From the Cover: Arsenic Induces Hippocampal Neuronal Apoptosis and Cognitive Impairments via an Up-Regulated BMP2/Smad-Dependent Reduced BDNF/TrkB Signaling in Rats

Pandey, Rukmani; Rai, Vipin; Mishra, Juhi; Mandrah, Kapil; Roy, Somendu Kumar; Bandyopadhyay, Sanghamitra

doi:10.1093/toxsci/kfx124

Cited by 55 publications

(29 citation statements)

References 92 publications

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“…Another study proved that As can reduce mitochondira membrane potential (MMP) and decrease BDNF gene expression in As treated human neuroblastoma SH-SY 5 Y cells [42]. As induces hippocampal neuronal apoptosis through an up regulated none morphogenic protein 2 (BMP2), Smad dependent attenuation of BDNF TrkB pathway resulting cognitive impairments [43]. Moreover, it was also found that subchronic As exposure in chemically depression induced mouse model enhances the depression-like behaviors through the cerebral prefrontal cortex BDNF-TrkB signaling pathway [44].…”

Section: Discussionmentioning

confidence: 99%

Blood heavy metals and brain-derived neurotrophic factor in the first trimester of pregnancy among migrant workers

Zaw

Taneepanichskul

2019

PLoS ONE

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Background Lead, mercury, cadmium and arsenic are the priority heavy metals of major public health concern in industrialized countries. Exposure to them can cause cognitive impairment and depressive disorders through an effect on Brain-derived neurotrophic factor (BDNF) which is an important biomarker of pregnancy. Despite a number of prior studies on heavy metals pollution, there is few of studies on the effect of heavy metals on BDNF during early pregnancy. This study aims to examine the association between maternal blood heavy metals concentrations and BDNF during the first trimester pregnancy among Myanmar migrants in Thailand. Methodology This cross sectional study, a part of ongoing birth cohort was conducted at the antenatal care clinic from June to October 2018. A total of 108 with Myanmar migrant pregnancy with a single viable fetus of 0 to 14 gestation weeks who stayed within the industrial plant at least 3 months before were recruited. Socio-demographic characteristics and health behaviors were accessed using a self-report questionnaire. Maternal blood heavy metals (lead (Pb), mercury (Hg), cadmium (Cd) and arsenic (As)) were measured using an inductively coupled plasma mass spectrometer and plasma BDNF was measured using an enzyme-linked immunosorbent assay. Multivariate binary logistic regression were modeled to access the association. Results Median (interquartile rank: IQR) concentrations were: BDNF (6.49 (1.79) μg/ml), Pb (2.77 (1.46) μg/dL), Hg (0.62 (0.54) μg/dL), Cd (0.93(0.86) μg/L) and As (0.40 (0.11) μg/dL) respectively. We categorized BDNF concentrations into high (> median) (n = 54) and low (≤ median) (n = 54) groups. After adjusting for potential confounders, high blood total arsenic concentration had 2.6-fold increased odds (aOR = 2.603, 95% CI: 1.178, 5.751) of low plasma BDNF level as compared with low blood total arsenic group. However, there was no significant association between BDNF and Pb, Hg and Cd. Conclusions The present findings demonstrate higher blood total arsenic level were more likely to have lower BDNF in early pregnancy. Our study suggested that heavy metal could be worsen BDNF level which plays its important role on biological effect of maternal depressive disorder and newborn neurodevelopment.

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Section: Discussionmentioning

confidence: 99%

Blood heavy metals and brain-derived neurotrophic factor in the first trimester of pregnancy among migrant workers

Zaw

Taneepanichskul

2019

PLoS ONE

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“…Cryosections of the cerebral cortex from HFD‐fed mice were incubated with fluorescein‐labeled dUTP and TdT (9 : 1) (overnight) and GFAP or β‐tubulin III antibodies and co‐stained with nuclear Hoechst, following the process described earlier (Pandey et al . ). The sections were then photomicrographed under fluorescent microscope and apoptotic index expressed as the number of TUNEL‐positive cells/100 nuclei in GFAP‐expressing astrocytes or β‐tubulin III‐expressing neurons.…”

Section: Methodsmentioning

confidence: 97%

Rosiglitazone up‐regulates glial fibrillary acidic protein via HB‐EGF secreted from astrocytes and neurons through PPARγ pathway and reduces apoptosis in high‐fat diet‐fed mice

