Age related changes in aminergic system and behavior following lead exposure: Protection with essential metal supplements
Introduction
Recent studies suggested that exposure to environmental toxic agents during early life has been linked to neurodegenerative diseases and deficits in cognitive and motor functions in later life (Landrigan et al., 2005, Basha et al., 2005, Lahiri et al., 2008, Weuve et al., 2009). Lead (Pb) is a pervasive and persistent environmental toxic metal and the adverse health effects of Pb have been known for centuries (Zbakh and El Abbassi, 2012). Exposure to Pb at any age can be harmful and has shown demonstrable effects including neurological (Reddy et al., 2003), cardiac (Basha et al., 2012a, Basha et al., 2012b), hepatic (Patra et al., 2001), behavioral (Prasanthi et al., 2006), renal and hematological dysfunctions (Rastogi, 2008). Several experimental and epidemiological studies suggest that the neurotoxic effects of Pb are mediated through interference with the cholinergic and aminergic systems (Xu et al., 2009, El-Ansary et al., 2011). Oxidative stress has been proposed to be another mechanism involved in Pb toxicity (Franco et al., 2009, Dewanjee et al., 2013). Our earlier studies showed that the gestational and/or lactational exposure to Pb perturbs the cholinergic, aminergic and antioxidant systems in different brain regions of developing rats even though blood Pb (PbB) levels have declined (Devi et al., 2005, Basha et al., 2005, Verina et al., 2007, Reddy et al., 2007, Prasanthi et al., 2010, Basha et al., 2012a, Basha et al., 2012b). Bolin et al. (2006) also reported that Pb exposure during development have shown a continuation of neurological deficits that remain well into adult hood when blood levels are undetectable. The behavioral abnormalities, particularly those associated with the cognitive and motor functions, normally manifested in Pb-exposed rats have been attributed to the toxic effects of Pb on cholinergic and aminergic transmission (De la Fuente et al., 2003, Verina et al., 2007). Therefore, in the present study, we wanted to examine whether early exposure to Pb can manifest latent effects in old age and such effects can be reversed with essential elements calcium, zinc, and iron. Nutritional status is often mentioned as an important modifier of the metabolism of Pb toxicity (Ahamed and Siddiqui, 2007). Low dietary intake of iron, zinc, calcium has been associated with increased blood Pb levels and neurotoxicity of Pb (Prasanthi et al., 2010). We have previously reported that calcium and zinc supplementation significantly reversed the Pb-induced perturbations in mitochondrial antioxidant enzymes, and neurotransmitter levels in different brain regions of rats (Prasanthi et al., 2005, Basha et al., 2012a, Basha et al., 2012b). In the present study, we examined the therapeutic efficacy of nutritional supplement containing a mixture of essential elements calcium, zinc and iron against Pb-induced alterations in brain aminergic transmitter system and behavior.
Section snippets
Chemicals
Chemicals (imidazole, heptane, cysteine, O-pthaladehyde, tyramine hydrochloride) used in this study were purchased from Sigma Chemicals (St. Louis, MO, USA) and all the remaining chemicals were from Merck, India.
Animal exposure
Pregnant rats were lactationally exposed to 0.2% Pb by adding Pb-acetate to deionized drinking water of the mother. All pups were pooled on postnatal day 1 (PND 1) and new litters consisting of eight males were randomly selected and placed with each dam. Pb-exposure commenced on PND 1,
Results
The specific activity of the mitochondrial MAO enzyme and synaptosomal catecholamines (dopamine, epinephrine, norepinephrine and serotonin) were determined in cerebral cortex, hippocampus and cerebellum at PND 45, 4 months, 12 months and 18 months of control, Pb-exposed and nutrient mixture supplemented rats (Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5). As shown in Fig. 1, Fig. 2, Fig. 3, Fig. 4, in control rats, the catecholamine levels in general increased from early postnatal age (PND 45) to 12
Discussion
In the present study, we observed significant and brain region specific alterations in the synaptosomal dopamine, epinephrine, norephinephrine and serotonin levels as well as mitochondrial MAO activity in Pb-exposed rats. To date, numbers of studies have addressed the effects of Pb on cholinergic and aminergic systems and behavior in developing rats (Van Wijngaarden et al., 2009, Mansouri et al., 2013), but the present study focused on long term effects of Pb on behavior and aminergic system of
Acknowledgement
This research work was supported by Indian Council of Medical Research (ICMR) Grant No. 5/8/4-10(Env)/09-NCD-I.
