Acute Inflammatory Events Attenuate High-Sucrose Diet-Induced Spatial Learning Deficits in Wild-Type Female Mice

Author(s): Lane K. Bekar

It is known that diabetic and chronic inflammatory conditions can increase the risk of Alzheimer’s disease (AD)-like neurodegeneration. However, in contrast to chronic inflammatory conditions, transient low-grade inflammation may confer neuroprotection. As certain elements of the diabetic/pre-diabetic state may sensitize the brain to inflammatory insult (i.e. excess glucocorticoid activity), there is reason to believe that obesogenic factors may allow ordinarily benign inflammatory stimuli to precipitate the chronic inflammatory state oft observed in neurodegenerative conditions. Also, given that most AD research utilizes male animal models despite increased prevalence of AD among women, we sought to characterize elements of the established (in males) high-sucrose model of neurodegeneration, for the first time, in reproductively normal (pre-menopausal) female mice. A high-sucrose diet (20% of the drinking water) was combined with low-grade systemic intraperitoneal lipopolysaccharide (LPS) injections (0.1 mg/kg; 1x/month over 3 months) over seven months in reproductively normal female wild-type mice (C57Bl/6; n=10/group). Although a deleterious synergistic effect was hypothesized, low-dose LPS proved to protect against high sucrose diet-induced pathologies in female wild-type mice. Results from our high-sucrose group confirmed that a high-sucrose diet contributes to neurodegenerative processes in wild-type females, as evidenced by exaggerated glucocorticoid expression, spatial learning deficits, irregularities within the insulin pathway, and trends toward increased β-amyloid production and Tau phosphorylation. While LPS had little to no effect in isolation, it exerted a protective influence when added to animals sustained on a high-sucrose diet. Corticosterone homeostasis, and levels of amyloid-β (Aβ) and pTau were rescued following addition of LPS. The work presented supports a role for the high-sucrose diet in the induction of neurodegenerative processes in female wild-type mice and highlights a seemingly protective role for low-grade transient inflammation against dietary-insult.

© 2016-2024, Copyrights Fortune Journals. All Rights Reserved