Component

Mouse D-aspartate oxidase / Ddo

Context-specific entity; species, compartment and exposure are stated on each claim.

10 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. Persistent D-aspartate elevation after Ddo deletion accompanied increased extracellular glutamate, active caspases, reactive glia and age-dependent brain abnormalities.

    Mouse D-aspartate oxidase / Ddo → Age-dependent brain pathology after mouse Ddo deletion source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Constitutive Ddo-knockout mice studied across age.
    limitations
    Genetic lifelong exposure is not equivalent to a short human supplement course.
    nutrient_topic
    D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate
    plain_language
    Long-term loss of clearance had adverse outcomes despite some short-term signaling effects.
    primary_references
    d-Aspartate oxidase influences glutamatergic system homeostasis in mammalian brain. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25771393/ · DOI 10.1016/j.neurobiolaging.2015.02.003
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 248–254

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Constitutive Ddo-knockout mice studied across age. · source_derived_draft · unverified_draft

    ## d-aspartate-chronic-loss-aging Long-term loss of clearance had adverse outcomes despite some short-term signaling effects. Persistent D-aspartate elevation after Ddo deletion accompanied increased extracellular glutamate, active caspases, reactive glia and age-dependent brain abnormalities. Model: Constitutive Ddo-knockout mice studied across age. Limitations: Genetic lifelong exposure is not equivalent to a short human supplement course. Evidence access: Primary abstract d-Aspartate oxidase influences glutamatergic system homeostasis in mammalian brain. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25771393/ · DOI 10.1016/j.neurobiolaging.2015.02.003
    Complete structured claim and evidence

  2. Aged Ddo-knockout mice showed reduced synaptic GluN1/GluN2B, altered plasticity and greater vulnerability to phencyclidine-related prepulse-inhibition deficits.

    Mouse D-aspartate oxidase / Ddo → Synaptic NMDA receptor availability in mouse hippocampus source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Aging Ddo-knockout mouse hippocampus and behavior.
    limitations
    Different age/region/endpoint from nigral GluN1/GluN2A increases; recorded as context, not a wording correction.
    nutrient_topic
    D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate
    plain_language
    Receptor adaptation can reverse the apparent direction of an earlier signaling effect.
    primary_references
    d-Aspartate oxidase influences glutamatergic system homeostasis in mammalian brain. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25771393/ · DOI 10.1016/j.neurobiolaging.2015.02.003
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 256–262

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Aging Ddo-knockout mouse hippocampus and behavior. · source_derived_draft · unverified_draft

    ## d-aspartate-chronic-loss-receptors Receptor adaptation can reverse the apparent direction of an earlier signaling effect. Aged Ddo-knockout mice showed reduced synaptic GluN1/GluN2B, altered plasticity and greater vulnerability to phencyclidine-related prepulse-inhibition deficits. Model: Aging Ddo-knockout mouse hippocampus and behavior. Limitations: Different age/region/endpoint from nigral GluN1/GluN2A increases; recorded as context, not a wording correction. Evidence access: Primary abstract d-Aspartate oxidase influences glutamatergic system homeostasis in mammalian brain. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25771393/ · DOI 10.1016/j.neurobiolaging.2015.02.003
    Complete structured claim and evidence

  3. Ddo deletion increased NMDA-evoked currents and membrane GluN1/GluN2A in mouse nigral dopamine neurons.

    Mouse D-aspartate oxidase / Ddo → Mouse NMDA-type receptors, subunits unresolved source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Ddo-knockout mouse substantia-nigra neurons.
    limitations
    Region-specific knockout response; not a universal change after oral supplementation.
    nutrient_topic
    D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate
    plain_language
    Prolonged higher D-aspartate was accompanied by receptor remodeling.
    primary_references
    Persistent elevation of D-Aspartate enhances NMDA receptor-mediated responses in mouse substantia nigra pars compacta dopamine neurons. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26707656/ · DOI 10.1016/j.neuropharm.2015.12.013
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 200–206

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Ddo-knockout mouse substantia-nigra neurons. · source_derived_draft · unverified_draft

    ## d-aspartate-ddo-loss-nmdar Prolonged higher D-aspartate was accompanied by receptor remodeling. Ddo deletion increased NMDA-evoked currents and membrane GluN1/GluN2A in mouse nigral dopamine neurons. Model: Ddo-knockout mouse substantia-nigra neurons. Limitations: Region-specific knockout response; not a universal change after oral supplementation. Evidence access: Primary abstract Persistent elevation of D-Aspartate enhances NMDA receptor-mediated responses in mouse substantia nigra pars compacta dopamine neurons. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26707656/ · DOI 10.1016/j.neuropharm.2015.12.013
    Complete structured claim and evidence

What acts on it

  1. Postnatal mouse Ddo promoter demethylation accompanied rising Ddo mRNA; azacitidine treatment increased Ddo transcripts in embryonic cortical neurons.

