Optical and pharmacological tools to investigate the role of mitochondria during oxidative stress and neurodegeneration

Abstract

Mitochondria are critical for cellular ATP production; however, recent studies suggest that these organelles fulfill a much broader range of tasks. For example, they are involved in the regulation of cytosolic Ca 2+ levels, intracellular pH and apoptosis, and are the major source of reactive oxygen species (ROS). Various reactive molecules that originate from mitochondria, such as ROS, are critical in pathological events, such as ischemia, as well as in physiological events such as long-term potentiation, neuronal-vascular coupling and neuronal-glial interactions. Due to their key roles in the regulation of several cellular functions, the dysfunction of mitochondria may be critical in various brain disorders. There has been increasing interest in the development of tools that modulate mitochondrial function, and the refinement of techniques that allow for real time monitoring of mitochondria, particularly within their intact cellular environment. Innovative imaging techniques are especially powerful since they allow for mitochondrial visualization at high resolution, tracking of mitochondrial structures and optical real time monitoring of parameters of mitochondrial function. Among the techniques discussed are the uses of classic imaging techniques such as rhodamine-123, the highly advanced semi-conductor nanoparticles (quantum dots), and wide field microscopy as well as high-resolution multi-photon imaging. We have highlighted the use of these techniques to study mitochondrial function in brain tissue and have included studies from our laboratories in which these techniques have been successfully applied.

Oxidative stress-mediated antibacterial activity of graphene oxide and reduced graphene oxide in Pseudomonas aeruginosa

“…59,60 ROS typically include the superoxide radical (O 2− ), hydrogen peroxide (H 2 O 2 ), and hydroxyl radical (OH), which cause damage to cellular components, including DNA and proteins. 61,62 ROS generation is also an important factor in the apoptosis process, and the excess generation of ROS induces mitochondrial membrane permeability and damages the respiratory chain to trigger the apoptotic process. 63,64 Specific DNA smearing is a characteristic feature of cell death.…”

Oxidative Stress and Neurodegenerative Disease

“…In addition they maintain the intracellular levels of calcium within appropriate ranges to mediate cell signaling and control neuronal excitability and synaptic function. In the brain there is a metabolic coupling between vascular substrates, providing oxygen and glucose and the metabolic needs of the brain tissue, formed by neurons and glia alike (Foster et al, 2006).The sequence of events that occurs after neural stimulation includes an initial decrease of oxygen in areas of high demand for this gas (for example, those first stimulated) and a large further increase of oxygen associated with a wide field of arterial vasodilatation. These events are closely related to mitochondrial activity through the production of H 2 O 2 as a signaling molecule (Foster et al, 2006).…”

“…In the brain there is a metabolic coupling between vascular substrates, providing oxygen and glucose and the metabolic needs of the brain tissue, formed by neurons and glia alike (Foster et al, 2006).The sequence of events that occurs after neural stimulation includes an initial decrease of oxygen in areas of high demand for this gas (for example, those first stimulated) and a large further increase of oxygen associated with a wide field of arterial vasodilatation. These events are closely related to mitochondrial activity through the production of H 2 O 2 as a signaling molecule (Foster et al, 2006). Like other cells, nerve cells use ATP as a source of energy for biochemical processes involved in various cell functions, and produce ROS as a result of oxidative phosphorylation.…”

Effects of relative hypoglycemia on LTP and NADH imaging in rat hippocampal slices

“…These changes show, in real time, significant reductions in the available energy pool within cells. This method also has the advantage of being non-invasive, in contrast with most studies directly measuring ATP, which use rapid freezing, homogenization and subsequent optical quantification [13], and thus require destruction of the tissue.…”