Environmental changes in oxygen tension reveal ROS-dependent neurogenesis and regeneration in the adult newt brain

Abstract

Organisms need to adapt to the ecological constraints in their habitat. How specific processes reflect such adaptations are difficult to model experimentally. We tested whether environmental shifts in oxygen tension lead to events in the adult newt brain that share features with processes occurring during neuronal regeneration under normoxia. By experimental simulation of varying oxygen concentrations, we show that hypoxia followed by re-oxygenation lead to neuronal death and hallmarks of an injury response, including activation of neural stem cells ultimately leading to neurogenesis. Neural stem cells accumulate reactive oxygen species (ROS) during re-oxygenation and inhibition of ROS biosynthesis counteracts their proliferation as well as neurogenesis. Importantly, regeneration of dopamine neurons under normoxia also depends on ROS-production. These data demonstrate a role for ROS-production in neurogenesis in newts and suggest that this role may have been recruited to the capacity to replace lost neurons in the brain of an adult vertebrate.DOI: http://dx.doi.org/10.7554/eLife.08422.001

Amputation‐induced reactive oxygen species signaling is required for axolotl tail regeneration

“…Urodele amphibians are exceptional in regards to regenerating complex organs and tissues. Our results are consistent with findings from studies of planaria (Pirotte et al, ), zebrafish fin (Gauron et al, 2013), Xenopus tail (Love et al, ), and newt adult brain (Hameed et al, ); clearly ROS are required for successful tissue / appendage regeneration . We show that ROS are produced shortly after amputation in axial tissues and their production is sustained during the first 24 hpa.…”

“…ROS are well‐known components of metazoan innate immune responses and, at moderate concentrations, serve others roles in tissue injury, wound healing, cellular signaling, and gene expression (Weidinger and Kozlov, ). A growing number of studies highlight ROS in the regeneration of organs that span vertebrate and invertebrate taxa, thus implicating ROS as a phylogenetically conserved mechanism that initiates regeneration programs (Niethammer et al, ; Gauron et al, ; Love et al, ; Piorette et al, 2015; Hameed et al, ; Zhang et al, ). These and other studies (Yoo et al, ; Lisse et al, ) show that ROS recruit regeneration‐permissive lymphocytes, induce mitogen signaling pathways required for progenitor cell proliferation, and modulate cell fate.…”

Redox regulation in regenerative medicine and tissue engineering: The paradox of oxygen

“…Apart from its role as an important redox sensor protein involved in stimulating anaerobic metabolism, angiogenesis, and enhancing endogenous antioxidant systems (Stegen, van Gastel, et al, ; Thirlwell et al, ), HIF is also an important regulator in the regeneration of different tissues including neurons, heart, bone, cartilage, and pancreas. In neurons, low oxygen tension induces ROS, which is a signal for neurogenesis (Hameed et al, ; Zeng, Kamei, Wang, & Tsai, ), and HIF1α signalling enhances axon regeneration (Alam et al, ; Cho et al, ), which is also linked to ROS levels (Quinta et al, ). In the heart, Hif1α is essential for cardiomyogenesis (Kudova et al, ), and the hypoxia experienced after myocardial infarction is known to enhance the systolic function of the left ventricle and prevent fibrosis in mice (Nakada et al, ).…”

Concise Review: Translating Regenerative Biology into Clinically Relevant Therapies: Are We on the Right Path?

“…Prior to blastema formation, cellular interactions with the immune environment partially determine if a blastema will form [18,20,21,29,[99][100][101]. In adult tissues, the immediate response to injury includes the infiltration of a diverse subset of leukocytes including neutrophils, macrophages, and T cells.…”