The cognitive impairment induced by zinc deficiency in rats aged 0∼2 months related to BDNF DNA methylation changes in the hippocampus

Hu, Yan-Dan; Pang, Wei; He, Congcong; Lu, Hao; Liu, Wei; Wang, Zhen; Liu, Yanqiang; Huang, Chengyu; Jiang, Yugang

doi:10.1080/1028415x.2016.1194554

Cited by 25 publications

(21 citation statements)

References 34 publications

(29 reference statements)

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“…As previously described [ 34 ], the Morris water maze (MWM) test included four consecutive daily training trials and a probe trial on the fifth day. The test was performed in a circular pool (120 cm in diameter and 60 cm in height) filled with water.…”

Section: Methodsmentioning

confidence: 99%

Galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in mice

Liu

Zhang

Zheng

et al. 2018

J Neuroinflammation

194

105

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BackgroundNeuroinflammation plays an important role in the onset and progression of neurodegenerative diseases such as Alzheimer’s disease. Lipopolysaccharide (LPS, endotoxin) levels are higher in the brains of Alzheimer’s disease patients and are associated with neuroinflammation and cognitive decline, while neural cholinergic signaling controls inflammation. This study aimed to examine the efficacy of galantamine, a clinically approved cholinergic agent, in alleviating LPS-induced neuroinflammation and cognitive decline as well as the associated mechanism.MethodsMice were treated with galantamine (4 mg/kg, intraperitoneal injection) for 14 days prior to LPS exposure (intracerebroventricular injection). Cognitive tests were performed, including the Morris water maze and step-through tests. mRNA expression of the microglial marker (CD11b), astrocytic marker (GFAP), and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) were examined in the hippocampus by quantitative RT-PCR. The inflammatory signaling molecule, nuclear factor-kappa B (NF-κB p65), and synapse-associated proteins (synaptophysin, SYN, and postsynaptic density protein 95, PSD-95) were examined in the hippocampus by western blotting. Furthermore, NF-κB p65 levels in microglial cells and hippocampal neurons were examined in response to LPS and galantamine.ResultsGalantamine treatment prevented LPS-induced deficits in spatial learning and memory as well as memory acquisition of the passive avoidance response. Galantamine decreased the expression of microglia and astrocyte markers (CD11b and GFAP), pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), and NF-κB p65 in the hippocampus of LPS-exposed mice. Furthermore, galantamine ameliorated LPS-induced loss of synapse-associated proteins (SYN and PSD-95) in the hippocampus. In the in vitro study, LPS increased NF-κB p65 levels in microglia (BV-2 cells); the supernatant of LPS-stimulated microglia (Mi-sup), but not LPS, decreased the viability of hippocampal neuronal cells (HT-22 cells) and increased NF-κB p65 levels as well as expression of pro-inflammatory cytokines (IL-1β, IL-6) in HT-22 cells. Importantly, galantamine reduced the inflammatory response not only in the BV-2 microglia cell line, but also in the HT-22 hippocampal neuronal cell line.ConclusionsThese findings indicate that galantamine could be a promising treatment to improve endotoxin-induced cognitive decline and neuroinflammation in neurodegenerative diseases.

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Section: Methodsmentioning

confidence: 99%

Galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in mice

Liu

Zhang

Zheng

et al. 2018

J Neuroinflammation

194

105

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“…33 Also in mice, gestational zinc deficiencies have been linked to epigenetic dysregulation to metallothionein genes (a protein involved in the inactivation and detoxification of metals; a protective mechanism) 34 ; animal work also suggests early life zinc deficiency contributes to increased DNA methylation to BDNF (a stress related gene modulated by the HPA axis), and subsequent cognitive impairment. 35 Taken together, these studies indicate that prenatal neurotoxic metals exposure may contribute to offspring epigenetic alterations indicative of future neurobehavioral morbidity.…”

Section: Introductionmentioning

confidence: 99%

Prenatal exposure to neurotoxic metals is associated with increased placental glucocorticoid receptor DNA methylation