References (54)
- et al.
Environmental lead toxicity and nutritional factors
Clin. Nutr.
(2007) - et al.
Development and plasticity of the hippocampal-cholinergic system in normal and early lead-exposed rats
Brain Res.
(1983) - et al.
A rapid and sensitive procedure for the combined assay of noradrenaline, dopamine and serotonin in a single brain sample
Anal. Biochem.
(1968) - et al.
Perinatal lead exposure alters postnatal cholinergic and aminergic system in rat brain: reversal effect of calcium co-administration
Int. J. Dev. Neurosci.
(2012) - et al.
Effects of chronic administration of melatonin on spatial learning ability and long-term potentiation in lead-exposed and control rats
Biomed. Environ. Sci.
(2009) - et al.
Synaptic plasma membranes from rat brain synaptosomes: isolation and partial characterization
Biochem. Biophys. Acta
(1971) - et al.
Characterization of monoaminergic systems in brain regions of prematurely ageing mice
Neurochem. Int.
(2003) - et al.
Developmental lead exposure alters mitochondrial monoamine oxidase and synaptosomal catecholamine levels in rat brain
Int. J. Dev. Neurosci.
(2005) - et al.
Toxic effects of lead exposure in Wistar rats: involvement of oxidative stress and the beneficial role of edible jute (Corchorus olitorius) leaves
Food Chem. Toxicol.
(2013) - et al.
Relationship between chronic lead toxicity and plasma neurotransmitters in autistic patients from Saudi Arabia
Clin. Biochem.
(2011)
Dietary calcium supplementation to lower blood lead levels in pregnancy and lactation
J. Nutr. Biochem.
The relationship between lead exposure, motor function and behaviour in Inuit preschool children
Neurotoxicol. Teratol.
The biological chemistry of lead
Curr. Opin. Chem. Biol.
Developmental lead exposure impairs contextual fear conditioning and reduces adult hippocampal neurogenesis in the rat brain
Int. J. Dev. Neurosci.
Protein measurement with Folin phenol reagent
J. Biol. Chem.
Postnatal lead exposure affects motor skills and exploratory behavior in rats
Environ. Res.
Motor alterations induced by chronic lead exposure
Environ. Toxicol. Pharmacol.
Behavioral deficits induced by lead exposure are accompanied by serotonergic and cholinergic alterations in the prefrontal cortex
Neurochem. Int.
Differential effect of post-training naloxone, beta-endorphin, leu-enkephalin and electroconvulsive shock administration upon memory of an open-field habituation and of a water-finding task
Psychoneuroendocrinology
Antioxidant effects of alpha tocopherol, ascorbic acid and l-methionine on lead-induced oxidative stress to the liver, kidney and brain in rats
Toxicology
Relatons of bone and blood lead to cognitive function: The VA normative aging study
Neurotoxicol. Teratol.
Calcium and zinc supplementation protects lead (Pb)-induced perturbations in antioxidant enzymes and lipid peroxidation in developing mouse brain
Int. J. Devlop. Neurosci.
Calcium and zinc supplementation reduces lead toxicity: assessment of behavioral dysfunctions in young and adult mice
Nutr. Res.
Lead-induced effects on Acetylcholinesterase activity in cerebellum and hippocampus of developing rat brain
Int. J. Devlop. Neurosci.
Developmental lead neurotoxicity: alterations in brain cholinergic system
NeuroToxicology
Changes in tissue responsiveness to hormones and neurotransmitters during aging
Exp. Gerontol.
Bone lead levels are associated with measures of memory impairment in older adults
Neurotoxicology
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