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

• Published in: International journal of molecular sciences 2020-04, Vol.21 (8), p.2664
• Main Authors: Tartaglione, Anna Maria, Serafini, Melania Maria, Raggi, Andrea, Iacoponi, Francesca, Zianni, Elisa, Scalfari, Alessandro, Minghetti, Luisa, Ricceri, Laura, Cubadda, Francesco, Calamandrei, Gemma, Viviani, Barbara
• Format: Article
• Language: English
• Subjects: Adults; Animal cognition; Animals; Behavior; Behavior, Animal; Behavioral plasticity; Body weight; Brain - metabolism; Child development; Developmental Disabilities - diagnosis; Developmental Disabilities - etiology; Developmental plasticity; Disease Models, Animal; Disease Susceptibility; Drinking water; Emotional factors; Emotions; Environmental Exposure - adverse effects; Epidemiology; Exploratory behavior; Exposure; Female; glutamatergic receptors; Glutamatergic transmission; Glutamic acid receptors (ionotropic); Hippocampus; Hippocampus - metabolism; lead; Lead - adverse effects; Lead - blood; Lead - metabolism; Male; Mental Disorders - diagnosis; Mental Disorders - etiology; N-Methyl-D-aspartic acid receptors; Neonates; neurodevelopment; Neuronal Plasticity - drug effects; Neuroplasticity; Neurotoxicity; Rats; Receptors, Glutamate - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; Sex Characteristics; Sex differences; Sexes; sexual dimorphism; Studies; Synapses; Synaptic plasticity; Weaning; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21082664

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.