ArticleMolecular psychiatry2024
Nuclear GAPDH in cortical microglia mediates cellular stress-induced cognitive inflexibility.
Article in Molecular psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 7 citations in OpenAlex.
- Next-generation precision medicine for pain.Molecular psychiatry · 2026Article
- SIRT1 deacetylates GAPDH to drive microglial glycolysis and neuroinflammation.Frontiers in immunology · 2026Article
- Identification of Potential Therapeutic Agents for Primary Amebic Meningoencephalitis Using Text Mining and Bioinformatics Analyses.Analytical cellular pathology (Amsterdam) · 2026Article
- Stress-induced nuclear GAPDH: Scientific update and clinical application.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Beyond energy: how TCA cycle-derived metabolites regulate gene expression and inflammation in the nucleus.Journal of inflammation (London, England) · 2025Review
- [Targets and Molecular Mechanisms of Salidroside in Improving High-Altitude Cognitive Function].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- Next-generation precision medicine for suicidality prevention.Translational psychiatry · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 3 institutions in 2 countries.
Funding
Abstract
We report a mechanism that underlies stress-induced cognitive inflexibility at the molecular level. In a mouse model under subacute cellular stress in which deficits in rule shifting tasks were elicited, the nuclear glyceraldehyde dehydrogenase (N-GAPDH) cascade was activated specifically in microglia in the prelimbic cortex. The cognitive deficits were normalized with a pharmacological intervention with a compound (the RR compound) that selectively blocked the initiation of N-GAPDH cascade without affecting glycolytic activity. The normalization was also observed with a microglia-specific genetic intervention targeting the N-GAPDH cascade. At the mechanistic levels, the microglial secretion of High-Mobility Group Box (HMGB), which is known to bind with and regulate the NMDA-type glutamate receptors, was elevated. Consequently, the hyperactivation of the prelimbic layer 5 excitatory neurons, a neural substrate for cognitive inflexibility, was also observed. The upregulation of the microglial HMGB signaling and neuronal hyperactivation were normalized by the pharmacological and microglia-specific genetic interventions. Taken together, we show a pivotal role of cortical microglia and microglia-neuron interaction in stress-induced cognitive inflexibility. We underscore the N-GAPDH cascade in microglia, which causally mediates stress-induced cognitive alteration.
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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.