    Mouse Ddo promoter demethylation → Mouse D-aspartate oxidase / Ddo source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Mouse development and cultured embryonic-neuron demethylating-drug experiments.
    limitations
    Azacitidine has broad effects. This is not evidence that folate intake directly switches DDO on or off.
    nutrient_topic
    D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate
    plain_language
    Gene regulation can change the capacity to clear D-aspartate.
    primary_references
    Age-Related Changes in D-Aspartate Oxidase Promoter Methylation Control Extracellular D-Aspartate Levels and Prevent Precocious Cell Death during Brain Aging. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26961959/ · DOI 10.1523/JNEUROSCI.3881-15.2016

    D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 144–150

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse development and cultured embryonic-neuron demethylating-drug experiments. · source_derived_draft · unverified_draft

    ## d-aspartate-ddo-methylation Gene regulation can change the capacity to clear D-aspartate. Postnatal mouse Ddo promoter demethylation accompanied rising Ddo mRNA; azacitidine treatment increased Ddo transcripts in embryonic cortical neurons. Model: Mouse development and cultured embryonic-neuron demethylating-drug experiments. Limitations: Azacitidine has broad effects. This is not evidence that folate intake directly switches DDO on or off. Evidence access: Primary abstract Age-Related Changes in D-Aspartate Oxidase Promoter Methylation Control Extracellular D-Aspartate Levels and Prevent Precocious Cell Death during Brain Aging. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26961959/ · DOI 10.1523/JNEUROSCI.3881-15.2016
    Complete structured claim and evidence

  2. Purified human, rat and mouse DDO differed in kinetic and inhibitor-binding properties.

    Human D-aspartate oxidase / DDO → Mouse D-aspartate oxidase / Ddo source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Comparative recombinant enzyme assays and structural models.
    limitations
    Rodent efficacy is not a measured human effect.
    nutrient_topic
    D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate
    plain_language
    A compound that changes rodent clearance may act differently on the human enzyme.
    primary_references
    Characterization of the enzymatic and structural properties of human D-aspartate oxidase and comparison with those of the rat and mouse enzymes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25747990/ · DOI 10.1248/bpb.b14-00690

    D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 128–134

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Comparative recombinant enzyme assays and structural models. · source_derived_draft · unverified_draft

    ## d-aspartate-ddo-species A compound that changes rodent clearance may act differently on the human enzyme. Purified human, rat and mouse DDO differed in kinetic and inhibitor-binding properties. Model: Comparative recombinant enzyme assays and structural models. Limitations: Rodent efficacy is not a measured human effect. Evidence access: Primary abstract Characterization of the enzymatic and structural properties of human D-aspartate oxidase and comparison with those of the rat and mouse enzymes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25747990/ · DOI 10.1248/bpb.b14-00690
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Ddo deletion or oral D-aspartate elevation enhanced hippocampal LTP without improving cognitive flexibility in the reported mouse experiments.

    D-Aspartate → Mouse hippocampal long-term potentiation source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Mouse genetic and oral-exposure models; slices and behavioral tests.
    limitations
    LTP is not synonymous with better memory; oral dose not specified in accessed abstract.
    nutrient_topic
    D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate
    plain_language
    A stronger synaptic-plasticity signal did not translate into a general cognitive advantage.
    primary_references
    Increased levels of d-aspartate in the hippocampus enhance LTP but do not facilitate cognitive flexibility. · 2008 · https://pubmed.ncbi.nlm.nih.gov/17981050/ · DOI 10.1016/j.mcn.2007.09.012

    D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 240–246

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse genetic and oral-exposure models; slices and behavioral tests. · source_derived_draft · unverified_draft

    ## d-aspartate-ltp A stronger synaptic-plasticity signal did not translate into a general cognitive advantage. Ddo deletion or oral D-aspartate elevation enhanced hippocampal LTP without improving cognitive flexibility in the reported mouse experiments. Model: Mouse genetic and oral-exposure models; slices and behavioral tests. Limitations: LTP is not synonymous with better memory; oral dose not specified in accessed abstract. Evidence access: Primary abstract Increased levels of d-aspartate in the hippocampus enhance LTP but do not facilitate cognitive flexibility. · 2008 · https://pubmed.ncbi.nlm.nih.gov/17981050/ · DOI 10.1016/j.mcn.2007.09.012
    Complete structured claim and evidence

  2. Lowering assay FAD from 100 to 4 micromolar shifted olanzapine IC50 at mouse DDO from about 5.6 to 1.4 micromolar; the human enzyme did not show this potency shift.

