Prenatal zinc supplementation attenuates lipopolysaccharide-induced behavioral impairments in maternal immune activation model

Alizadeh, Faezeh; Davoodian, Nahid; Kazemi, Haniyeh; Ghasemi-Kasman, Maryam; Shaerzadeh, Fatemeh

doi:10.1016/j.bbr.2019.112247

Cited by 16 publications

(20 citation statements)

References 54 publications

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“…In recent years, it has been found that zinc supplementation throughout pregnancy in LPS-treated rats increased glutamate decarboxylase 67 (GAD67) expression in male pups but did not affect catechol-O-methyltransferase (COMT), while no changes in either GAD67 or COMT expression levels were found in female pups. This study highlighted the importance of zinc supplementation throughout pregnancy, which may limit the adverse effect of maternal infection on fetal neurodevelopment [ 20 ].…”

Section: Zinc and Neurobiologymentioning

confidence: 99%

Zinc in Cognitive Impairment and Aging

et al. 2022

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Zinc, an essential micronutrient for life, was first discovered in 1869 and later found to be indispensable for the normal development of plants and for the normal growth of rats and birds. Zinc plays an important role in many physiological and pathological processes in normal mammalian brain development, especially in the development of the central nervous system. Zinc deficiency can lead to neurodegenerative diseases, mental abnormalities, sleep disorders, tumors, vascular diseases, and other pathological conditions, which can cause cognitive impairment and premature aging. This study aimed to review the important effects of zinc and zinc-associated proteins in cognitive impairment and aging, to reveal its molecular mechanism, and to highlight potential interventions for zinc-associated aging and cognitive impairments.

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Section: Zinc and Neurobiologymentioning

confidence: 99%

Zinc in Cognitive Impairment and Aging

et al. 2022

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“…In animals, comparing dams assigned to a DHA‐deficient diet with those with a DHA‐enriched diet showed that DHA‐enriched animals have offspring with less behavioural problems compared with the DHA‐deficient counterpart 82 . Likewise, memory impairment of MIA model offspring was restored by zinc supplementation during pregnancy, 83 although the translational relevance of this experiment for therapeutic interventions in humans is low. Pre‐treatment of vitamin D (Vit.D; 25‐hydroxycholecalciferol) during experimental MIA induction prevents stereotyped digging and social withdrawal in the progeny 84 .…”

Section: Towards An Immunological Treatment Of Asdmentioning

confidence: 99%

Immune regulation of neurodevelopment at the mother–foetus interface: the case of autism

et al. 2020

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by deficits in social communication and stereotypical behaviours. ASD’s aetiology remains mostly unclear, because of a complex interaction between genetic and environmental factors. Recently, a strong consensus has developed around ASD’s immune‐mediated pathophysiology, which is the subject of this review. For many years, neuroimmunological studies tried to understand ASD as a prototypical antibody‐ or cell‐mediated disease. Other findings indicated the importance of autoimmune mechanisms such as familial and individual autoimmunity, adaptive immune abnormalities and the influence of infections during gestation. However, recent studies have challenged the idea that autism may be a classical autoimmune disease. Modern neurodevelopmental immunology shows the double‐edged nature of many immune effectors, which can be either beneficial or detrimental depending on tissue homeostasis, stressors, neurodevelopmental stage, inherited and de novo gene mutations and other variables. Nowadays, mother–child interactions in the prenatal environment appear to be crucial for the occurrence of ASD. Studies of animal maternal–foetal immune interaction are being fruitfully carried out using different combinations of type and timing of infection, of maternal immune response and foetal vulnerability and of resilience factors to hostile events. The derailed neuroimmune crosstalk through the placenta initiates and maintains a chronic foetal neuroglial activation, eventually causing the alteration of neurogenesis, migration, synapse formation and pruning. The importance of pregnancy can also allow early immune interventions, which can significantly reduce the increasing risk of ASD and its heavy social burden.

