Glycogen metabolism in brain and neurons – astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure

Baranowska-Bosiacka, Irena; Falkowska, Anna; Gutowska, Izabela; Gąssowska, Magdalena; Kolasa, Agnieszka; Tarnowski, Maciej; Chibowska, Karina; Goschorska, Marta; Lubkowska, Anna; Chlubek, Dariusz

doi:10.1016/j.tox.2017.09.007

Cited by 20 publications

(8 citation statements)

References 67 publications

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“…Interestingly, the deficits in the KCl-stimulated protein translation observed in our study correlated significantly with blood Pb levels, indicating that synaptic protein translation is a critical molecular pathway linking developmental adversities, such as Pb exposure to their detrimental effects on neuronal communication at the pre- and post-synapse. It should be noted that early life Pb exposure paradigms through drinking water similar to that used in our study are also known to cause significant accumulation of Pb in hippocampal tissues34,72,73 and show a strong and significant correlation with blood Pb levels 74. Moreover, in support of previous studies in human subjects,1,6,8,17,32,84,85 our results suggest that blood Pb levels serve as a valuable diagnostic measure of Pb-mediated dysregulation of neurological functions.…”

Section: Discussionmentioning

confidence: 66%

Developmental lead (Pb)-induced deficits in hippocampal protein translation at the synapses are ameliorated by ascorbate supplementation

Ahmad¹,

Salahuddin²,

Alsamman³

et al. 2018

NDT

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BackgroundLead (Pb) is a persistent environmental neurotoxin and its exposure even in minute quantities has been known to induce neuronal defects. The immature brain is singularly sensitive to Pb neurotoxicity, and its exposure during development has permanent detrimental effects on the brain developmental trajectory and neuronal signaling and plasticity, culminating into compromises in the cognitive and behavioral attributes which persists even later in adulthood. Several molecular pathways have been implicated in the Pb-mediated disruption of neuronal signaling, including elevated oxidative stress, alterations in neurotransmitter biology, and mitochondrial dysfunction. Nevertheless, the neuronal targets and biochemical pathways underlying these Pb-mediated alterations in synaptic development and function have not been completely deduced. In this respect, recent studies have shown that synaptic signaling and its maintenance and plasticity are critically dependent on localized de novo protein translation at the synaptic terminals.Materials and methodsThe present study hence aimed to assess the alterations in the synapse-specific translation induced by developmental Pb exposure. To this end, in vitro protein translation rate was analyzed in the hippocampal synaptoneurosomal fractions of rat pups pre- and postnatally exposed to Pb using a puromycin incorporation assay. Moreover, we evaluated the therapeutic effects of ascorbic acid supplementation against Pb-induced deficits in synapse-localized protein translation.ResultsWe observed a significant loss in the rates of de novo protein translation in synaptoneurosomes of Pb-exposed pups compared to age-matched control pups. Interestingly, ascorbate supplementation lead to an appreciable recovery in Pb-induced translational deficits. Moreover, the deficit in activity-dependent synaptic protein translation was found to correlate significantly with the increase in the blood Pb levels.ConclusionDysregulation of synapse-localized de novo protein translation is a potentially critical determinant of Pb-induced synaptic dysfunction and the consequent deficits in behavioral, social, and psychological attributes of the organisms. In addition, our study establishes ascorbate supplementation as a key ameliorative agent against Pb-induced neurotoxicity.

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Section: Discussionmentioning

confidence: 66%

Developmental lead (Pb)-induced deficits in hippocampal protein translation at the synapses are ameliorated by ascorbate supplementation

Ahmad¹,

Salahuddin²,

Alsamman³

et al. 2018

NDT

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“…Pb also disrupts developmental cortical plasticity, causing dysfunction in neurodevelopment [25]. Moreover, prenatal exposure to Pb affects the activity and expression of key synaptic proteins [10], impairs the functioning of synaptic mitochondria [7,42], disrupts the energy metabolism of neurons and astrocytes, and leads to impaired metabolic cooperation between these cells [43].…”

Section: Introductionmentioning

confidence: 99%

Pre- and Neonatal Exposure to Lead (Pb) Induces Neuroinflammation in the Forebrain Cortex, Hippocampus and Cerebellum of Rat Pups

