ArticleThe Journal of clinical investigation2017
Deficiency of tumor suppressor NDRG2 leads to attention deficit and hyperactive behavior.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Attention Deficit Hyperactivity Disorder (ADHD) and Polyphenols: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Parallel anterior cingulate cortex pathways underlie dissociable social and attentional outputs.Science advances · 2026Article
- Aniracetam restores the excitation-inhibition balance of neurotransmitters in the prefrontal cortex of mice with ADHD.Scientific reports · 2026Article
- The selenocysteine-containing protein SELENOT maintains dopamine signaling in the midbrain to protect mice from hyperactivity disorder.The EMBO journal · 2025Article
- Aniracetam Ameliorates Attention Deficit Hyperactivity Disorder Behavior in Adolescent Mice.eNeuro · 2025Article
- Neurodevelopmental disorders and gut-brain interactions: exploring the therapeutic potential of pycnogenol through microbial-metabolic-neural networks.Frontiers in cellular and infection microbiology · 2025Review
- Transformation of A1/A2 Astrocytes Participates in Brain Ischemic Tolerance Induced by Cerebral Ischemic Preconditioning via Inhibiting NDRG2.Neurochemical research · 2024Article
- Learning and Memory Impairments With Attention-Deficit/Hyperactivity Disorder.Physiological research · 2024Review
- Astrocytic NDRG2-PPM1A interaction exacerbates blood-brain barrier disruption after subarachnoid hemorrhage.Science advances · 2022Article
- Deficiency of transmembrane AMPA receptor regulatory protein γ-8 leads to attention-deficit hyperactivity disorder-like behavior in mice.Zoological research · 2022Article
- Mice with mutations in Trpm1, a gene in the locus of 15q13.3 microdeletion syndrome, display pronounced hyperactivity and decreased anxiety-like behavior.Molecular brain · 2021Article
- [Effect of Long-time Postnatal Exposure to Sevoflurane on Causing Attention-deficit/Hyperactivity Disorder in Rats].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2021Article
- Article
- NDRG2 is expressed on enteric glia and altered in conditions of inflammation and oxygen glucose deprivation/reoxygenation.Journal of molecular histology · 2021Article
- Roles of N-myc downstream-regulated gene 2 in the central nervous system: molecular basis and relevance to pathophysiology.Anatomical science international · 2021Review
- NDRG2 regulates adherens junction integrity to restrict colitis and tumourigenesis.EBioMedicine · 2020Article
- NDRG2 attenuates ischemia-induced astrocyte necroptosis via the repression of RIPK1.Molecular medicine reports · 2020Article
- Astrocyte-specific NDRG2 gene: functions in the brain and neurological diseases.Cellular and molecular life sciences : CMLS · 2020Review
- Astrocytic histone deacetylase 2 facilitates delayed depression and memory impairment after subarachnoid hemorrhage by negatively regulating glutamate transporter-1.Annals of translational medicine · 2020Article
- NDRG2 Protects the Brain from Excitotoxicity by Facilitating Interstitial Glutamate Uptake.Translational stroke research · 2020Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent psychiatric disorder in children. Although an imbalance of excitatory and inhibitory inputs has been proposed as contributing to this disorder, the mechanisms underlying this highly heterogeneous disease remain largely unknown. Here, we show that N-myc downstream-regulated gene 2 (NDRG2) deficiency is involved in the development of ADHD in both mice and humans. Ndrg2-knockout (Ndrg2-/-) mice exhibited ADHD-like symptoms characterized by attention deficits, hyperactivity, impulsivity, and impaired memory. Furthermore, interstitial glutamate levels and excitatory transmission were markedly increased in the brains of Ndrg2-/- mice due to reduced astroglial glutamate clearance. We developed an NDRG2 peptide that rescued astroglial glutamate clearance and reduced excitatory glutamate transmission in NDRG2-deficient astrocytes. Additionally, NDRG2 peptide treatment rescued ADHD-like hyperactivity in the Ndrg2-/- mice, while routine methylphenidate treatment had no effect on hyperactivity in these animals. Finally, children who were heterozygous for rs1998848, a SNP in NDRG2, had a higher risk of ADHD than children who were homozygous for rs1998848. Our results indicate that NDRG2 deficiency leads to ADHD phenotypes and that impaired astroglial glutamate clearance, a mechanism distinct from the well-established dopamine deficit hypothesis for ADHD, underlies the resultant behavioral abnormalities.
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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.