Biology subjects

Brandes, M. S.

Publications and source records attributed to Brandes, M. S..

2 recordsLinked to original sources

bioRxiv2024

Asiatic acid improves mitochondrial function, activates antioxidant response in the mouse brain and improves cognitive function in beta-amyloid overexpressing mice.

Extracts of the plant Centella asiatica can enhance mitochondrial function, promote antioxidant activity and improve cognitive deficits. Asiatic acid (AA) is one of the constituent triterpene compounds present in the plant. In this study we explore the effects of increasing concentrations of AA on brain mitochondrial function, antioxidant response and cognition in healthy mice and a single concentration of AA in the beta-amyloid overexpressing 5xFAD mouse line. Associative memory and overall activity were assessed. Hippocampal mitochondrial bioenergetics and the expression of mitochondrial and antioxidant response genes was determined. In the 5xFAD line, total beta-amyloid plaque burden after AA treatment was also evaluated. In healthy mice, we report dose responsive effects of increasing concentrations of AA on enhanced associative memory and a dose dependent increase in basal and maximal mitochondrial respiration, mitochondrial gene expression and antioxidant gene expression. Results from the highest AA dose (1% AA) were similar to what was observed with CAW. The high AA dose was then evaluated in the context of A{beta} accumulation in 5xFAD mice. Improvements in mitochondrial and antioxidant response genes were favored in females over males without significant alleviation of A{beta} plaque burden.

neuroscience↗

bioRxiv2024

The CD74 inhibitor DRhQ improves cognition and mitochondrial function in 5xFAD mouse model of Aβ accumulation

Neuroinflammation and mitochondrial dysfunction are early events in Alzheimers disease (AD) and contribute to neurodegeneration and cognitive impairment. Evidence suggests that the inflammatory axis mediated by macrophage migration inhibitory factory (MIF) binding to its receptor, CD74, plays an important role in many central nervous system (CNS) disorders like AD. Our group has developed DRhQ, a novel CD74 binding construct that competitively inhibits MIF binding, blocks T-cell and macrophage activation and migration into the CNS, enhances anti-inflammatory microglia cell numbers and reduces pro-inflammatory gene expression. Here we evaluate its effects in {beta}-amyloid (A{beta}) overexpressing mice. 5xFAD mice and their wild type littermates were treated with DRhQ (100 {micro}g) or vehicle for 4 weeks. DRhQ improved cognition and cortical mitochondrial function in both male and female 5xFAD mice. A{beta} plaque burden in 5xFAD animals were not robustly impacted by DRhQ treatment nor was microglial activation, although in the hippocampus there was some evidence of a reduction in female 5xFAD mice. Future studies are needed to confirm this possible sex-dependent response on microglial activation as well as to optimize the dose, and timing of DRhQ treatment and gain a better understanding of its mechanism of action.

neuroscience↗