Induction of Oxidative Stress and Apoptosis in the Injured Brain: Potential Relevance to Brain Regeneration in Zebrafish.

Abstract

In the recent years, zebrafish, owing to its tremendous adult neurogenic capacity, has emerged as a useful vertebrate model to study brain regeneration. Recent findings suggest a significant role of the BDNF/TrkB signaling as a mediator of brain regeneration following a stab injury in the adult zebrafish brain. Since BDNF has been implicated in a plethora of physiological processes, we hypothesized that these processes are affected in the injured zebrafish brain. In this small study, we examined the indicators of oxidative stress and of apoptosis using biochemical assays, RT-PCR and IHC to reflect upon the impact of stab injury on oxidative stress levels and apoptosis in the injured adult zebafish brain. Our results indicate induction of oxidative stress in the injured adult zebrafish brain. Also, apoptosis was induced in the injured brain as indicated by increased protein levels of cleaved caspase3 as well as enhanced mRNA levels of both pro-apoptotic and anti-apoptotic genes. This knowledge contributes to the overall understanding of adult neurogenesis in the zebrafish model and raises new questions pertaining to the compensatory physiological mechanisms in response to traumatic brain injury in the adult zebrafish brain.

Distribution of microglia/immune cells in the brain of adult zebrafish in homeostatic and regenerative conditions: Focus on oxidative stress during brain repair

“…These last results are in agreement with the recent study by Anand et al. (2021) showing that stab wounding of the zebrafish telencephalon leads to a significant increase in SOD activity at 1 and 4 dpl, correlated with a significant increase in lipid peroxidation and reduced levels of glutathione (GSH). Interestingly, we showed the significant upregulation of the glutathione reductase gene.…”

“…This was confirmed by the increase in H 2 O 2 levels revealed by the Amplex Red assay and by the increased SOD activity, an antioxidant enzyme known to be upregulated under pro-oxidative conditions. These last results are in agreement with the recent study by Anand et al (2021) showing that stab wounding of the zebrafish telencephalon leads to a significant increase in SOD activity at 1 and 4 dpl, correlated with a significant increase in lipid peroxidation and reduced levels of glutathione (GSH). Interestingly, we showed the significant upregulation of the glutathione reductase gene.…”

“…Indeed, glutathione reductase catalyzes the reduction of glutathione disulfide (GSSG, the oxidized form of glutathione) to glutathione in the sulfhydryl form (GSH, the reduced form), participating in the resistance to oxidative stress and the maintenance of a reducing environment. Thus, the work of Anand et al (2021) and ours suggest that the expression of the glutathione reductase enzyme is increased during brain repair and leads to higher amount of GSH (glutathione) that is an antioxidant species preventing cell damage caused by ROS (Pompella et al, 2003).…”

“…While the characterization of antioxidant defenses is well described in mammals during injury (Lin et al, 2021;Praveen Kumar et al, 2021), very few data are available in zebrafish. Nevertheless, the recent work from Anand et al (2021) demonstrated that antioxidant enzyme activity was modulated after zebrafish brain injury in links with increased levels of lipid peroxidation and GSH (reduced glutathione).…”

“…Nevertheless, the recent work from Anand et al. (2021) demonstrated that antioxidant enzyme activity was modulated after zebrafish brain injury in links with increased levels of lipid peroxidation and GSH (reduced glutathione).…”