8 research outputs found
Early Developmental Marginal Zinc Deficiency Affects Neurogenesis Decreasing Neuronal Number and Altering Neuronal Specification in the Adult Rat Brain
During pregnancy, a decreased availability of zinc to the fetus can disrupt the development of the central nervous system leading to defects ranging from severe malformations to subtle neurological and cognitive effects. We previously found that marginal zinc deficiency down-regulates the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and affects neural progenitor cell (NPC) proliferation. This study investigated if marginal zinc deficiency during gestation in rats could disrupt fetal neurogenesis and affect the number and specification of neurons in the adult offspring brain cortex. Rats were fed a marginal zinc deficient or adequate diet throughout gestation and until postnatal day (P) 2, and subsequently the zinc adequate diet until P56. Neurogenesis was evaluated in the offspring at embryonic day (E)14, E19, P2, and P56 measuring parameters of NPC proliferation and differentiation by Western blot and/or immunofluorescence. At E14 and E19, major signals (i.e., ERK1/2, Sox2, and Pax6) that stimulate NPC proliferation and self-renewal were markedly downregulated in the marginal zinc deficient fetal brain. These alterations were associated to a lower number of Ki67 positive cells in the ventricular (VZs) and subventricular zones (SVZs). Following the progression of NPCs into intermediate progenitor cells (IPCs) and into neurons, Pax6, Tbr2 and Tbr1 were affected in the corresponding areas of the brain at E19 and P2. The above signaling alterations led to a lower density of neurons and a selective decrease of glutamatergic neurons in the young adult brain cortex exposed to maternal marginal zinc deficiency from E14 to P2. Current results supports the concept that marginal zinc deficiency during fetal development can disrupt neurogenesis and alter cortical structure potentially leading to irreversible neurobehavioral impairments later in life
Combined Effects of Gestational Phthalate Exposure and Zinc Deficiency on Steroid Metabolism and Growth
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Combined Effects of Gestational Phthalate Exposure and Zinc Deficiency on Steroid Metabolism and Growth
Disruption of steroid hormone signaling has been implicated independently in the developmental abnormalities resulting from maternal phthalate plasticizer exposure and developmental zinc deficiency. This study investigated if secondary zinc deficiency may result from dietary exposure to a low level of di-2-ethylhexyl phthalate (DEHP) through gestation and if this could be associated with altered steroid metabolism. The interaction between marginal zinc nutrition and DEHP exposure to affect pregnancy outcome, zinc status, and steroid metabolism was also assessed. For this purpose, rats were fed a diet containing an adequate (25 mg/kg) or marginal (10 mg/kg) level of zinc without or with DEHP (300 mg/kg) from gestation day (GD) 0 until GD 19. Steroid profiles were measured in dam liver, plasma, adrenal glands, and in fetal liver by UPLC/MS-MS. In dams fed the adequate zinc diet, DEHP exposure decreased maternal weight gain and led to hepatic acute-phase response and zinc accumulation. The latter could compromise zinc availability to the fetus. DEHP and marginal zinc deficiency caused several adverse effects on the maternal and fetal steroid profiles. Interactions between DEHP exposure and marginal zinc deficient nutrition affected 17OH pregnenolone and corticosterone, while pregnenolone levels were specifically affected by DEHP exposure. Maternal marginal zinc deficiency specifically affected maternal progesterone and aldosterone, and presented evidence of increased androgen aromatization activity in maternal and fetal tissues. Results stress the potential major impact of mild DEHP exposure on maternal/fetal steroid metabolism that can be potentiated by nutritional and chronic disease states leading to zinc deficiency
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Early Developmental Marginal Zinc Deficiency Affects Neurogenesis Decreasing Neuronal Number and Altering Neuronal Specification in the Adult Rat Brain.
During pregnancy, a decreased availability of zinc to the fetus can disrupt the development of the central nervous system leading to defects ranging from severe malformations to subtle neurological and cognitive effects. We previously found that marginal zinc deficiency down-regulates the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and affects neural progenitor cell (NPC) proliferation. This study investigated if marginal zinc deficiency during gestation in rats could disrupt fetal neurogenesis and affect the number and specification of neurons in the adult offspring brain cortex. Rats were fed a marginal zinc deficient or adequate diet throughout gestation and until postnatal day (P) 2, and subsequently the zinc adequate diet until P56. Neurogenesis was evaluated in the offspring at embryonic day (E)14, E19, P2, and P56 measuring parameters of NPC proliferation and differentiation by Western blot and/or immunofluorescence. At E14 and E19, major signals (i.e., ERK1/2, Sox2, and Pax6) that stimulate NPC proliferation and self-renewal were markedly downregulated in the marginal zinc deficient fetal brain. These alterations were associated to a lower number of Ki67 positive cells in the ventricular (VZs) and subventricular zones (SVZs). Following the progression of NPCs into intermediate progenitor cells (IPCs) and into neurons, Pax6, Tbr2 and Tbr1 were affected in the corresponding areas of the brain at E19 and P2. The above signaling alterations led to a lower density of neurons and a selective decrease of glutamatergic neurons in the young adult brain cortex exposed to maternal marginal zinc deficiency from E14 to P2. Current results supports the concept that marginal zinc deficiency during fetal development can disrupt neurogenesis and alter cortical structure potentially leading to irreversible neurobehavioral impairments later in life
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Gestational marginal zinc deficiency impaired fetal neural progenitor cell proliferation by disrupting the ERK1/2 signaling pathway.
This study investigated if a marginal zinc deficiency during gestation in rats could affect fetal neural progenitor cell (NPC) proliferation through a down-regulation of the extracellular signal-regulated kinase (ERK1/2) signaling pathway. Rats were fed a marginally zinc-deficient or adequate diet from the beginning of gestation until embryonic day (E)19. The proportion of proliferating cells in the E19 fetal ventricular zone was decreased by marginal zinc deficiency. Immunostaining for phosphorylated ERK1/2 in the cerebral cortex was decreased in the marginal zinc fetuses, and this effect was strongest in the ventricular zone. Furthermore, phosphorylation of the upstream mitogen-activated ERK kinases (MEK1/2) was not affected, suggesting that marginal zinc deficiency could have increased ERK-directed phosphatase activity. Similar findings were observed in cultured rat embryonic cortical neurons and in IMR-32 neuroblastoma cells, in which zinc-deficiency decreased ERK1/2 phosphorylation without affecting MEK1/2 phosphorylation. Indeed, zinc deficiency increased the activity of the ERK-directed phosphatase protein phosphatase 2A (PP2A) in the fetal cortex and IMR-32 cells. Inhibition of PP2A with okadaic acid prevented the decrease in ERK phosphorylation and proliferation of zinc-deficient IMR-32 cells. Together these results demonstrated that decreased zinc availability reduces ERK1/2 signaling and decreased NPC proliferation as a consequence of PP2A activation. Disruption of fetal neurogenesis could underlie irreversible neurobehavioral impairments observed after even marginal zinc nutrition during a critical period of early brain development