Sex-Dependent Effects of Developmental Lead Exposure in Wistar Rats: Evidence from Behavioral and Molecular Correlates

Abstract

Lead (Pb) exposure in early life affects brain development resulting in cognitive and behavioral deficits. Epidemiologic and experimental evidence of sex as an effect modifier of developmental Pb exposure is emerging. In the present study, we investigated Pb effects on behavior and mechanisms of neuroplasticity in the hippocampus and potential sex differences. To this aim, dams were exposed, from one month pre-mating to offspring weaning, to Pb via drinking water at 5 mg/kg body weight per day. In the offspring of both sexes, the longitudinal assessment of motor, emotional, and cognitive end points was performed. We also evaluated the expression and synaptic distribution of N-methyl-D-Aspartate receptor (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits at post-natal day (pnd) 23 and 70 in the hippocampus. Neonatal motor patterns and explorative behavior in offspring were affected in both sexes. Pb effects in emotional response and memory retention were observed in adult females only, preceded by increased levels of GluN2A and GluA1 subunits at the post-synapse at pnd 23. These data suggest that Pb exposure during development affects glutamatergic receptors distribution at the post-synaptic spine in females. These effects may contribute to alterations in selected behavioral domains.

Dynamic changes in the hippocampal memory index and biochemical indices in Sprague Dawley rats exposed to intrauterine kola nut

“…The test was conducted in a glass Perspex container of 10 cm in diameter and 10 cm in height, instead of 5 cm in diameter and 10 cm in height, as done by Tartaglione et al (2020), for easy placement and removal of the animals. All other methods were followed.…”

“…The distance traveled by each animal and the mean velocity were recorded. The line crossing, as well as the number of freezing, rearing, and grooming episodes, were also recorded and analyzed with ANY-maze behavioral tracking software (Tartaglione et al, 2020). The presence of fecal bolus and frequency of urination was noted.…”

“…All other methods were followed. Different measurements were conducted within the speculated time of 2 min, based on the methods employed by Tartaglione et al (2020). This includes locomotion, head raising, and pivoting.…”

Available Evidence Indicates That Pediatric Use of Acetaminophen Adversely Affects Neurodevelopment in Susceptible Babies and Children

“…As another potential example, experimental studies of the neurodevelopmental toxicity of "low levels" of lead in rats typically employ blood lead levels of 0.2 ug/ml or more [33,34], but blood lead levels of about 0.1 ug/ml and possibly as low as 0.05 ug/ml are dangerous in humans [30].…”

Endocrine Disrupting Chemicals: Current Understanding, New Testing Strategies and Future Research Needs

“…The projects use an ‘adverse outcome pathway’ (AOP) framework, to develop tests that span molecular initiating events (including in silico predictive models and high throughput screening), key events in in vitro models, and measure adverse outcomes in rodents, zebrafish and humans. Three projects within the EURION focus on improved testing strategies for thyroid hormone disrupting chemicals: ERGO [ 19 ], ATHENA [ 20 ], and SCREENED [ 21 ], while three other projects focus on integrated approaches for the testing and assessment of metabolism disrupting chemicals: OBERON [ 22 ], EDCMET [ 23 ] and GOLIATH [ 24 ]. In addition, the FREIA project develops new tests for effects of EDCs on female reproduction [ 25 ] and the ENDpoiNTs project focusses on developmental neurotoxicity [ 26 ] and methods for elucidating EDC effects.…”