β-Hydroxybutyrate preferentially enhances neuron over astrocyte respiration while signaling cellular quiescence.

While ketone bodies support overall brain energy metabolism, it is increasingly clear specific brain cell types respond differently to ketone body availability. Here, we characterized how SH-SY5Y neuroblastoma cell, primary neuron, and primary astrocyte bioenergetics and nutrient sensing pathways respond to β-hydroxybutyrate (βOHB). SH-SY5Y cells and primary neurons, but not astrocytes, exposed to βOHB increased respiration and decreased PI3K-Akt-mTOR signaling.

A ketogenic diet differentially affects neuron and astrocyte transcription.

Ketogenic diets (KDs) alter brain metabolism. Multiple mechanisms may account for their effects, and different brain regions may variably respond. Here, we considered how a KD affects brain neuron and astrocyte transcription.

Mitochondrial DNA Manipulations Affect Tau Oligomerization.

Background: Mitochondrial dysfunction and tau aggregation occur in Alzheimer's disease (AD), and exposing cells or rodents to mitochondrial toxins alters their tau.

Objective: To further explore how mitochondria influence tau, we measured tau oligomer levels in human neuronal SH-SY5Y cells with different mitochondrial DNA (mtDNA) manipulations.

Methods: Specifically, we analyzed cells undergoing ethidium bromide-induced acute mtDNA depletion, ρ0 cells with chronic mtDNA depletion, and cytoplasmic hybrid (cybrid) cell lines containing mtDNA from AD subjects.

Mitochondria in Alzheimer's disease and their potential role in Alzheimer's proteostasis.

Alzheimer's disease (AD) is a progressive brain disorder characterized by memory loss and the accumulation of two insoluble protein aggregates, tau neurofibrillary tangles and beta-amyloid plaques. Widespread mitochondrial dysfunction also occurs and mitochondria from AD patients display changes in number, ultrastructure, and enzyme activities. Mitochondrial dysfunction in AD presumably links in some way to its other disease characteristics, either as a cause or consequence.

Effects of Microglial Cytokines on Alzheimer's Disease-Related Phenomena.

Recent association studies indicate several genes highly expressed by microglia influence Alzheimer's disease (AD) risk, which suggests microglial function contributes to this disease. Here, we evaluated how one component of microglial function, cytokine release, affects AD-related phenomena. First, we used a 3-hour lipopolysaccharide (LPS) treatment to activate mouse BV2 microglial cells.

A bioenergetics systems evaluation of ketogenic diet liver effects.

Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body production. To further evaluate how ketogenic diets affect hepatocyte bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice maintained for 1 month on a ketogenic or standard chow diet. Compared with the standard diet, the ketogenic diet increased cytosolic and mitochondrial protein acetylation and also altered protein succinylation patterns.

Mitochondria-Derived Damage-Associated Molecular Patterns in Neurodegeneration.

Inflammation is increasingly implicated in neurodegenerative disease pathology. As no acquired pathogen appears to drive this inflammation, the question of what does remains. Recent advances indicate damage-associated molecular pattern (DAMP) molecules, which are released by injured and dying cells, can cause specific inflammatory cascades.

Extracellular Mitochondria and Mitochondrial Components Act as Damage-Associated Molecular Pattern Molecules in the Mouse Brain.

Mitochondria and mitochondrial debris are found in the brain's extracellular space, and extracellular mitochondrial components can act as damage associated molecular pattern (DAMP) molecules. To characterize the effects of potential mitochondrial DAMP molecules on neuroinflammation, we injected either isolated mitochondria or mitochondrial DNA (mtDNA) into hippocampi of C57BL/6 mice and seven days later measured markers of inflammation. Brains injected with whole mitochondria showed increased Tnfα and decreased Trem2 mRNA, increased GFAP protein, and increased NFκB phosphorylation.