Reference - Detail
| RRC ID | 87297 |
|---|---|
| Author | Findley CA, McFadden SA, Cox MF, Sime LN, Peck MR, Quinn K, Bartke A, Hascup KN, Hascup ER. |
| Title | Prodromal Glutamatergic Modulation with Riluzole Impacts Glucose Homeostasis and Spatial Cognition in Alzheimer's Disease Mice. |
| Journal | J Alzheimers Dis |
| Abstract |
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. |
| Volume | 94(1) |
| Pages | 371-392 |
| Published | 2023-1-1 |
| DOI | 10.3233/JAD-221245 |
| PII | JAD221245 |
| PMID | 37248899 |
| PMC | PMC10357216 |
| MeSH | Alzheimer Disease* / drug therapy Alzheimer Disease* / genetics Alzheimer Disease* / metabolism Amyloid beta-Peptides / metabolism Amyloid beta-Protein Precursor / genetics Amyloid beta-Protein Precursor / metabolism Animals Cognition Disease Models, Animal Female Glucose / metabolism Homeostasis Humans Male Mice Mice, Inbred C57BL Mice, Transgenic Riluzole / pharmacology Riluzole / therapeutic use |
| Resource | |
| Mice | RBRC06343 |