    FAD → Olanzapine inhibition potency at mouse DDO source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Recombinant mouse versus human DDO assays.
    limitations
    This is not an observed dietary riboflavin-drug interaction in people.
    nutrient_topic
    D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate
    plain_language
    Cofactor conditions altered the mouse drug-enzyme interaction.
    primary_references
    Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28393897/ · DOI 10.1038/srep46288

    D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 272–278

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant mouse versus human DDO assays. · source_derived_draft · unverified_draft

    ## d-aspartate-olanzapine-fad-species Cofactor conditions altered the mouse drug-enzyme interaction. Lowering assay FAD from 100 to 4 micromolar shifted olanzapine IC50 at mouse DDO from about 5.6 to 1.4 micromolar; the human enzyme did not show this potency shift. Model: Recombinant mouse versus human DDO assays. Limitations: This is not an observed dietary riboflavin-drug interaction in people. Evidence access: Primary full text Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28393897/ · DOI 10.1038/srep46288
    Complete structured claim and evidence

  3. Four weeks of olanzapine at 5 mg/kg/day intraperitoneally increased prefrontal extracellular D-aspartate and glutamate in wild-type mice; the increments were absent in Ddo-knockout mice.

    Olanzapine → Extracellular D-aspartate in mouse prefrontal cortex source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Mouse microdialysis 24 hours after the final injection.
    limitations
    Knockouts already differ at baseline. This does not prove the pathway mediates clinical antipsychotic efficacy.
    nutrient_topic
    D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate
    plain_language
    Removing the enzyme removed this drug-associated increment in the mouse experiment.
    primary_references
    Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28393897/ · DOI 10.1038/srep46288

    D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 280–286

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse microdialysis 24 hours after the final injection. · source_derived_draft · unverified_draft

    ## d-aspartate-olanzapine-mouse-dependence Removing the enzyme removed this drug-associated increment in the mouse experiment. Four weeks of olanzapine at 5 mg/kg/day intraperitoneally increased prefrontal extracellular D-aspartate and glutamate in wild-type mice; the increments were absent in Ddo-knockout mice. Model: Mouse microdialysis 24 hours after the final injection. Limitations: Knockouts already differ at baseline. This does not prove the pathway mediates clinical antipsychotic efficacy. Evidence access: Primary full text Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28393897/ · DOI 10.1038/srep46288
    Complete structured claim and evidence

  4. Srr-knockout mouse forebrain had less D-aspartate without detected differences in DDO activity or L-aspartate concentrations.

    Mouse serine racemase / Srr → Mouse regional brain free D-aspartate pool source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Mouse frontal cortex, hippocampus and striatum; cerebellum unaffected.
    limitations
    Association supported a production hypothesis; it did not independently identify the complete biosynthetic pathway.
    nutrient_topic
    D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate
    plain_language
    A smaller pool was not explained by higher measured breakdown or lower L-aspartate.
    primary_references
    Decreased levels of free D-aspartic acid in the forebrain of serine racemase (Srr) knock-out mice. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23439386/ · DOI 10.1016/j.neuint.2013.02.015
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 48–54

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse frontal cortex, hippocampus and striatum; cerebellum unaffected. · source_derived_draft · unverified_draft

    ## d-aspartate-srr-loss-ddo-control A smaller pool was not explained by higher measured breakdown or lower L-aspartate. Srr-knockout mouse forebrain had less D-aspartate without detected differences in DDO activity or L-aspartate concentrations. Model: Mouse frontal cortex, hippocampus and striatum; cerebellum unaffected. Limitations: Association supported a production hypothesis; it did not independently identify the complete biosynthetic pathway. Evidence access: Primary abstract Decreased levels of free D-aspartic acid in the forebrain of serine racemase (Srr) knock-out mice. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23439386/ · DOI 10.1016/j.neuint.2013.02.015
    Complete structured claim and evidence

  5. EAAT inhibition strongly potentiated D-aspartate-evoked, but not L-aspartate-evoked, currents in Ddo-knockout mouse neurons.

    EAAT inhibition in mouse nigral neurons → Excitatory responses of mouse substantia-nigra dopamine neurons source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Ddo-knockout mouse nigral neuron transporter-blocker experiments.
    limitations
    A protective adaptation is an interpretation; human transporter failure and dietary consequences were not tested.
    nutrient_topic
    D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate
    plain_language
    Uptake can buffer excitation when breakdown is impaired.
    primary_references
    Persistent elevation of D-Aspartate enhances NMDA receptor-mediated responses in mouse substantia nigra pars compacta dopamine neurons. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26707656/ · DOI 10.1016/j.neuropharm.2015.12.013
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 208–214

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Ddo-knockout mouse nigral neuron transporter-blocker experiments. · source_derived_draft · unverified_draft

    ## d-aspartate-uptake-buffer Uptake can buffer excitation when breakdown is impaired. EAAT inhibition strongly potentiated D-aspartate-evoked, but not L-aspartate-evoked, currents in Ddo-knockout mouse neurons. Model: Ddo-knockout mouse nigral neuron transporter-blocker experiments. Limitations: A protective adaptation is an interpretation; human transporter failure and dietary consequences were not tested. Evidence access: Primary abstract Persistent elevation of D-Aspartate enhances NMDA receptor-mediated responses in mouse substantia nigra pars compacta dopamine neurons. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26707656/ · DOI 10.1016/j.neuropharm.2015.12.013
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

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