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Developmental Exposure to Pesticides Alters Motor Activity and Coordination in Rats: Sex Differences and Underlying
B Gómez-Giménez1, V Felipo2, A Cabrera-Pastor1
1Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, Eduardo Primo Yufera, 3, 46012, Valencia, Spain.
Insights
Developmental pesticide exposure impacts children's motor skills, causing sex-specific effects. Neurotransmission changes in the brain explain these alterations, linking pesticide exposure to neurodevelopmental disorders.
Area of Science:
- Environmental toxicology
- Neuroscience
- Developmental toxicology
Background:
- Pesticide exposure during development is linked to neurodevelopmental disorders like ADHD.
- Mechanisms underlying pesticide-induced motor deficits remain unclear.
Purpose of the Study:
- To investigate the effects of four major pesticide classes on motor activity and coordination in developing rats.
- To explore sex-specific neurobiological mechanisms underlying these effects.
Main Methods:
- Rats received daily oral doses of chlorpyrifos, carbaryl, endosulfan, or cypermethrin from gestational day 7 to postnatal day 21.
- Spontaneous motor activity and rotarod performance were assessed in adulthood.
- Extracellular GABA in the cerebellum and NMDA receptor subunits in the hippocampus were analyzed.
Main Results:
- Motor coordination deficits were observed in female rats exposed to endosulfan, cypermethrin, and chlorpyrifos.
- Endosulfan and cypermethrin increased cerebellar GABA levels, particularly in females.
- Chlorpyrifos increased motor activity in both sexes; cypermethrin decreased it mainly in males.
- NR2B NMDA receptor subunit expression in males correlated with motor activity.
Conclusions:
- Developmental exposure to different pesticide classes induces sex-specific motor impairments.
- Alterations in cerebellar GABA and hippocampal NMDA receptor function are implicated.
- These findings enhance understanding of pesticide risks for child neurodevelopment.
Abstract:
It has been proposed that developmental exposure to pesticides contributes to increasing prevalence of neurodevelopmental disorders in children, such as attention deficit with hyperactivity (ADHD) and to alterations in coordination skills. However, the mechanisms involved in these alterations remain unclear. We analyzed the effects on spontaneous motor activity and motor coordination of developmental exposure to a representative pesticide of each one of the four main chemical families: organophosphates (chlorpyrifos), carbamates (carbaryl), organochlorines (endosulfan), and pyrethroids (cypermethrin). Pesticides were administered once a day orally, in a sweet jelly, from gestational day 7 to post natal day 21. Spontaneous motor activity was assessed by an actimeter and motor coordination using the rotarod, when rats were adults. The effects were analyzed separately in males and females. Extracellular GABA in cerebellum and NMDA receptor subunits in hippocampus were assessed as possible underlying mechanisms of motor alterations. Motor coordination was impaired by developmental exposure to endosulfan, cypermethrin, and chlorpyrifos in females but not in males. The effect of endosulfan and cypermethrin would be due to increased extracellular GABA in cerebellum, which remains unaltered in male rats. Chlorpyrifos increased motor activity in males and females. Cypermethrin decreased motor activity mainly in males. In male rats, but not in females, expression of the NR2B subunit of NMDA receptor in hippocampus correlated with motor activity. These results show sex-specific effects of different pesticides on motor activity and coordination, associated with neurotransmission alterations. These data contribute to better understand the relationship between developmental exposure to the main pesticide families and motor disorders in children.
