Developmental Lead Exposure Induces Depressive-like Behavior in Female Rats

Lisboa, Sabrina F.; Gonçalves, Gisele; Komatsu, Fernanda; Queiroz, Carlos Alfredo Salci; Almeida, Alaor Aparecido; Moreira, Estefânia Gastaldello

doi:10.1081/dct-200039696

Cited by 7 publications

(8 citation statements)

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“…Female rats exposed to Pb through gestation and lactation were more impaired in reference memory than male rats with similar Pb exposures (Jett et al, 1997). De Souza Lisboa et al (2005) reported that exposure to Pb during both pregnancy and lactation led to depressive-like behavior (detected in the forced swimming test) in female but not male rats. The influence of sex as an effect modifier of childhood Pb poisoning has also received little systematic attention.…”

Section: Discussionmentioning

confidence: 99%

Sex and rearing condition modify the effects of perinatal lead exposure on learning and memory

Anderson¹,

Pothakos²,

Schneider³

2012

NeuroToxicology

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Developmental lead (Pb) exposure is associated with cognitive impairments in humans and rodents alike. In particular, impaired spatial learning and memory, as assessed using the Morris water maze (MWM), has been noted in developmentally Pb –exposed rats. Although sex and rearing environment can influence MWM performance in normal animals, the interactions of sex and rearing environment on the impact of developmental Pb exposure on hippocampal-dependent processes has not been well characterized. The present study examined the effects of perinatal exposure (i.e., gestation through weaning) to different levels of Pb (250, 750 and 1,500 ppm Pb acetate in food) in males and females raised in a non-enriched environment (standard cage with 3 animals and no toys) or an enriched environment (large cage containing a variety of toys that were changed twice weekly). Testing in the MWM began at postnatal day 55. Behavioral outcomes were influenced by sex and rearing environment, with complex interactions with Pb exposure. In non-Pb exposed control animals, beneficial effects of environmental enrichment on spatial learning and memory were observed in males and females, with greater effects in females. Pb exposure in females mitigated at least some of the benefits of enrichment on learning, particularly at the lowest and highest exposure levels. In males, enrichment conferred a modest learning advantage and for the most part, Pb exposure did not affect this. However, in males with the highest Pb exposure, enrichment did help to overcome detrimental effects of Pb on learning. In females, any potential benefit to reference memory contributed by enrichment was muted by exposure to Pb and for the most part, this was not reproduced in males. Thus, there are complex interactions between sex, environment, and Pb exposure on spatial learning and memory. Environmental manipulation is a potential risk modifier of developmental Pb exposure and interacts with other factors including sex and amount of Pb exposure to affect the functional influences of Pb on the brain.

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Section: Discussionmentioning

confidence: 99%

Sex and rearing condition modify the effects of perinatal lead exposure on learning and memory

Anderson¹,

Pothakos²,

Schneider³

2012

NeuroToxicology

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“…Other possible mechanisms include direct effects on the hypothalamus ( Bratton et al 1994 ) or pituitary gland ( Huseman et al 1987 ), changes in brain catecholamine levels within the hypothalamus ( Virgolini et al 2005 ), or alterations to cytokine levels ( Hemdan et al 2005 ) and corresponding HPA feedback ( Marx et al 1998 ). Pb exposure could also indirectly affect cortisol levels via changes in body weight ( Scavo et al 1988 ) or nutrition ( Giovannini et al 1990 ) produced by Pb-induced mood changes ( Lisboa et al 2005 ).…”

Section: Discussionmentioning

confidence: 99%

Low-Level Prenatal and Postnatal Blood Lead Exposure and Adrenocortical Responses to Acute Stress in Children

Gump

Stewart

Reihman

et al. 2008

Environ Health Perspect

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BackgroundA few recent studies have demonstrated heightened hypothalamic–pituitary–adrenal (HPA) axis reactivity to acute stress in animals exposed to heavy metal contaminants, particularly lead. However, Pb-induced dysregulation of the HPA axis has not yet been studied in humans.ObjectiveIn this study, we examined children’s cortisol response to acute stress (the glucocorticoid product of HPA activation) in relation to low-level prenatal and postnatal Pb exposure.MethodsChildren’s prenatal blood Pb levels were determined from cord blood specimens, and postnatal lead levels were abstracted from pediatrician and state records. Children’s adrenocortical responses to an acute stressor were measured using assays of salivary cortisol before and after administration of a standard cold pressor task.ResultsPb exposure was not associated with initial salivary cortisol levels. After an acute stressor, however, increasing prenatal and postnatal blood Pb levels were independently associated with significantly heightened salivary cortisol responses.ConclusionsOur results suggest that relatively low prenatal and postnatal blood lead levels—notably those below the 10 μg/dL blood lead level identified by the Centers for Disease Control and Prevention for public health purposes—can alter children’s adrenocortical responses to acute stress. The behavioral and health consequences of this Pb-induced HPA dysregulation in children have yet to be determined.

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“…In spite of its limitations, the oral administration of Pb to the pregnant mother and/or infant is the animal model most frequently used to evaluate the consequences of chronic exposure to low levels of Pb during development. The model allows for behavioral evaluation of the subjects after 70–90 days of exposure and age (de Souza Lisboa et al, 2005 ; Weston et al, 2014 ). Additionally, this scheme of exposure enables the evaluation of epigenetic effects (DNA methylation, histone modifications, and ncRNAs regulation) induced by exposure to Pb.…”

Section: How To Address the Problem Of Neurological Alterations Due Tmentioning

confidence: 99%

A Hypothesis of the Interaction of the Nitrergic and Serotonergic Systems in Aggressive Behavior Induced by Exposure to Lead

Martínez-Lazcano

López-Quiroz

Alcantar-Almaraz

et al. 2018

Front. Behav. Neurosci.

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The effects caused by exposure to lead (Pb) are still considered as a relevant health risk despite public policies aimed to restricting the use of this element. The toxicity limit in the blood (10 μg/dL, established by the Center for Disease Control and Prevention) has been insufficient to prevent adverse effects and even lower values have been related to neurobehavioral dysfunctions in children. Currently, there is not a safe limit of exposure to Pb. A large body of evidence points to environmental pollutant exposure as the cause of predisposition to violent behavior, among others. Considering the evidence by our group and others, we propose that Pb exposure induces alterations in the brain vasculature, specifically in nitric oxide synthases (NOS), affecting in turn the serotonergic system and leading to heightened aggressive behavior in the exposed individuals. This review article describes the consequences of Pb exposure on the nitrergic and serotonergic systems as well as its relationship with aggressive behavior. In addition, it summarizes the available therapy to prevent damage in gestation and among infants.

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Developmental Lead Exposure Induces Depressive-like Behavior in Female Rats

Cited by 7 publications

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Sex and rearing condition modify the effects of perinatal lead exposure on learning and memory

Sex and rearing condition modify the effects of perinatal lead exposure on learning and memory

Low-Level Prenatal and Postnatal Blood Lead Exposure and Adrenocortical Responses to Acute Stress in Children

A Hypothesis of the Interaction of the Nitrergic and Serotonergic Systems in Aggressive Behavior Induced by Exposure to Lead

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