Chibowska

Korbecki

Gutowska

et al. 2020

IJMS

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Lead (Pb) is a heavy metal with a proven neurotoxic effect. Exposure is particularly dangerous to the developing brain in the pre-and neonatal periods. One postulated mechanism of its neurotoxicity is induction of inflammation. This study analyzed the effect of exposure of rat pups to Pb during periods of brain development on the concentrations of selected cytokines and prostanoids in the forebrain cortex, hippocampus and cerebellum. Methods: Administration of 0.1% lead acetate (PbAc) in drinking water ad libitum, from the first day of gestation to postnatal day 21, resulted in blood Pb in rat pups reaching levels below the threshold considered safe for humans by the Centers for Disease Control and Prevention (10 µg/dL). Enzyme-linked immunosorbent assay (ELISA) method was used to determine the levels of interleukins IL-1β, IL-6, transforming growth factor-β (TGF-β), prostaglandin E2 (PGE2) and thromboxane B2 (TXB2). Western blot and quantitative real-time PCR were used to determine the expression levels of cyclooxygenases COX-1 and COX-2. Finally, Western blot was used to determine the level of nuclear factor kappa B (NF-κB). Results: In all studied brain structures (forebrain cortex, hippocampus and cerebellum), the administration of Pb caused a significant increase in all studied cytokines and prostanoids (IL-1β, IL-6, TGF-β, PGE2 and TXB2). The protein and mRNA expression of COX-1 and COX-2 increased in all studied brain structures, as did NF-κB expression. Conclusions: Chronic pre-and neonatal exposure to Pb induces neuroinflammation in the forebrain cortex, hippocampus and cerebellum of rat pups.

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“…At the cellular level, Pb is considered to be one of the factors inducing inflammation in the brain [11]. The results of our previous work on the expression of selected proteins, enzyme activity, and expression of receptors involved in neurodegenerative processes also show the direct role of Pb in the development of neurodegenerative changes in the brain [12][13][14]. In this study, Pb concentrations at both incubation times resulted in an increase in the mRNA and protein expression of COX-1 and COX-2.…”

Section: Discussionmentioning

confidence: 99%

“…The immune system seems to be one of the more sensitive targets for Pb. Although in low environmental concentrations, Pb does not cause visible damage to the body s main immune cells, it may adversely affect their function [10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Lead (Pb) as a Factor Initiating and Potentiating Inflammation in Human THP-1 Macrophages

Metryka

Kupnicka

Kapczuk

et al. 2020

IJMS

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The aim of this study was to assess the influence of lead (Pb) at low concentrations (imitating Pb levels in human blood in chronic environmental exposure to this metal) on interleukin 1β (IL-1β) and interleukin 6 (IL-6) concentrations and the activity and expression of COX-1 and COX-2 in THP-1 macrophages. Macrophages were cultured in vitro in the presence of Pb at concentrations of: 1.25 μg/dL; 2.5 μg/dL; 5 μg/dL; 10 μg/dL. The first two concentrations of Pb were selected on the basis of our earlier study, which showed that Pb concentration in whole blood (PbB) of young women living in the northern regions of Poland and in the cord blood of their newborn children was within this range (a dose imitating environmental exposure). Concentrations of 5 μg/dL and 10 μg/dL correspond to the previously permissible PbB concentrations in children or pregnant women, and adults. Our results indicate that even low concentrations of Pb cause an increase in production of inflammatory interleukins (IL-1β and IL-6), increases expression of COX-1 and COX-2, and increases thromboxane B2 and prostaglandin E2 concentration in macrophages. This clearly suggests that the development of inflammation is associated not only with COX-2 but also with COX-1, which, until recently, had only been attributed constitutive expression. It can be concluded that environmental Pb concentrations are able to activate the monocytes/macrophages similarly to the manner observed during inflammation.

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Glycogen metabolism in brain and neurons – astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure

Cited by 20 publications

References 67 publications

Developmental lead (Pb)-induced deficits in hippocampal protein translation at the synapses are ameliorated by ascorbate supplementation

Developmental lead (Pb)-induced deficits in hippocampal protein translation at the synapses are ameliorated by ascorbate supplementation

Pre- and Neonatal Exposure to Lead (Pb) Induces Neuroinflammation in the Forebrain Cortex, Hippocampus and Cerebellum of Rat Pups

Lead (Pb) as a Factor Initiating and Potentiating Inflammation in Human THP-1 Macrophages

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