Developmental Neuroscience Commons^™

Micu2 Controls Mitochondrial Calcium Signaling And Migration In Neurons During Development, Elena Berezhnaya, Benjamín Cartes-Saavedra, Raghavendra Singh, Macarena Rodríguez-Prados, Orly Reiner, Fowzan S Alkuraya, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Neurological disorders are linked to mitochondrial dysfunction and calcium overload. Mitochondrial calcium uptake is mediated by the mitochondrial calcium uniporter (mtCU), regulated by MICU1, which can be either homodimerized or heterodimerized with MICU2 or MICU3. Though MICU2 is scarce in the adult brain, MICU2 loss in patients leads to a neurodevelopmental disorder. We hypothesized that MICU2 is required for developmental calcium signaling and neuronal migration. MICU2 is present in the developing mouse brain but disappears by maturation, contrasting with other mtCU subunits that increase. MICU2 loss in mice does not affect cytoplasmic calcium but augments the mitochondrial matrix calcium rise …

Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander

Student Theses and Dissertations

Aerobic metabolism is known to generate damaging ROS, particularly hydrogen peroxide. Reactive oxygen species (ROS) are highly reactive molecules containing oxygen that have the potential to cause damage to cells and tissues in the body. ROS are highly reactive atoms or molecules that rapidly interact with other molecules within a cell. Intracellular accumulation can result in oxidative damage, dysfunction, and cell death. Due to the limitations of H₂O₂ (hydrogen peroxide) detectors, other impacts of ROS exposure may have been missed. HyPer7, a genetically encoded sensor, measures hydrogen peroxide emissions precisely and sensitively, even at sublethal levels, during …

Early Developmental Exposure To Δ9-Tetrahydrocannabinol Causes Latent Behavioral, Growth, And Bioenergetic Effects In Danio Rerio, Astra Hahm

Honors Theses

Early developmental exposure to Δ9-tetrahydrocannabinol causes latent behavioral, growth, and bioenergetic effects in Danio rerio

(Under the direction of Dr. Kristine Willett)

Δ9-tetrahydrocannabinol (Δ9-THC) is used during pregnancy to mitigate symptoms such as nausea, pain, and insomnia. It is established that Δ9-THC exposure early in life causes adverse effects in children’s development including behavioral disorders. Our goal was to determine the latent and generational impacts on growth, behavior, and mitochondrial bioenergetics following exposure to Δ9-THC. Wildtype (5D) zebrafish were exposed to 0 (0.05% DMSO), 0.08, 0.4, or 1 µM Δ9-THC from 6-96 hours post-fertilization (hpf), then subsequently raised in clean …

Oxidative Stress Alters Mitochondrial Homeostasis In Isolated Brain Capillaries, Gopal V. Velmurugan, Hemendra J. Vekaria, Anika M. S. Hartz, Björn Bauer, William Brad Hubbard

Markey Cancer Center Faculty Publications

Background

Neurovascular deficits and blood-brain barrier (BBB) dysfunction are major hallmarks of brain trauma and neurodegenerative diseases. Oxidative stress is a prominent contributor to neurovascular unit (NVU) dysfunction and can propagate BBB disruption. Oxidative damage results in an imbalance of mitochondrial homeostasis, which can further drive functional impairment of brain capillaries. To this end, we developed a method to track mitochondrial-related changes after oxidative stress in the context of neurovascular pathophysiology as a critical endophenotype of neurodegenerative diseases.

Methods

To study brain capillary-specific mitochondrial function and dynamics in response to oxidative stress, we developed an ex vivo model in which …