2017

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Epigenetic alterations related to prenatal neurotoxic metals exposure may be key in understanding the origins of cognitive and neurobehavioral problems in children. Placental glucocorticoid receptor (NR3C1) methylation has been linked to neurobehavioral risk in early life, but has not been examined in response to neurotoxic metals exposure despite parallel lines of research showing metals exposure and NR3C1 methylation each contribute to a similar set of neurobehavioral phenotypes. Thus, we conducted a study of prenatal neurotoxic metals exposure and placental NR3C1 methylation in a cohort of healthy term singleton pregnancies from Rhode Island, USA (n D 222). Concentrations of arsenic (As; median 0.02 ug/g), cadmium (Cd; median 0.03 mg/g), lead (Pb; median 0.40 mg/g), manganese (Mn; median 0.56 mg/g), mercury (Hg; median 0.02 mg/g), and zinc (Zn; 145.18 mg/g) measured in infant toenails were categorized as tertiles. Multivariable linear regression models tested the independent associations for each metal with NR3C1 methylation, as well as the cumulative risk of exposure to multiple metals simultaneously. Compared to the lowest exposure tertiles, higher levels of As, Cd, Pb, Mn, and Hg were each associated with increased placental NR3C1 methylation (all P<0.02). Coefficients for these associations corresponded with a 0.71-1.41 percent increase in NR3C1 methylation per tertile increase in metals concentrations. For Zn, the lowest exposure tertile compared with the highest tertile was associated with 1.26 percent increase in NR3C1 methylation (PD0.01). Higher cumulative metal risk scores were marginally associated with greater NR3C1 methylation. Taken together, these results indicate that prenatal exposure to neurotoxic metals may affect the offspring's NR3C1 activity, which may help explain cognitive and neurodevelopmental risk later in life.

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“…Studies on dietary zinc intake showed that high zinc intake could reduce the risk of various cancers [20,39,40], including breast cancer [40]. Previous studies also reported that zinc de ciency in dietary might be associated with increasing level of speci c gene methylation [25,41]. In this study, we rst investigated if dietary zinc intake interacted with DNA methylation to affect the risk of breast cancer.…”

Section: Characteristics Of the Cases And Controlsmentioning

confidence: 99%

“…Zinc de ciency may in uence the function of zinc related genes, including changes the expression of WT1 in zinc de ciency animal model [23], and decreases blood carbonic anhydrase activity in males in a double-blind, randomized crossover study [24]. Hu et al discovered that zinc de ciency increased BDNF methylation level in in vitro experiment [25]. However, studies have yet examined the associations between dietary intake of zinc and zinc related genes, WT1 and CA10, genes methylation in white blood cells with breast cancer risk.…”

Section: Introductionmentioning

confidence: 99%

Joint effects of WT1, CA10 methylation in peripheral blood leukocyte and dietary zinc on breast cancer risk: a case-control study

A¹,

Gao²,

Y³

et al. 2020

Preprint

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Background Studies have shown that abnormal changes of specific-gene DNA methylation in leukocytes may be associated with elevated risk of cancer. However, associations between the methylation of zinc-related genes, WT1 and CA10, and breast cancer risk, and interactions between WT1, CA10 methylation and dietary zinc intake on breast cancer risk remain unknown. Methods The methylation of WT1, CA10 was analyzed by methylation-sensitive high-resolution-melting (MS-HRM) in a case-control study with female subjects (N = 959). Logistic regression was used to analyze the associations and propensity score (PS) method was used to adjust confounders. Results The results showed that WT1 hypermethylation was associated with an increased risk of breast cancer with an odds ratio (OR) of 3.069 [95% confidence interval (CI): 1.669–5.643, P < 0.001]. Subgroup analyses showed that WT1 hypermethylation was specifically associated with an elevated risk of Luminal A subtype (OR = 2.620, 95%CI: 1.107-6.200, P = 0.029) and Luminal B subtype (OR = 3.231, 95%CI: 1.339–7.796, P = 0.009). CA10 hypermethylation was associated with an increased risk of Luminal B subtype (OR = 1.798, 95%CI: 1.085–2.982, P = 0.023). Furthermore, the joint effects of methylation of WT1, CA10 and lower dietary zinc intake were associated a strongly elevated risk of breast cancer with ORs of 11.220 (95%CI: 4.057–31.032, P < 0.001) and 4.145 (95%CI: 2.717–6.324, P < 0.001), respectively. Conclusion The study suggested the hypermethylation of WT1 methylation in leukocytes was significantly associated with an increased risk of breast cancer. Notably, the joint effects of WT1, CA10 methylation and lower dietary zinc intake might significantly associate with breast cancer risk.

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The cognitive impairment induced by zinc deficiency in rats aged 0∼2 months related to BDNF DNA methylation changes in the hippocampus

Cited by 25 publications

References 34 publications

Galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in mice

Galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in mice

Prenatal exposure to neurotoxic metals is associated with increased placental glucocorticoid receptor DNA methylation

Joint effects of WT1, CA10 methylation in peripheral blood leukocyte and dietary zinc on breast cancer risk: a case-control study

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