Effects of low-level organic selenium on lead-induced alterations in neural cell adhesion molecules

doi:10.1016/j.brainres.2013.07.028

Brain Research

Volume 1530, 12 September 2013, Pages 76-81

https://doi.org/10.1016/j.brainres.2013.07.028 Get rights and content

Highlights

•
Se not only prevents but also reverses Pb-induced reductions in NCAMs.
•
Se reduces Pb-induced increases in Pst, Stx and the sialyltransferase activity.
•
Se reduces the blood and hippocampal Pb levels in Pb-exposed rats.

Abstract

Low-level lead (Pb) exposure has been reported to impair the formation and consolidation of learning and memory by inhibiting the expression of neural cell adhesion molecules (NCAMs) and altering the temporal profile of its polysialylation state. In this study, we investigated whether administration of low-level organic selenium (selenomethionine, Se) at different time points could affect Pb-induced changes of NCAMs in female Wistar rats. Here we reported that the exposure of Se (60 μg/kg body weight/day) at different time points significantly alleviated Pb-induced reductions in the mRNA and protein levels of NCAMs, and increases in the mRNA levels of two polysialyltransferases (St8sia II, Stx; St8sia IV, Pst) as well as the sialyltransferase activity (p<0.05). The concentrations of Pb in blood and hippocampi of Wistar rats treated with the combination of Se and Pb were significantly lower than those treated with Pb alone (p<0.05). Our results suggest that low-level organic Se can not only prevent but also reverse Pb-induced alterations in the expression and polysialylated state of NCAMs as well as the concentration of Pb in rat blood and hippocampus.

Introduction

Neural cell adhesion molecules (NCAMs) are involved in morphogenesis, plasticity and regeneration of the nervous system (Minana et al., 2000, Kiss et al., 2001, Ditlevsen et al., 2003). Developmental low-level Pb exposure has been reported to alter the expression of NCAMs and its polysialylation state (i.e. the expression of ST8SiaIV/PST and ST8SiaII/STX, and the activity of sialyltransferase) and therefore may induce the neurotoxicity and the impairment of learning and memory (Fox et al., 1995, Murphy and Regan, 1999, Hu et al., 2008).

Selenium (Se) has been shown to protect against lead-induced neurotoxicity by regulating the uptake and excretion of Pb (Flora et al., 1983), preventing damage from oxygen free radicals (Li et al., 2013, Liu et al., 2013), enhancing the DNA, RNA, protein content, and several enzyme activities such as succinic dehydrogenase, acetylcholinesterase, Na⁺/K⁺ ATPase, and monoamine oxidase (Nehru and Iyer, 1994, Nehru and Dua, 1997, Nehru et al., 1997). However, there is no report of how the treatments of Se at different time points affect the changes of NCAMs induced by Pb, especially the effect of administration of Se after Pb exposure.

There are two kinds of Se: organic and inorganic Se. Organic Se (e.g. SeMet) is easier to get to and much slower to disappear from the central nervous system (CNS) compared to inorganic Se (e.g. sodium selenite) (Gronbaek and Thorlacius-Ussing, 1992). It seems that organic Se may be a much safer and more effective supplement for CNS compared to inorganic Se. Se at low levels is recognized as an essential dietary element for mammalian and for different classes of living organisms, but it is toxic at higher levels (Nogueira and Rocha, 2011). Thus, in this study, we try to investigate the effects of low-level organic Se on the alterations in NCAMs induced by Pb. It was found that low-level organic Se not only prevented but also reversed Pb-induced changes of NCAMs and its polysialylation state in Wistar rats.

Section snippets

Effects of Pb and Se on the expression of NCAMs in rat hippocampus

Three isoforms of NCAMs (NCAM-180, -140 and -120) in the hippocampal homogenates after the removal of polysialic acid by neuraminidase were measured by Western blot assay (Fig. 1A). The Pb exposure alone significantly reduced the expression of NCAM-180, -140 and -120 (p<0.05), compared to the control group, while the Se exposure alone significantly increased the expression of NCAM-140 and NCAM-120 (p<0.05). The pre-, co- or post-treatment of Se significantly increased the expression of all

Discussion

Se was discovered in 1817 and was first found to cause the severe intoxication episodes of livestock in the 1930s and then was determined to be an essential trace element in the diet for mammals (Nogueira and Rocha, 2011). The subsequent intense studies are followed to study the relationship between Se and human diseases (Rayman, 2000, Chiu et al., 2010, Abdulah et al., 2011, Fairweather-Tait et al., 2011, Marti Del Moral et al., 2011, Meplan, 2011). Se has also been found to combat the