Kushwaha

Mishra

Gupta

et al. 2018

Journal of Neurochemistry

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The anti-diabetic drug and peroxisome proliferator-activated receptor-gamma (PPARc) agonist, rosiglitazone, alters astrocyte activation; however, its mechanism remains less-known. We hypothesized participation of epidermal growth factor receptor (EGFR), known to control astrocyte reactivity. We first detected that rosiglitazone promoted glial fibrillary acidic protein (GFAP) expression in primary astrocytes as well as the mouse cerebral cortex, associated with increased EGFR activation. Screening for EGFR ligands revealed a rosiglitazone-mediated increase of heparin-binding epidermal growth factor (HB-EGF) in astrocytes, resulting in HB-EGF release into culture medium and mouse cerebrospinal fluid too. Treatment with HB-EGF-siRNA and EGFR inhibitors showed that the rosiglitazone-induced HB-EGF and p-EFGR were interdependent, which participated in GFAP increase. Interestingly, we observed that rosiglitazone could induce cellular and secreted-HB-EGF in neurons also, contributing toward the activated EGFR-induced GFAP in astrocytes. Probing whether these effects of rosiglitazone were PPARc-linked, revealed potential PPARc-responsive elements within HB-EGF gene. Moreover, gel-shift, site-directed mutagenesis, chromatinimmunoprecipitation and luciferase-reporter assays demonstrated a PPARc-dependent HB-EGF transactivation. Subsequently, we examined effects of rosiglitazone in a high-fat diet-fed diabetes mouse model, and supporting observations in the normal cortical cells, identified a rosiglitazone-induced GFAP, astrocyte and neuronal HB-EGF and secreted-HB-EGF in the cerebral cortex of diabetic mice. Moreover, assessing relevance of increased HB-EGF and GFAP revealed an anti-apoptotic role of rosiglitazone in the cerebral cortex, supported by a GFAP-siRNA as well as HB-EGF-siRNA-mediated increase in cleaved-caspase 3 and 9 levels in the rosiglitazone-treated astrocyte-neuron coculture. Overall, our study indicates that rosiglitazone may protect the brain, via a PPARc-dependent HB-EGF/EGFR signaling and increased GFAP.

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“…Fas/FasL pathway further exacerbated the condition of colitis mice. Studies have shown that the TrkB-PLC/IP3 pathway can inhibit anxiety-and depression-like behaviors, mainly by inhibiting the apoptosis of hippocampal neurons [33][34][35]. In this study, we did not explore the specific mechanism of TrkB-PLC/IP3 pathway on inflammation and apoptosis, and its application in clinical treatment remained to be further studied.…”

Section: Discussionmentioning

confidence: 91%

Effect of TrkB-PLC/IP3 pathway on intestinal inflammatory factors and enterocyte apoptosis in mice with colitis

Sun

et al. 2020

Preprint

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Background This study aimed to explore the effect of TrkB-PLC/IP3 pathway on intestinal inflammatory factors and enterocyte apoptosis in mice with colitis.Methods Forty 8-week SPF C57BL/6J mice were randomly and averagely divided into normal group (healthy mice), control group (sham-operated mice), model group (model mice without any treatment), and K252a group (model mice with the treatment of 100 μmoL/kg TrkB-PLC/IP3 pathway inhibitor for 5 d before clysis). Mice in model and K252a groups were used to establish ulcerative colitis models after medication.Results There were no significant changes of the content of serum tumor necrosis factor-α (TNF-α) and TNF-γ and protein expressions of TNF-α and TNF-γ in the colon tissues (all P >0.05), a significant increase of disease activity index, colon mucosa damage index, tissue damage index scores, content and protein expressions of serum interleukin-4 (IL-4) and IL-8, and a significant decrease of content and protein expressions of serum IL-10 (all P <0.05) in model and K252a groups, as compared to normal and control groups. Mice in model and K252a groups had blocked enterocyte cycle progression, raised apoptosis ratio, significantly increased mRNA and protein expressions of Caspase3, Bax, FasL and Fas, and significantly reduced mRNA and protein expressions of p-TrkB, PLC-γ1, IP3 and Bcl-2 (all P <0.05). Moreover, intestinal inflammation and apoptosis induced by colitis in K252a group became more aggravated through the inhibition of TrkB-PLC/IP3 pathway activity.Conclusions Inhibition of TrkB-PLC/IP3 pathway can promote the expression of intestinal inflammatory factors and enterocyte apoptosis in mice with colitis.

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From the Cover: Arsenic Induces Hippocampal Neuronal Apoptosis and Cognitive Impairments via an Up-Regulated BMP2/Smad-Dependent Reduced BDNF/TrkB Signaling in Rats

Cited by 55 publications

References 92 publications

Blood heavy metals and brain-derived neurotrophic factor in the first trimester of pregnancy among migrant workers

Blood heavy metals and brain-derived neurotrophic factor in the first trimester of pregnancy among migrant workers

Rosiglitazone up‐regulates glial fibrillary acidic protein via HB‐EGF secreted from astrocytes and neurons through PPARγ pathway and reduces apoptosis in high‐fat diet‐fed mice

Effect of TrkB-PLC/IP3 pathway on intestinal inflammatory factors and enterocyte apoptosis in mice with colitis

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