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Updated: Apr 17, 2026
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Generation and On-Demand Initiation of Acute Ictal Activity in Rodent and Human Tissue
Published on: January 19, 2019
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In vivo chemogenetic generation of intraneuronal H2O2
Dmitry I Maltsev1, Maxim A Solotenkov2, Ekaterina A Elesina3
1Pirogov Russian National Research Medical University, 117997, Moscow, Russia; Federal Center of Brain Research and Neurotechnologies, Federal Medical Biological Agency, 117997, Moscow, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia.
Free Radical Biology & Medicine
|January 7, 2026
Summary
Researchers developed a new method using D-amino acid oxidase (DAAO) to induce oxidative stress in the brain. This chemogenetic approach successfully generated hydrogen peroxide (H2O2) in vivo, offering a tool for studying neurodegenerative diseases.
Area of Science:
- Neuroscience
- Biochemistry
- Molecular Biology
Background:
- Recombinant D-amino acid oxidase (DAAO) is a chemogenetic tool for controlled intracellular hydrogen peroxide (H2O2) generation.
- Oxidative stress is implicated in aging-related degenerative disorders.
- Inducing oxidative stress in the brain in vivo using this tool remained untested.
Purpose of the Study:
- To test the feasibility of using DAAO for chemogenetic induction of oxidative stress in the brain in vivo.
- To examine the real-time production of H2O2 in hippocampal neurons.
Main Methods:
- Viral vector-mediated expression of DAAO and the H2O2 biosensor HyPer7 in hippocampal neurons.
- Real-time in vivo fiber photometry.
- Delivery of D-norvaline via intraperitoneal injections or drinking water.
- Raman microspectroscopy to assess mitochondrial function.
Main Results:
- Confirmed controlled intraneuronal H2O2 generation in vivo using DAAO and D-norvaline via both administration routes.
- Observed changes in HyPer7 signal indicated successful H2O2 production.
- Raman microspectroscopy showed reduced electron transport chain loading.
Conclusions:
- The DAAO-based chemogenetic tool is suitable for inducing chronic oxidative stress in the brain in vivo.
- D-norvaline delivery via intraperitoneal injection or drinking water effectively enables this induction.
- This method provides a valuable approach for studying oxidative stress in neurological disorders.
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