Journal of Alzheimer's disease : JAD · 2023
Prodromal Glutamatergic Modulation with Riluzole Impacts Glucose Homeostasis and Spatial Cognition in Alzheimer's Disease Mice.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Findley Caleigh A, McFadden Samuel A, Cox MaKayla F, Sime Lindsey N, Peck Mackenzie R, Quinn Kathleen, Bartke Andrzej, Hascup Kevin N, Hascup Erin R
Аннотация
BACKGROUND: Prior research supports a strong link between Alzheimer's disease (AD) and metabolic dysfunction that involves a multi-directional interaction between glucose, glutamatergic homeostasis, and amyloid pathology. Elevated soluble amyloid-β (Aβ) is an early biomarker for AD-associated cognitive decline that contributes to concurrent glutamatergic and metabolic dyshomeostasis in humans and male transgenic AD mice. Yet, it remains unclear how primary time-sensitive targeting of hippocampal glutamatergic activity may impact glucose regulation in an amyloidogenic mouse model. Previous studies have illustrated increased glucose uptake and metabolism using a neuroprotective glutamate modulator (riluzole), supporting the link between glucose and glutamatergic homeostasis.
OBJECTIVE: We hypothesized that targeting early glutamatergic hyperexcitation through riluzole treatment could aid in attenuating co-occurring metabolic and amyloidogenic pathologies with the intent of ameliorating cognitive decline.
METHODS: We conducted an early intervention study in male and female transgenic (AβPP/PS1) and knock-in (APPNL - F/NL - F) AD mice to assess the on- and off-treatment effects of prodromal glutamatergic modulation (2-6 months of age) on glucose homeostasis and spatial cognition through riluzole treatment.
RESULTS: Results indicated a sex- and genotype-specific effect on glucose homeostasis and spatial cognition with riluzole intervention that evolved with disease progression and time since treatment.
CONCLUSION: These findings support the interconnected nature of glucose and glutamatergic homeostasis with amyloid pathology and petition for further investigation into the targeting of this relationship to improve cognitive performance.
OBJECTIVE: We hypothesized that targeting early glutamatergic hyperexcitation through riluzole treatment could aid in attenuating co-occurring metabolic and amyloidogenic pathologies with the intent of ameliorating cognitive decline.
METHODS: We conducted an early intervention study in male and female transgenic (AβPP/PS1) and knock-in (APPNL - F/NL - F) AD mice to assess the on- and off-treatment effects of prodromal glutamatergic modulation (2-6 months of age) on glucose homeostasis and spatial cognition through riluzole treatment.
RESULTS: Results indicated a sex- and genotype-specific effect on glucose homeostasis and spatial cognition with riluzole intervention that evolved with disease progression and time since treatment.
CONCLUSION: These findings support the interconnected nature of glucose and glutamatergic homeostasis with amyloid pathology and petition for further investigation into the targeting of this relationship to improve cognitive performance.