,14,15]. Iron accumulation may contribute significantly to AD pathology by promoting Aβ aggregation, enhancing further pro-inflammatory processes, disturbing mitochondrial respiration, stimulating oxidative stress, and inducing ferroptosis [11, 16].
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