Animals and exposure of Pb and Se

Two-month-old specific pathogen free (SPF) female Wistar rats (120–140 g) were purchased from the Animal Facility of Southern Medical University (Guangzhou, China) and used in the present study. They were housed in controlled conditions of 12-h light: 12-h dark cycle, temperature (23 °C), and humidity (60%). Animals had free access to food and water ad libitum. After 1-week normal feeding for accommodation, the female Wistar rats were divided into 6 different groups. During week (W) 2–7, rats

Acknowledgment

This work was supported by grants from National Basic Research Program of China (2012CB525003), the National Natural Science Foundation of China (Nos. 30371198, 30571548 and 81072271) and Key Pioneering Program of Technological Plan in Guangdong Province (2004B33701005).

References (31)

S.T. Chiu et al.
The increase of immunity and disease resistance of the giant freshwater prawn, Macrobrachium rosenbergii by feeding with selenium enriched-diet
Fish Shellfish Immunol.
(2010)
Q. Hu et al.
Maternal low-level lead exposure reduces the expression of PSA-NCAM and the activity of sialyltransferase in the hippocampi of neonatal rat pups
Neurotoxicology
(2008)
Q. Hu et al.
Low-level lead exposure attenuates the expression of three major isoforms of neural cell adhesion molecule
Neurotoxicology
(2011)
J.Z. Kiss et al.
The role of neural cell adhesion molecules in plasticity and repair
Brain Res. Brain Res. Rev.
(2001)
N. Kojima et al.
Biosynthesis and expression of polysialic acid on the neural cell adhesion molecule is predominantly directed by ST8Sia II/STX during in vitro neuronal differentiation
J. Biol. Chem.
(1996)
M.C. Liu et al.
The effect of sodium selenite on lead induced cognitive dysfunction
Neurotoxicology
(2013)
C. Meplan
Trace elements and ageing, a genomic perspective using selenium as an example
J. Trace Elem. Med. Biol.
(2011)
D. Muller et al.
PSA-NCAM is required for activity-induced synaptic plasticity
Neuron
(1996)
P. Plusquellec et al.
The relation of low-level prenatal lead exposure to behavioral indicators of attention in Inuit infants in Arctic Quebec
Neurotoxicol. Teratol.
(2007)
R.G. Pullen et al.
Selenium homeostasis in the central nervous system of the rat
Life Sci.
(1996)

M.P. Rayman

The importance of selenium to human health

Lancet

(2000)

E.P. Scheidegger et al.

A human STX cDNA confers polysialic acid expression in mammalian cells

J. Biol. Chem.

(1995)

R. Abdulah et al.

Molecular targets of selenium in prostate cancer prevention (review)

Int. J. Oncol.

(2011)

W. Birgit et al.

Genetic ablation of polysialic acid causes severe neurodevelopmental defects rescued by deletion of the neural cell adhesion molecule

J. Biol. Chem.

(2005)

C.M. Chuong et al.

Alterations in neural cell adhesion molecules during development of different regions of the nervous system

J. Neurosci.

(1984)

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¹: Both authors contributed equally to this work.

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Research ReportEffects of low-level organic selenium on lead-induced alterations in neural cell adhesion molecules

Highlights

Abstract

Introduction

Section snippets

Effects of Pb and Se on the expression of NCAMs in rat hippocampus

Discussion

Animals and exposure of Pb and Se

Acknowledgment

Fish Shellfish Immunol.

Neurotoxicology

Neurotoxicology

Brain Res. Brain Res. Rev.

J. Biol. Chem.

Neurotoxicology

J. Trace Elem. Med. Biol.

Neuron

Neurotoxicol. Teratol.

Life Sci.

Lancet

J. Biol. Chem.

Molecular targets of selenium in prostate cancer prevention (review)

Int. J. Oncol.

Genetic ablation of polysialic acid causes severe neurodevelopmental defects rescued by deletion of the neural cell adhesion molecule

J. Biol. Chem.

Alterations in neural cell adhesion molecules during development of different regions of the nervous system

J. Neurosci.

Research Report
Effects of low-level organic selenium on lead-induced alterations in neural cell adhesion molecules