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

Hameed LS, Berg DA, Belnoue L, Jensen LD, Cao Y, Simon A - Elife (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.

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.

No MeSH data available.


Related in: MedlinePlus

Apocynin does not inhibit microglia proliferation in vivo but abrogates neurosphere-formation after hypoxia/re-oxygenation.(A) The number of proliferating microglia cells assessed by PCNA+/IBA1+ cells is not affected by apocynin treatment. n = 4. (Unpaired t-test). (B) Apocynin does not inhibit neurosphere formation in normoxic conditions. n = 4. (Unpaired t-test). (C) Apocynin abrogates hypoxia/re-oxygenation-induced increase in neurosphere formation. n = 6, *p < 0.05 (Unpaired t-test).DOI:http://dx.doi.org/10.7554/eLife.08422.017
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fig4s1: Apocynin does not inhibit microglia proliferation in vivo but abrogates neurosphere-formation after hypoxia/re-oxygenation.(A) The number of proliferating microglia cells assessed by PCNA+/IBA1+ cells is not affected by apocynin treatment. n = 4. (Unpaired t-test). (B) Apocynin does not inhibit neurosphere formation in normoxic conditions. n = 4. (Unpaired t-test). (C) Apocynin abrogates hypoxia/re-oxygenation-induced increase in neurosphere formation. n = 6, *p < 0.05 (Unpaired t-test).DOI:http://dx.doi.org/10.7554/eLife.08422.017

Mentions: Previous studies in zebrafish have demonstrated a critical role of inflammatory cells, such as microglia, in NSC activation following traumatic brain injury (Kyritsis et al., 2012). We next addressed whether microglia activation plays an important role in ependymoglia cell proliferation following hypoxia/re-oxygenation in the newt. To suppress microglia activation, we administered dexamethasone to animals twice daily for 5 days prior to shifting them to hypoxia and twice daily for three days post re-oxygenation. In accordance with previous reports (Kirkham et al., 2011; Kyritsis et al., 2012), the number of proliferating microglial cells was reduced 3.8-fold compared to vehicle-injected animals (Figure 4A,B). In contrast, the proliferative response by ependymoglia cells to hypoxia/re-oxygenation was not altered (Figure 4C,D). Consistently, we did not observe any significant decrease of microglia activation in apocynin-treated animals compared to the controls (Figure 4—figure supplement 1A). These results indicated that activation of ependymoglia cells was independent of microglia activation following hypoxia/re-oxygenation.10.7554/eLife.08422.014Figure 4.Suppression of microglia activation does not inhibit hypoxia/re-oxygenation–induced ependymoglia proliferation.


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

Hameed LS, Berg DA, Belnoue L, Jensen LD, Cao Y, Simon A - Elife (2015)

Apocynin does not inhibit microglia proliferation in vivo but abrogates neurosphere-formation after hypoxia/re-oxygenation.(A) The number of proliferating microglia cells assessed by PCNA+/IBA1+ cells is not affected by apocynin treatment. n = 4. (Unpaired t-test). (B) Apocynin does not inhibit neurosphere formation in normoxic conditions. n = 4. (Unpaired t-test). (C) Apocynin abrogates hypoxia/re-oxygenation-induced increase in neurosphere formation. n = 6, *p < 0.05 (Unpaired t-test).DOI:http://dx.doi.org/10.7554/eLife.08422.017
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getmorefigures.php?uid=PMC4635398&req=5

fig4s1: Apocynin does not inhibit microglia proliferation in vivo but abrogates neurosphere-formation after hypoxia/re-oxygenation.(A) The number of proliferating microglia cells assessed by PCNA+/IBA1+ cells is not affected by apocynin treatment. n = 4. (Unpaired t-test). (B) Apocynin does not inhibit neurosphere formation in normoxic conditions. n = 4. (Unpaired t-test). (C) Apocynin abrogates hypoxia/re-oxygenation-induced increase in neurosphere formation. n = 6, *p < 0.05 (Unpaired t-test).DOI:http://dx.doi.org/10.7554/eLife.08422.017
Mentions: Previous studies in zebrafish have demonstrated a critical role of inflammatory cells, such as microglia, in NSC activation following traumatic brain injury (Kyritsis et al., 2012). We next addressed whether microglia activation plays an important role in ependymoglia cell proliferation following hypoxia/re-oxygenation in the newt. To suppress microglia activation, we administered dexamethasone to animals twice daily for 5 days prior to shifting them to hypoxia and twice daily for three days post re-oxygenation. In accordance with previous reports (Kirkham et al., 2011; Kyritsis et al., 2012), the number of proliferating microglial cells was reduced 3.8-fold compared to vehicle-injected animals (Figure 4A,B). In contrast, the proliferative response by ependymoglia cells to hypoxia/re-oxygenation was not altered (Figure 4C,D). Consistently, we did not observe any significant decrease of microglia activation in apocynin-treated animals compared to the controls (Figure 4—figure supplement 1A). These results indicated that activation of ependymoglia cells was independent of microglia activation following hypoxia/re-oxygenation.10.7554/eLife.08422.014Figure 4.Suppression of microglia activation does not inhibit hypoxia/re-oxygenation–induced ependymoglia proliferation.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.

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.

No MeSH data available.


Related in: MedlinePlus