In vivo hydrogen peroxide diffusivity in brain tissue supports volume signaling activity
Hydrogen peroxide is a major redox signaling molecule underlying a novel paradigm of cell function and communication. A role for H2O2 as an intercellular signaling molecule and neuromodulator in the brain has become increasingly apparent, with evidence showing this biological oxidant to regulate neu...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-04-01
|
| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231722000222 |
| _version_ | 1818331952174858240 |
|---|---|
| author | A. Ledo E. Fernandes A. Salvador J. Laranjinha R.M. Barbosa |
| author_facet | A. Ledo E. Fernandes A. Salvador J. Laranjinha R.M. Barbosa |
| author_sort | A. Ledo |
| collection | DOAJ |
| description | Hydrogen peroxide is a major redox signaling molecule underlying a novel paradigm of cell function and communication. A role for H2O2 as an intercellular signaling molecule and neuromodulator in the brain has become increasingly apparent, with evidence showing this biological oxidant to regulate neuronal polarity, connectivity, synaptic transmission and tuning of neuronal networks. This notion is supported by its ability to diffuse in the extracellular space, from source of production to target. It is, thus, crucial to understand extracellular H2O2 concentration dynamics in the living brain and the factors which shape its diffusion pattern and half-life. To address this issue, we have used a novel microsensor to measure H2O2 concentration dynamics in the brain extracellular matrix both in an ex vivo model using rodent brain slices and in vivo. We found that exogenously applied H2O2 is removed from the extracellular space with an average half-life of t1/2 = 2.2 s in vivo. We determined the in vivo effective diffusion coefficient of H2O2 to be D* = 2.5 × 10−5 cm2 s−1. This allows it to diffuse over 100 μm in the extracellular space within its half-life. Considering this, we can tentatively place H2O2 within the class of volume neurotransmitters, connecting all cell types within the complex network of brain tissue, regardless of whether they are physically connected. These quantitative details of H2O2 diffusion and half-life in the brain allow us to interpret the physiology of the redox signal and lay the pavement to then address dysregulation in redox homeostasis associated with disease processes. |
| first_indexed | 2024-12-13T13:28:01Z |
| format | Article |
| id | doaj.art-d76b756af9294c4fbab19d44268b9ba7 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-13T13:28:01Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-d76b756af9294c4fbab19d44268b9ba72022-12-21T23:44:14ZengElsevierRedox Biology2213-23172022-04-0150102250In vivo hydrogen peroxide diffusivity in brain tissue supports volume signaling activityA. Ledo0E. Fernandes1A. Salvador2J. Laranjinha3R.M. Barbosa4Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504, Coimbra, Portugal; Corresponding author. Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal.Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548, Coimbra, PortugalCenter for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Casa Costa Alemão, 3030-789, Coimbra, Portugal; CQC, Department of Chemistry, University of Coimbra, Rua Larga, 3000-535, Coimbra, PortugalFaculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504, Coimbra, PortugalFaculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504, Coimbra, PortugalHydrogen peroxide is a major redox signaling molecule underlying a novel paradigm of cell function and communication. A role for H2O2 as an intercellular signaling molecule and neuromodulator in the brain has become increasingly apparent, with evidence showing this biological oxidant to regulate neuronal polarity, connectivity, synaptic transmission and tuning of neuronal networks. This notion is supported by its ability to diffuse in the extracellular space, from source of production to target. It is, thus, crucial to understand extracellular H2O2 concentration dynamics in the living brain and the factors which shape its diffusion pattern and half-life. To address this issue, we have used a novel microsensor to measure H2O2 concentration dynamics in the brain extracellular matrix both in an ex vivo model using rodent brain slices and in vivo. We found that exogenously applied H2O2 is removed from the extracellular space with an average half-life of t1/2 = 2.2 s in vivo. We determined the in vivo effective diffusion coefficient of H2O2 to be D* = 2.5 × 10−5 cm2 s−1. This allows it to diffuse over 100 μm in the extracellular space within its half-life. Considering this, we can tentatively place H2O2 within the class of volume neurotransmitters, connecting all cell types within the complex network of brain tissue, regardless of whether they are physically connected. These quantitative details of H2O2 diffusion and half-life in the brain allow us to interpret the physiology of the redox signal and lay the pavement to then address dysregulation in redox homeostasis associated with disease processes.http://www.sciencedirect.com/science/article/pii/S2213231722000222Hydrogen peroxideVolume signalingDiffusionBrain |
| spellingShingle | A. Ledo E. Fernandes A. Salvador J. Laranjinha R.M. Barbosa In vivo hydrogen peroxide diffusivity in brain tissue supports volume signaling activity Redox Biology Hydrogen peroxide Volume signaling Diffusion Brain |
| title | In vivo hydrogen peroxide diffusivity in brain tissue supports volume signaling activity |
| title_full | In vivo hydrogen peroxide diffusivity in brain tissue supports volume signaling activity |
| title_fullStr | In vivo hydrogen peroxide diffusivity in brain tissue supports volume signaling activity |
| title_full_unstemmed | In vivo hydrogen peroxide diffusivity in brain tissue supports volume signaling activity |
| title_short | In vivo hydrogen peroxide diffusivity in brain tissue supports volume signaling activity |
| title_sort | in vivo hydrogen peroxide diffusivity in brain tissue supports volume signaling activity |
| topic | Hydrogen peroxide Volume signaling Diffusion Brain |
| url | http://www.sciencedirect.com/science/article/pii/S2213231722000222 |
| work_keys_str_mv | AT aledo invivohydrogenperoxidediffusivityinbraintissuesupportsvolumesignalingactivity AT efernandes invivohydrogenperoxidediffusivityinbraintissuesupportsvolumesignalingactivity AT asalvador invivohydrogenperoxidediffusivityinbraintissuesupportsvolumesignalingactivity AT jlaranjinha invivohydrogenperoxidediffusivityinbraintissuesupportsvolumesignalingactivity AT rmbarbosa invivohydrogenperoxidediffusivityinbraintissuesupportsvolumesignalingactivity |