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Prenatal exposure to lambda-cyhalothrin alters brain dopaminergic signaling in developing rats
Yogesh K Dhuriya1, Pranay Srivastava2, Rajendra K Shukla2
1Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow - 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Lucknow Campus, India.
Prenatal exposure to lambda-cyhalothrin (LCT) selectively alters dopamine D2 receptors and related signaling proteins in developing rat brains. These changes may impair spontaneous motor activity, highlighting neurodevelopmental risks of pyrethroid pesticides.
Area of Science:
- Neuroscience
- Toxicology
- Developmental Biology
Background:
- Synthetic pyrethroids, like lambda-cyhalothrin (LCT), are widely used insecticides.
- Prenatal exposure to environmental toxins can disrupt neurodevelopment.
- Dopaminergic signaling in the corpus striatum is crucial for motor control.
Purpose of the Study:
- To investigate the molecular mechanisms of dopaminergic alterations in the corpus striatum of rats exposed prenatally to lambda-cyhalothrin (LCT).
- To assess the impact of LCT exposure on dopamine receptor expression and associated signaling pathways during development.
Main Methods:
- Developing rats were exposed prenatally to varying doses of LCT (0.5, 1, and 3 mg/kg body weight).
- mRNA and protein expression levels of dopamine receptors (D1, D2), tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), DARPP-32, pCREB, and PP1α were analyzed.
- Dopamine D2 receptor binding was assessed using 3H-Spiperone.
Main Results:
- Prenatal LCT exposure (1 and 3 mg/kg) decreased DA-D2 receptor mRNA and protein levels, and D2 receptor binding on postnatal day 22 (PD22).
- Expression of TH, DAT, VMAT2, DARPP-32, and pCREB decreased, while PP1α increased, following LCT exposure (1 and 3 mg/kg) on PD22.
- A trend towards recovery was observed at a moderate LCT dose (1.0 mg/kg) by PD45, while high-dose effects persisted; low-dose LCT showed no significant changes.
Conclusions:
- Dopaminergic signaling alterations following LCT exposure are primarily due to selective changes in DA-D2 receptors in the corpus striatum.
- These neurochemical changes may underlie the observed impairment in spontaneous motor activity.
- The findings suggest potential neurodevelopmental risks associated with prenatal exposure to lambda-cyhalothrin.
