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Published on: November 20, 2015
Perinatal exposure to polychlorinated biphenyls differentially affects cerebellar development and motor functions in
K Nguon1, M G Baxter, E M Sajdel-Sulkowska
1Department of Psychiatry, Brigham & Women's Hospital, Boston, MA, USA.
Insights
Perinatal exposure to polychlorinated biphenyls (PCBs) impairs neurodevelopment and motor function in rats, with males showing greater deficits. PCB exposure alters cerebellar structure and protein expression, suggesting sex-specific impacts on the central nervous system (CNS).
Area of Science:
- Neuroscience
- Developmental Biology
- Environmental Toxicology
Background:
- Perinatal exposure to polychlorinated biphenyls (PCBs) is known to interact with genetics, affecting central nervous system (CNS) development.
- Previous studies indicate potential neurobehavioral impairments, including motor dysfunction, following PCB exposure.
- The cerebellum is a critical brain region for motor control and development, making it a key area of investigation.
Purpose of the Study:
- To test the hypothesis that neurobehavioral impairments and motor dysfunctions from perinatal PCB exposure are linked to cerebellar changes.
- To compare neurodevelopment, motor behavior, cerebellar structure, and protein expression in PCB-exposed and control rat neonates.
- To investigate potential sex-specific differences in the effects of PCB exposure on the developing brain and behavior.
Main Methods:
- Rat neonates were exposed to the PCB mixture Aroclor 1254 (A1254) from gestational day 11 to postnatal day 21.
- Neurodevelopmental milestones (e.g., ear unfolding), motor behaviors (e.g., righting response, negative geotaxis, rotorod), and cerebellar structure were assessed.
- Cerebellar protein expression (GFAP, L1) was analyzed using Western blotting or similar techniques.
Main Results:
- A1254 exposure led to reduced body mass between birth and weaning, with greater differences in females by P21.
- PCB exposure delayed ear unfolding and impaired motor function across multiple tests, with male pups exhibiting more severe deficits.
- Cerebellar mass was reduced, particularly in males. GFAP expression increased (greater in males), and L1 expression decreased in both sexes.
Conclusions:
- Perinatal PCB exposure significantly impacts neurodevelopment and motor behavior in rats, with notable sex-specific differences.
- Observed behavioral changes are associated with structural and molecular alterations in the cerebellum, suggesting its role in PCB-induced neurotoxicity.
- These findings highlight the potential for environmental pollutants like PCBs to contribute to sex-related disparities in neuropsychiatric disorders.
Abstract:
Perinatal exposure to polychlorinated biphenyls (PCBs) interacts with genetics and impacts the course of the central nervous system (CNS) development in both humans and animals. To test the hypothesis that the neurobehavioral impairments, and specifically motor dysfunctions following perinatal PCB exposure in rats are associated with changes in a specific brain region, the cerebellum, we compared neurodevelopment, motor behavior, cerebellar structure, and protein expression in rat neonates exposed to the PCB mixture Aroclor 1254 (A1254, 10.0 mg/kg/day) from gestational day 11 until postnatal day (P) 21 with that of controls. Body mass of PCB-exposed pups was not affected at birth, but was significantly lower than that of controls between birth and weaning; by P21 the difference was greater in females than in males. A1254 exposure delayed ear unfolding and impaired performance on the following behavioral tests: (1) righting response on P3-P6; (2) negative geotaxis on P5-P7; (3) startle response on P10-P12; and (4) a rotorod on P12, with PCB-male pups more severely affected than female. Changes in the behavior of PCB pups were associated with changes in cerebellar structure and protein expression. Cerebellar mass was more reduced in PCB-male than PCB-female pups. Analysis of selected cerebellar proteins revealed an increase in GFAP expression, greater in male than in female, and a decrease in L1 expression in both sexes. These results suggest that PCB exposure affects behavior and cerebellar development differently in male and female rat neonates, with greater effects in males. Further studies of neonatal PCB exposure will establish whether the environmental pollutants can contribute to the sex-related preponderance of certain neuropsychiatric disorders.
