Modeling mitochondrial dysfunctions in the brain: from mice to men

Abstract

The biologist Lewis Thomas once wrote: “my mitochondria comprise a very large proportion of me. I cannot do the calculation, but I suppose there is almost as much of them in sheer dry bulk as there is the rest of me”. As humans, or indeed as any mammal, bird, or insect, we contain a specific molecular makeup that is driven by vast numbers of these miniscule powerhouses residing in most of our cells (mature red blood cells notwithstanding), quietly replicating, living independent lives and containing their own DNA. Everything we do, from running a marathon to breathing, is driven by these small batteries, and yet there is evidence that these molecular energy sources were originally bacteria, possibly parasitic, incorporated into our cells through symbiosis. Dysfunctions in these organelles can lead to debilitating, and sometimes fatal, diseases of almost all the bodies’ major organs. Mitochondrial dysfunction has been implicated in a wide variety of human disorders either as a primary cause or as a secondary consequence. To better understand the role of mitochondrial dysfunction in human disease, a multitude of pharmacologically induced and genetically manipulated animal models have been developed showing to a greater or lesser extent the clinical symptoms observed in patients with known and unknown causes of the disease. This review will focus on diseases of the brain and spinal cord in which mitochondrial dysfunction has been proven or is suspected and on animal models that are currently used to study the etiology, pathogenesis and treatment of these diseases.

3-n-Butylphthalide reduces the oxidative damage of muscles in an experimental autoimmune myositis animal model

“…Mitochondrial disorder manifests as a pathology of IIMs and may provide evidence for the underlying pathogenic mechanisms ( 6 ). The mitochondria are essential organelles that are indispensable for normal cell processes, such as cell proliferation and programmed cell death ( 7 ). Mitochondrial respiration not only generates cellular energy, but is also the main source of reactive oxygen species (ROS) in most tissues ( 8 ).…”

Cellular and animal models for mitochondrial complex I deficiency: A focus on the NDUFS4 subunit

“…NesKO mice display neuronal damage in brain areas associated with movement, including the cerebellum, striatum, and basal ganglia (41), while Ndufs4-PC mice show enhanced neuronal damage in the PCs of the cerebellum. However, Ndufs4-PC mice only show mild behavioral and neuropathological abnormalities, compared to the WBKO mouse (42).…”

Effect of Exercise on Oxidative Stress in Neurological Disorders

“…Neuronal oxidative stress and mitochondrial dysfunction are closely associated with the pathogenesis of normal aging, neurotraumatic, neurodegenerative, and neuropsychiatric diseases (Farooqui 2010;Breuer et al 2012). As stated above, regular exercise has a positive impact on cognition and brain function.…”