ArticleNeuron2019
Mitochondrial Dysfunction Leads to Cortical Under-Connectivity and Cognitive Impairment.
Article in Neuron, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 2 of them syntheses that pooled it.
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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.
The trial behind it
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
98 citing papers in PubMed, 2 syntheses or guidelines pooled it, 166 citations in OpenAlex.
- Mitochondrial Dysfunction and Cognitive Impairment in Schizophrenia: The Role of Inflammation.Schizophrenia bulletin · 2025Pooled it
- Neurometabolite differences in Autism as assessed with Magnetic Resonance Spectroscopy: A systematic review and meta-analysis.Neuroscience and biobehavioral reviews · 2024Pooled it
- Cerebellar mitochondrial dysfunction coincides with structural and behavioral abnormalities in 3q29Del mice.bioRxiv : the preprint server for biology · 2026Article
- An antioxidant therapy elicits distinct transcriptome responses in 22q11-deleted upper layer cortical projection neurons.Disease models & mechanisms · 2026Article
- Strong connections of locally clustered neurons in the upper-layer cortex underlie schizophrenia-related auditory deviance detection.Science advances · 2026Article
- The Disease Gene THAP12 is a Transcriptional Regulator of Mitochondrial ETC Complex I.bioRxiv : the preprint server for biology · 2026Article
- Gene dosage effects of 22q11.2 copy number variants on in-vivo measures of white matter axonal density and dispersion.Molecular psychiatry · 2026Article
- Pharmacological rescue of mitochondrial dysfunction, neurite degeneration, and premature death of ALS and AD iPSC-derived neurons.bioRxiv : the preprint server for biology · 2026Article
- Transcriptomic and phenotypic convergence of neurodevelopmental disorder risk genes in vitro and in vivo.Nature neuroscience · 2026Article
- Mitochondrial dynamics in neurodevelopment and neurodevelopmental disorders.Nature reviews. Neuroscience · 2026Review
- Developmental Alterations in the Diffusion Tensor Imaging Analysis Along the Perivascular Space Index Suggest Possible Glymphatic-Related Mechanisms Underlying Excitation/Inhibition Imbalance and Psychosis Vulnerability in 22q11.2 Deletion Syndrome.Biological psychiatry global open science · 2026Article
- Maternal Immune Activation Leads to Mitochondrial Dysfunction and a Social Deficit in Offspring That Is Reversed by Nicotinamide Riboside.Nutrients · 2026Article
- Convergent effects of neurodevelopmental disorder-associated variants at mitochondria.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial CaNature metabolism · 2026Article
- Charting Brain Structure in 22q11.2 Deletion Syndrome with Clinical Neuroimaging.medRxiv : the preprint server for health sciences · 2026Article
- Suppressive Genetic Interactions Between Haploinsufficient Mitochondrial Genes Encoded in the 22q11.2 Microdeletion Locus Define Brain and Cardiac Phenotypes.bioRxiv : the preprint server for biology · 2026Article
- Multimodal neuroimaging reveals brain neurochemical disturbances associated with superoxide dismutase in first-episode drug-naïve schizophrenia.Translational psychiatry · 2026Article
- The systemic effects of 22q11.2 deletion syndrome on immunity.Journal of human immunity · 2026Review
- Metabolic changes in mTOR pathway-associated cortical malformation.Frontiers in neuroscience · 2026Review
- Distinct cellular and transcriptional mechanisms mediate an antioxidant therapeutic response in 22q11-deleted upper layer cortical projection neurons.bioRxiv : the preprint server for biology · 2025Article
38 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Under-connectivity between cerebral cortical association areas may underlie cognitive deficits in neurodevelopmental disorders, including the 22q11.2 deletion syndrome (22q11DS). Using the LgDel 22q11DS mouse model, we assessed cellular, molecular, and developmental origins of under-connectivity and its consequences for cognitive function. Diminished 22q11 gene dosage reduces long-distance projections, limits axon and dendrite growth, and disrupts mitochondrial and synaptic integrity in layer 2/3 but not 5/6 projection neurons (PNs). Diminished dosage of Txnrd2, a 22q11 gene essential for reactive oxygen species catabolism in brain mitochondria, recapitulates these deficits in WT layer 2/3 PNs; Txnrd2 re-expression in LgDel layer 2/3 PNs rescues them. Anti-oxidants reverse LgDel- or Txnrd2-related layer 2/3 mitochondrial, circuit, and cognitive deficits. Accordingly, Txnrd2-mediated oxidative stress reduces layer 2/3 connectivity and impairs cognition in the context of 22q11 deletion. Anti-oxidant restoration of mitochondrial integrity, cortical connectivity, and cognitive behavior defines oxidative stress as a therapeutic target in neurodevelopmental disorders.
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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.