Pyrroloquinoline Quinone Enhances Cognition of Neuroinflammatory Alzheimer’s Disease Mouse Model via Mitochondrial Biogenesis Regulation

Abstract

Background: Mitochondrial biogenesis has been recently implicated to play an important role in Alzheimer’s disease (AD). Recently it has been reported that brains of AD patients show reduced expression in major genes and proteins such as PGC-1α involved in mitochondrial biogenesis. This led to the idea that enhancing mitochondrial biogenesis in AD, might represent a plausible strategy for AD treatment. Pyrroloquinoline quinone (PQQ) has been recently implicated in enhancing cognitive functions during aging; however, its effect on mitochondrial biogenesis in neuroinflammatory AD mouse model was not previously examined. Objective: The aim of this project was to test the cognitive enhancement effect of PQQ in a neuroinflammatory mouse model mimicking AD, and whether PQQ is able to activate mitochondrial biogenesis in brains of our AD mouse model. Methods: Neuroinflammatory AD mouse model was developed by Lipopolysaccharide (250 g kg-1 body weight, i.p) injection for 7 days, followed by daily PQQ treatment (10 mg kg-1 body weight) on days 4-7. Cognitive functions were assessed using Y-Maze, Water-Maze and object recognition tests. Neurodegeneration was evaluated using H&E. Finally, mitochondrial proteins were measured using immunohistochemistry. Results: PQQ treatment improved spatial recognition and working memory. PQQ treated mice brains showed decreased levels of neurodegeneration. Moreover, their brains showed greater amounts of both PGC-1α and the mitochondrial-membrane-bound protein cytochrome-c, indicating enhancement of mitochondrial biogenesis. Conclusion: This study demonstrates the ability of PQQ to improve memory in neuroinflammatory AD model via enhancing mitochondrial biogenesis, which may represent an alternative mechanistic approach for treating AD.