Mitochondrial dynamics is a complex process, which involves the fission and fusion of mitochondrial outer and inner membranes. These processes organize the mitochondrial size and morphology, as well as their localization throughout the cells. In the last two decades, it has become a spotlight due to their importance in the pathophysiological processes, particularly in neurological diseases. It is known that Drp1, mitofusin 1 and 2, and Opa1 constitute the core of proteins that coordinate this intricate and dynamic process. Likewise, changes in the levels of reactive oxygen species (ROS) lead to modifications in the expression and/or activity of the proteins implicated in the mitochondrial dynamics, suggesting an involvement of these molecules in the process. In this review, we discuss the role of ROS in the regulation of fusion/fission in the nervous system, as well as the involvement of mitochondrial dynamics proteins in neurodegenerative diseases.

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Background During excitotoxic damage, neuronal death results from the increase in intracellular calcium, the induction of oxidative stress, and a subsequent inflammatory response. NADPH oxidases (NOX) are relevant sources of reactive oxygen species (ROS) during excitotoxic damage. NADPH oxidase-2 (NOX-2) has been particularly related to neuronal damage and death, as well as to the resolution of the subsequent inflammatory response. As ROS are crucial components of the regulation of inflammatory response, in this work, we evaluated the role of NOX-2 in the progression of inflammation resulting from glutamate-induced excitotoxic damage of the striatum in an in vivo model. Methods The striata of wild-type C57BL/6 J and NOX-2 KO mice (gp91 Cybbtm1Din/J ) were stereotactically injected with monosodium glutamate either alone or in combination with IL-4 or IL-10. The damage was evaluated in histological sections stained with cresyl violet and Fluoro-Jade B. The enzymatic activity of caspase-3 and NOX were also measured. Additionally, the cytokine profile was identified by ELISA and motor activity was verified by the tests of the cylinder, the adhesive tape removal, and the inverted grid. Results Our results show a neuroprotective effect in mice with a genetic inhibition of NOX-2, which is partially due to a differential response to excitotoxic damage, characterized by the production of anti-inflammatory cytokines. In NOX-2 KO animals, the excitotoxic condition increased the production of interleukin-4, which could contribute to the production of interleukin-10 that decreased neuronal apoptotic death and the magnitude of striatal injury. Treatment with interleukin-4 and interleukin-10 protected from excitotoxic damage in wild-type animals. Conclusions The release of proinflammatory cytokines during the excitotoxic event promotes an additional apoptotic death of neurons that survived the initial damage. During the subsequent inflammatory response to excitotoxic damage, ROS generated by NOX-2 play a decisive role in the extension of the lesion and consequently in the severity of the functional compromise, probably by regulating the anti-inflammatory cytokines production. Electronic supplementary material The online version of this article (10.1186/s12974-019-1478-4) contains supplementary material, which is available to authorized users.

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Regeneration of ethanol-injured rat gastric mucosa must undergo changes in major metabolic pathways to achieve DNA replication and cell proliferation. These events are highly dependent on glucose utilization and inhibited by vitamin E (VE) (α-tocopherol) administration. Therefore, the present study aimed at assessing lipid metabolism in the gastric mucosa and ethanol-induced gastric damage and the effect of α-tocopherol administration. For this, rates of fatty acid β-oxidation and lipogenesis were tested in gastric mucosa samples. Through histological analysis, we found loss of the mucosa's superficial epithelium, which became gradually normalized during the recovery period. Proliferation of gastric mucosa occurred with augmented formation of β-oxidation by-products, diminished synthesis of triacylglycerols (TGs), as well as of phospholipids, and a reduced cytoplasmic NAD/NADH ratio, whereas the mitochondrial redox NAD/NADH ratio was much less affected. In addition, α-tocopherol increased palmitic acid utilization in the gastric mucosa, which was accompanied by the induction of 'mirror image' effects on the cell redox state, reflected in an inhibited cell gastric mucosa proliferation by the vitamin administration. In conclusion, the present study shows, for the first time, the role of lipid metabolism in the adaptive cell gastric mucosa changes that drive proliferation after a chronic insult. Moreover, α-tocopherol increased gastric mucosa utilization of palmitic acid associated with energy production. These events could be associated with its antioxidant properties in co-ordination with regulation of genes and cell pathways, including changes in the cell NAD/NADH redox state.