Free radicals attack. These are  uncharged, highly reactive, molecules having an unpaired valence electron. In neurodegenerative pathology free radicals come from  over-reactive defenders (microglial cells) and damaged power stations (mitochondria), mostly.

There is no organ as sensitive as the brain to changes in energetic metabolism. It consumes 20% of all the O2 when a person is at rest, and 25% of total body glucose utilization. This consumption is 10 times the rate of the rest of the body per gram of tissue. Taking into account a consumption of 2400 kcal/24 hours for a typical adult, it means 100 Kcal/hour or 116.38 J/s in terms of energy. 20% of 116.38 J/s is 23.3 J/s or Watts, if expressed in terms of power. Because most neuronal energy is generated by oxidative metabolism, neurons critically depend on mitochondrial function, which explains the interconnection between neuronal activity and mitochondrial metabolic activity, and oxygen supply. The latter explains why oxygen consumption in the brain is 160 mmol/100 g·min, and why it consumes glucose at a rate of 31 μmol/100 g·min.19 An estimated 1–4% of the oxygen taken into cells, however, is prematurely and incompletely reduced, giving rise to reactive oxygen species (ROS).17 A major source of oxidants, as a consequence of electron leakage, comes from mitochondria. In fact, mitochondrial dysfunction and associated oxidant stress have been linked to numerous complex diseases and aging. Oxidative stress produces membrane alterations particularly associated with lipid modifications.20

If you want to visualize what a free radical is, just think  about this: a potato in flames going from hand to hand in a nice ordered crowd of people doing his job. Everything become a mess.

In damaged mitochondrial membranes, the leak of electrons becomes predictable, feeding back to produce ROS and oxidative stress. In fact, Aβ-induced oxidative stress provokes significant alterations in cholesterol and fatty acids (their composition, disposition, and distribution) in mitochondrial membranes, as observed in vivo.21 This is particularly significant because lipids may allow, facilitate, or even induce the amyloidogenic processing of the amyloid precursor protein. Oxidative stress is thus linked to cellular membrane dysfunction. This phenomenon is due to damage to membrane lipids, which are among the most vulnerable cellular components to oxidative stress. It is well known that the brain has the highest concentration of fatty acids of any organ. The lipid content in brain white matter may reach 66%, 40% in gray matter, and more than 80% in isolated myelin from white matter.22

By studying neurobehavioral deficits and brain oxidative stress induced by chronic low dose exposure of persistent organic pollutants mixture in adult female rat, Persistent organic pollutants (POPs) (long-lived organic compounds that are considered one of the major risks to ecosystem and human health) like endosulfan (2.6 μg/kg), chlorpyrifos (5.2 μg/kg), naphthalene (0.023 μg/kg) and benzopyrane (0.002 μg/kg) has been tested. Exposed rats have shown a disturbance of memory and a decrease in learning ability concluded by Morris water maze and the open field tests results and anxiolytic behaviour in the test of light/dark box compared to control. Concerning brain redox homeostasis, exposed rats have shown an increased malondialdehyde (MDA) amount and an alteration in glutathione (GSH) levels in both the brain mitochondria and cytosolic fractions of the cerebellum, striatum and hippocampus. These effects were accompanied by a decrease in levels of cytosolic glutathione S-transferase (GST) and a highly significant increase in superoxide dismutase (SOD) and catalase (CAT) activities in both cytosolic and mitochondrial fractions. The current study suggests that environmental exposure to daily even low doses of POPs mixtures through diet induces oxidative stress status in the brain and especially in the mitochondria with important cognitive and locomotor behaviour variations in the rats.

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