Sex-Dependent Effects of Developmental Lead Exposure in Wistar Rats: Evidence from Behavioral and Molecular Correlates
Open Access
- 11 April 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (8), 2664
- https://doi.org/10.3390/ijms21082664
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.Funding Information
- Joint Programming Initiative A healthy diet for a healthy life (2015/17/Z/NZ7/04273)
This publication has 93 references indexed in Scilit:
- GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunctionNature Genetics, 2013
- Differential Effect of Postnatal Lead Exposure on Gene Expression in the Hippocampus and Frontal CortexJournal of Molecular Neuroscience, 2011
- Hippocampal GluR1 associates with behavior in the elevated plus maze and shows sex differencesBehavioural Brain Research, 2011
- Distinct Modes of AMPA Receptor Suppression at Developing Synapses by GluN2A and GluN2B: Single-Cell NMDA Receptor Subunit Deletion In VivoNeuron, 2011
- Lead exposure during synaptogenesis alters NMDA receptor targeting via NMDA receptor inhibitionNeuroToxicology, 2011
- NMDA receptor subunit composition controls synaptogenesis and synapse stabilizationProceedings of the National Academy of Sciences of the United States of America, 2011
- Molecular Neurobiology of Lead (Pb2+): Effects on Synaptic FunctionMolecular Neurobiology, 2010
- Glutamate Receptor Ion Channels: Structure, Regulation, and FunctionPharmacological Reviews, 2010
- Allosteric modulators of NR2B‐containing NMDA receptors: molecular mechanisms and therapeutic potentialBritish Journal of Pharmacology, 2009
- Low-Level Human Equivalent Gestational Lead Exposure Produces Sex-Specific Motor and Coordination Abnormalities and Late-Onset Obesity in Year-Old MiceEnvironmental Health Perspectives, 2008