Fetal Alcohol Spectrum Disorder and Iron Homeostasis

Bradley, Regan; Lakpa, Koffi L.; Burd, Michael; Mehta, Sunil; Katušić, Maja; Greenmyer, Jacob R.

doi:10.3390/nu14204223

Cited by 9 publications

(8 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clinical studies have revealed that there are change in iron metabolism in substance use disorders including alcohol abuser. 28 – 31 , 52 , 53 A study conducted in chronic cocaine user revealed that iron content was significantly higher in basal ganglia reward regions than that of control individuals. 54 It was also reported that iron mediates morphine -induced ferritin heavy chain upregulation.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible factor upregulation by roxadustat attenuates drug reward by altering brain iron homoeostasis

Yan,

Li,

et al. 2023

Sig Transduct Target Ther

View full text Add to dashboard Cite

Substance use disorder remains a major challenge, with an enduring need to identify and evaluate new, translational targets for effective treatment. Here, we report the upregulation of Hypoxia-inducible factor-1α (HIF-1α) expression by roxadustat (Rox), a drug developed for renal anemia that inhibits HIF prolyl hydroxylase to prevent degradation of HIF-1α, administered either systemically or locally into selected brain regions, suppressed morphine (Mor)-induced conditioned place preference (CPP). A similar effect was observed with methamphetamine (METH). Moreover, Rox also inhibited the expression of both established and reinstated Mor-CPP and promoted the extinction of Mor-CPP. Additionally, the elevation of HIF-1α enhanced hepcidin/ferroportin 1 (FPN1)-mediated iron efflux and resulted in cellular iron deficiency, which led to the functional accumulation of the dopamine transporter (DAT) in plasma membranes due to iron deficiency-impaired ubiquitin degradation. Notably, iron-deficient mice generated via a low iron diet mimicked the effect of Rox on the prevention of Mor- or METH-CPP formation, without affecting other types of memory. These data reveal a novel mechanism for HIF-1α and iron involvement in substance use disorder, which may represent a potential novel therapeutic strategy for the treatment of drug abuse. The findings also repurpose Rox by suggesting a potential new indication for the treatment of substance use disorder.

show abstract

Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible factor upregulation by roxadustat attenuates drug reward by altering brain iron homoeostasis

Yan,

Li,

et al. 2023

Sig Transduct Target Ther

View full text Add to dashboard Cite

show abstract

“…Maternal consumption of alcoholic drinks during pregnancy has a significant impact on children’s neurodevelopment, intellectual capacity, and learning ability [ 97 , 98 ]. Often, this consumption can lead to the development of Fetal Alcohol Spectrum Disorder (FASD), which is characterized by dysmorphic facial features, fetal growth restriction, and restricted brain growth, resulting in neurobehavioral impairment throughout life [ 97 , 98 , 99 , 100 ]. Although they share similarities, FASD and ASD are distinct entities.…”

Section: The Influence Of Environmental Hazardsmentioning

confidence: 99%

The Autism Spectrum Disorder and Its Possible Origins in Pregnancy

Botelho,

Silva,

Borbely

2024

IJERPH

View full text Add to dashboard Cite

Autism Spectrum Disorder (ASD) belongs to the group of neurodevelopmental disorders, and has a high prevalence, affecting 1 in 100 children according to data from the World Health Organization (WHO). To be diagnosed with ASD, the child must have persistent deficits in communication and social interactions, and restricted and repetitive patterns of behavior, interests, or activities. Despite its prevalence, the etiology of ASD is still uncertain, with multifactorial characteristics, including those associated with the gestational period, where maternal exposure to biological, chemical, or physical hazards occurs, some of which have already been proposed as causes of ASD outcomes. Since pregnancy requires a balance between the maternal–fetal binomial, the breakdown of this balance caused by such environmental hazards can lead to altered fetal neurodevelopment, including ASD. With this firmly in mind, this review aims to compile the most recent data on the gestational causes that may be associated with the development of ASD to help health professionals identify risk factors and act for the prevention and management of ASD.

show abstract

“…When iron storage becomes overloaded, excess Fe 2+ is transported to the labile iron pool (LIP) via divalent metal transporter 1. 34 Bidirectional regulation of iron metabolism is facilitated by cellular proteins. Conversely, Fe 3+ enters cells through the transferrin (TF)/transferrin receptor 1 (TFR-1) transport system, and upregulation of iron-related proteins can also cause intracellular iron overload.…”

Section: Abnormal Iron Metabolism In the Brainmentioning

confidence: 99%

Targeting the ferroptosis crosstalk: novel alternative strategies for the treatment of major depressive disorder

Wang,

Xu,

Huang

et al. 2023

Gen Psych

View full text Add to dashboard Cite

Depression is a major contributor to poor global health and disability, with a recently increasing incidence. Although drug therapy is commonly used to treat depression, conventional antidepressant drugs have several disadvantages, including slow onset, low response rates and severe adverse effects. Therefore, developing effective therapies for depression remains challenging. Although various aetiological theories of depression exist, the underlying mechanisms of depression are complex, and further research is crucial. Moreover, oxidative stress (OS)-induced lipid peroxidation has been demonstrated to trigger ferroptosis. Both OS and ferroptosis are pivotal mechanisms implicated in the pathogenesis of neurological disorders, and investigation of the mediators involved in these processes has emerged as a prominent and active research direction. One previous study revealed that regulatory proteins involved in ferroptosis are implicated in the pathogenesis of depression, and antidepressant drugs could reverse depressive symptoms by inhibiting ferroptosisin vivo, suggesting an important role of ferroptosis in the pathogenesis of depression. Hence, our current comprehensive review offers an up-to-date perspective on the intricate mechanisms involved, specifically concerning ferroptosis and OS in the context of depression, along with promising prospects for using molecular mediators to target ferroptosis. We delineate the key targets of molecular mediators involved in OS and ferroptosis implicated in depression, most notably reactive oxygen species and iron overload. Considering the pivotal role of OS-induced ferroptosis in the pathogenesis of neurological disorders, delving deeper into the underlying subsequent mechanisms will contribute significantly to the identification of novel therapeutic targets for depression.

show abstract

Fetal Alcohol Spectrum Disorder and Iron Homeostasis

Cited by 9 publications

References 92 publications

Hypoxia-inducible factor upregulation by roxadustat attenuates drug reward by altering brain iron homoeostasis

Hypoxia-inducible factor upregulation by roxadustat attenuates drug reward by altering brain iron homoeostasis

The Autism Spectrum Disorder and Its Possible Origins in Pregnancy

Targeting the ferroptosis crosstalk: novel alternative strategies for the treatment of major depressive disorder

Contact Info

Product

Resources

About