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Multiple Early Life Stressors as Risk Factors for Neurodevelopmental Abnormalities in the F1 Wistar Rats
Syed Mujtaba1,2, Ishan Kumar Patro1,2, Nisha Patro1
1School of Studies in Neuroscience, Jiwaji University, Gwalior 474011, India.
Insights
Early life exposure to low protein diets and environmental toxins like deltamethrin (DLT) and lipopolysaccharide (LPS) significantly increases susceptibility to behavioral abnormalities. These findings suggest a predisposition to neurodevelopmental disorders such as schizophrenia and ADHD.
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Early life stress is linked to increased risk of neuropsychiatric disorders.
- Animal models are crucial for understanding the long-term effects of early life exposures on behavior.
Purpose of the Study:
- To investigate the impact of cumulative early life stressors, including a low protein (LP) diet and exposure to deltamethrin (DLT) and lipopolysaccharide (LPS), on behavioral development in a rat model.
- To assess neurobehavioral impairments during adolescence and adulthood.
Main Methods:
- Female Wistar rats were fed either a control (20% protein) or LP (8% protein) diet pre-conception and throughout gestation/lactation.
- Pups were exposed to DLT (insecticide), LPS (bacterial endotoxin), or both, during the postnatal period (PND 1-7).
- Neurobehavioral assessments (open field, elevated plus maze, light/dark box, rotarod) were conducted at 1, 3, and 6 months of age.
Main Results:
- Rats exposed to LP diets showed heightened susceptibility to singular or combined DLT and LPS exposures.
- Significant behavioral abnormalities, including hyperactivity, attention deficits, and reduced anxiety, were observed in LP-exposed rats.
- These behavioral changes mimic symptoms associated with neuropsychiatric disorders like schizophrenia and ADHD.
Conclusions:
- Cumulative early life exposure to nutritional deficits and environmental toxins can lead to significant and lasting behavioral impairments.
- This multi-hit model suggests a potential mechanism predisposing individuals to developmental disorders.
- Early life interventions may be critical for mitigating the long-term consequences of such exposures.
Abstract:
Cumulative exposure to multiple early life stressors is expected to affect behavioral development, causing increased susceptibility to neuropsychiatric disorders. The present study was designed to mimic such conditions in a rat model to study behavioral impairments during adolescence and adulthood. Female Wistar rats (n = 32; 140-150 gm) were switched to a low protein (LP; 8% protein) or control (20% protein) diet 15 days prior to conception, and then the diet regime was maintained throughout the experimental period. Pups born to control and LP dams were intraperitoneally injected with deltamethrin (DLT-pyrethroid insecticide; 0.7 mg/kg body weight; PND 1 to 7), lipopolysaccharide (LPS-bacterial endotoxin; 0.3 mg/kg body weight; PND 3 and 5), or DLT+LPS, on designated days forming eight experimental groups (Control, LP, Control+LPS, LP+LPS, Control+DLT, LP+DLT, Control+DLT+LPS and LP+DLT+LPS). Neurobehavioral assessments were performed in F1 rats (1, 3, 6 months) by open field, elevated plus maze, light and dark box, and rotarod tests. LP rats were found to be highly susceptible to either singular or cumulative exposure as compared to their age-matched control counterparts, showing significantly severe behavioral abnormalities, such as hyperactivity, attention deficits and low anxiety, the hallmark symptoms of neuropsychiatric disorders like schizophrenia and ADHD, suggesting thereby that early life multi-hit exposure may predispose individuals to developmental disorders.
