Intracellular zinc signaling influences NMDA receptor function by enhancing the interaction of ZnT1 with GluN2A

Krall, Rebecca; Gale, Jenna R.; Ross, Madeline M.; Tzounopoulos, Thanos; Aizenman, Elias

doi:10.1016/j.neulet.2022.136896

Cited by 8 publications

(3 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Synaptic zinc is generally regarded as an N-methyl-d-aspartate (NMDA) receptor antagonist. It therapeutically targets NMDA receptors to modulate excitatory amino acid (glutamatergic) and inhibitory (GABAergic) neurotransmission, producing an antidepressant-like effect [ 30 , 31 ]. According to an animal study, blocking NMDA receptors may reduce the protective benefits of zinc on depressive-related symptoms, further suggesting that NMDA receptors mediate the antidepressant properties of zinc [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Causal Associations between Various Serum Minerals and Risk of Depression: A Mendelian Randomization Study

Wang,

Liu,

Yang

2024

Actas Esp Psiquiatr

View full text Add to dashboard Cite

Background: Previous observational studies have discovered a connection between depression and mineral status. Confirming this potential connection is challenging due to confounding factors and potential reverse causality which is inherent in observational studies. Materials and Methods: We performed a Mendelian randomization (MR) analysis to estimate the causal association of serum minerals with depression. Leveraging summary-level data on depression, a genome-wide association study (GWAS) was applied. The data on serum minerals were collected from the FinnGen Biobank database. MR assessments representing causality were produced by inverse-variance weighted approaches with multiplicative random and fixed effects. Result: Sensitivity analyses were performed to validate the reliability of the results. A noteworthy correlation emerged between serum zinc levels and reduced risk of depression. An odds ratio (OR) of 0.917 for depression associated with a one standard deviation increase in serum zinc levels (OR = 0.968; 95% CI = 0.953–0.984, p = 1.19 × 10-4, random effects model inverse variance weighted (IVW)); (OR = 0.928; 95% CI = 0.634–1.358, p = 0.766, MR Egger). Sensitivity assessments supported this causation. However, the risk of depression did not exhibit an association with other minerals. Conclusions: In summary, a higher zinc concentration is causally associated with a reduced depression risk. This MR outcome may assist clinicians in the regulation of specific mineral intake, particularly for high-risk patients with serum zinc deficiencies.

show abstract

Section: Discussionmentioning

confidence: 99%

Genetic Causal Associations between Various Serum Minerals and Risk of Depression: A Mendelian Randomization Study

Wang,

Liu,

Yang

2024

Actas Esp Psiquiatr

View full text Add to dashboard Cite

show abstract

“…Hence, lower serum zinc concentrations could compromise serotonin and BDNF activity and diminish neurogenesis, which may be the pathophysiology of depression [ 25 ]. Zinc is a modulator of excitatory (glutamate) and inhibitory (GABA) neurotransmitters [ 90 ]: zinc binds to GluN2A subunit via zinc transporter 1 and inhibits N-methyl-d-aspartic acid (NMDA) receptor function [ 91 ]; zinc activates the zinc-sensing receptor GPR39 to regulate glutamate and GABA, maintaining the brain’s excitatory-inhibitory balance [ 23 ]. Consequently, reduced zinc concentrations may trigger glutamate release and elicit neuronal excitotoxicity, which contributes to depression [ 92 ].…”

Section: Discussionmentioning

confidence: 99%

Association between serum copper, zinc, and selenium concentrations and depressive symptoms in the US adult population, NHANES (2011–2016)

et al. 2023

View full text Add to dashboard Cite

Background Evidence suggests that alterations in serum trace element concentrations are closely associated with mental illness. However, studies on the relationship between serum copper, zinc, and selenium concentrations and depressive symptoms are limited and with controversial results. We aimed to investigate the association between serum concentrations of these trace elements and depressive symptoms in US adults. Methods Data from the National Health and Nutrition Examination Survey (NHANES) (2011–2016) were used in this cross-sectional study. The Patient Health Questionnaire-9 Items (PHQ-9) was employed to assess depressive symptoms. Multiple logistic regression was performed to determine the relationship between the serum concentrations of copper, zinc, and selenium and depressive symptoms. Results A total of 4552 adults were included. Subjects with depressive symptoms had higher serum copper concentrations (123.88 ± 1.87) than those without depressive symptoms (116.99 ± 0.86) (p < 0.001). In Model 2, weighted logistic regression analysis showed that the second (Q2) quartile of zinc concentrations (odds ratio [OR] = 1.534, 95% confident interval [CI]: 1.018 to 2.313) were significantly associated with an increased risk of depressive symptoms. Subgroup analysis revealed that the third (Q3) and fourth (Q4) quartiles of copper concentrations (Q3: OR = 2.699, 95% CI: 1.285 to 5.667; Q4: OR = 2.490, 95% CI: 1.026 to 6.046) were also positively associated with depressive symptoms in obese individuals after controlling for all confounders. However, no significant relationship between serum selenium concentrations and depressive symptoms was observed. Conclusions Obese US adults with high serum copper concentrations, as well as US adults in general with low serum zinc concentrations, were susceptible to depressive symptoms. Nevertheless, the causal mechanisms underlying these relationships need to be further explored.

show abstract

“…Zinc is also essential for cognitive performance and is involved in glutamatergic transmission, which has short-term and long-term mental effects [ 17 ]. Zinc blocks NMDA receptors and is an intracellular signal factor involved in numerous proteins, and its deficiency may impair neurotransmission [ 143 ]. Furthermore, Zn acts as a co-transmitter with glutamate, preventing excitotoxicity, and is an important trophic factor, providing essential nutrients for enzymes with anabolic function in synapse areas undergoing permanent learning processes [ 17 ].…”

Section: Mineral Imbalancesmentioning

confidence: 99%

Advances in the Treatment of Autism Spectrum Disorder: Current and Promising Strategies

Yenkoyan,

Ounanian,

Mirumyan

et al. 2024

CMC

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) is an umbrella term for developmental disorders characterized by social and communication impairments, language difficulties, restricted interests, and repetitive behaviors. Current management approaches for ASD aim to resolve its clinical manifestations based on the type and severity of the disability. Although some medications like risperidone show potential in regulating ASD-associated symptoms, a comprehensive treatment strategy for ASD is yet to be discovered. To date, identifying appropriate therapeutic targets and treatment strategies remains challenging due to the complex pathogenesis associated with ASD. Therefore, a comprehensive approach must be tailored to target the numerous pathogenetic pathways of ASD. From currently viable and basic treatment strategies, this review explores the entire field of advancements in ASD management up to cutting-edge modern scientific research. A novel systematic and personalized treatment approach is suggested, combining the available medications and targeting each symptom accordingly. Herein, summarize and categorize the most appropriate ways of modern ASD management into three distinct categories: current, promising, and prospective strategies.

show abstract

Intracellular zinc signaling influences NMDA receptor function by enhancing the interaction of ZnT1 with GluN2A

Cited by 8 publications

References 45 publications

Genetic Causal Associations between Various Serum Minerals and Risk of Depression: A Mendelian Randomization Study

Genetic Causal Associations between Various Serum Minerals and Risk of Depression: A Mendelian Randomization Study

Association between serum copper, zinc, and selenium concentrations and depressive symptoms in the US adult population, NHANES (2011–2016)

Advances in the Treatment of Autism Spectrum Disorder: Current and Promising Strategies

Contact Info

Product

Resources

About