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“…In addition to being involved in innate and adaptive immunity, zinc is strongly required for the normal brain functions and fetal hypozincemia can eventually lead to neurodevelopmental damage in the offspring (Chua, Cowley, Manavis, Rofe, & Coyle, 2012;Coyle et al, 2009). In support of this possibility are findings of several studies demonstrating the beneficial effect of zinc supplementation during pregnancy to protect against fetal death, neurobehavioral impairments, autistic-like behaviors, and preterm delivery induced by LPS with unclear molecular mechanism (Alizadeh et al, 2020;Chen et al, 2012;Chua et al, 2012;Kirsten et al, 2015). One possible mechanism is that zinc supplementation during pregnancy might counteract the LPS-induced reduction of zinc availability to the fetus and ultimately prevent the abnormal neurodevelopment in the progeny.…”

Section: Discussionmentioning

confidence: 96%

“…In our previous study, we demonstrated that prenatal exposed to LPS on GD15 and 16 results in significant behavioral impairments in adult offspring being a phenotype associated with schizophrenia (Alizadeh et al, 2020). Of note, these behavioral deficits were observed only among male pups, which were selected for further investigation.…”

Section: Discussionmentioning

confidence: 97%

“…All experimental procedures were based on the National Institutes of Health guide for the care and use of laboratory animals and approved by the ethical committee of HUMS (IR.HUMS.REC.1397.276). To minimize the number and suffering of animals based on the Three Rs principle, we shared the treated animals in two other published articles (Alizadeh et al, 2020;Mousaviyan et al, 2021).…”

Section: Animalmentioning

confidence: 99%

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Prenatal Zinc Supplementation Ameliorates Hippocampal Astrocytes Activation and Inflammatory Cytokines Expression Induced by Lipopolysaccharide in a Rat Model of Maternal Immune Activation

Savareh

Davoodian

Mousaviyan

et al. 2022

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Objective: There is evidence that gestational exposure to lipopolysaccharide (LPS) results in fetal zinc deficiency, and eventually neurodevelopmental abnormalities. In this study, we utilized a rat model of maternal immune activation (MIA) to investigate the possible neuroprotective effect of zinc supplementation throughout pregnancy on hippocampal astrocytes activation as well as inflammatory cytokines expression in adult offspring. Methods: Pregnant rats received intraperitoneal injections of either LPS (0.5 mg/kg) or saline at gestational day (GD) 15 and 16 and orally gavaged with zinc sulfate (30 mg/kg) throughout pregnancy. Astrocyte density and histological assessment were evaluated in the hippocampus of adult offspring at postnatal day (PND) 60-62. Also, the mRNA levels of IL-6, TNF-α, IL-1β, NF-κB, and glial fibrillary acidic protein (GFAP) were measured using qPCR analysis. Results: Prenatal exposure to LPS resulted in up-regulated expression levels of IL-6, TNF-α, NF-κB, and GFAP in the hippocampus of adult pups. Moreover, offspring from LPS group showed an increased astrocyte density in CA1 region with no histological alterations in CA1 and CA3 areas. Conversely, maternal zinc supplementation ameliorated these inflammatory alterations induced by LPS. Discussion: This study provides support for the premise that zinc supplementation during pregnancy might be an early treatment option to inhibit hippocampal inflammation induced by the maternal immune response to infectious agents.

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Prenatal zinc supplementation attenuates lipopolysaccharide-induced behavioral impairments in maternal immune activation model

Cited by 16 publications

References 54 publications

Zinc in Cognitive Impairment and Aging

Zinc in Cognitive Impairment and Aging

Immune regulation of neurodevelopment at the mother–foetus interface: the case of autism

Prenatal Zinc Supplementation Ameliorates Hippocampal Astrocytes Activation and Inflammatory Cytokines Expression Induced by Lipopolysaccharide in a Rat Model of Maternal Immune Activation

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