ArticleTranslational psychiatry2018
DISC1 regulates lactate metabolism in astrocytes: implications for psychiatric disorders.
Article in Translational psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- NPAS3-regulated astrocyte mitochondrial bioenergetics is required for cognition.Science advances · 2026Article
- From brain bioenergetics to hypothalamic glucoregulation: A shared-systems hypothesis for intrinsic dysglycemia in schizophrenia.Reviews in endocrine & metabolic disorders · 2026Review
- Lactate restores PGC1α and BDNF expression rescuing cognitive impairments in a mouse model for schizophrenia.Behavioural brain research · 2026Article
- Metabolic Mechanisms in Electroconvulsive Therapy for Schizophrenia: Role, Potential and Future Directions.International journal of molecular sciences · 2026Review
- Article
- From metabolism to mood regulation: astrocytes as a driver of depression.Frontiers in cellular neuroscience · 2026Review
- Neural Metabolic Networks: Key Elements of Healthy Brain Function.Journal of neurochemistry · 2025Review
- Neuroimaging genetics approaches to identify new biomarkers for the early diagnosis of autism spectrum disorder.Molecular psychiatry · 2023Review
- Lactate: A Theranostic Biomarker for Metabolic Psychiatry?Antioxidants (Basel, Switzerland) · 2023Review
- Article
- Deciphering spatial domains from spatially resolved transcriptomics with an adaptive graph attention auto-encoder.Nature communications · 2022Article
- Clinical translational neuroimaging of the antioxidant effect of N-acetylcysteine on neural microstructure.Magnetic resonance in medicine · 2022Article
- Human iPSC-Derived Glia as a Tool for Neuropsychiatric Research and Drug Development.International journal of molecular sciences · 2021Review
- Polychlorinated biphenyls induce oxidative stress and metabolic responses in astrocytes.Neurotoxicology · 2021Article
- Article
- MCT1 Deletion in Oligodendrocyte Lineage Cells Causes Late-Onset Hypomyelination and Axonal Degeneration.Cell reports · 2021Article
- Oxidative Stress-Related Mechanisms in Schizophrenia Pathogenesis and New Treatment Perspectives.Oxidative medicine and cellular longevity · 2021Review
- Astrocyte Bioenergetics and Major Psychiatric Disorders.Advances in neurobiology · 2021Review
- Astrocyte-Derived Lactate Modulates the Passive Coping Response to Behavioral Challenge in Male Mice.Neuroscience bulletin · 2021Article
- Universal Glia to Neurone Lactate Transfer in the Nervous System: Physiological Functions and Pathological Consequences.Biosensors · 2020Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Our knowledge of how genetic risk variants contribute to psychiatric disease is mainly limited to neurons. However, the mechanisms whereby the same genetic risk factors could affect the physiology of glial cells remain poorly understood. We studied the role of a psychiatric genetic risk factor, Disrupted-In-Schizophrenia-1 (DISC1), in metabolic functions of astrocytes. We evaluated the effects of knockdown of mouse endogenous DISC1 (DISC1-KD) and expression of a dominant-negative, C-terminus truncated human DISC1 (DN-DISC1) on the markers of energy metabolism, including glucose uptake and lactate production, in primary astrocytes and in mice with selective expression of DN-DISC1 in astrocytes. We also assessed the effects of lactate treatment on altered affective behaviors and impaired spatial memory in DN-DISC1 mice. Both DISC1-KD and DN-DISC1 comparably decreased mRNA and protein levels of glucose transporter 4 and glucose uptake by primary astrocytes. Decreased glucose uptake was associated with reduced oxidative phosphorylation and glycolysis as well as diminished lactate production in vitro and in vivo. No significant effects of DISC1 manipulations in astrocytes were observed on expression of the subunits of the electron transport chain complexes or mitofilin, a neuronal DISC1 partner. Lactate treatment rescued the abnormal behaviors in DN-DISC1 male and female mice. Our results suggest that DISC1 may be involved in the regulation of lactate production in astrocytes to support neuronal activity and associated behaviors. Abnormal expression of DISC1 in astrocytes and resulting abnormalities in energy supply may be responsible for aspects of mood and cognitive disorders observed in patients with major psychiatric illnesses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.