Multiple Early Life Stressors as Risk Factors for Neurodevelopmental Abnormalities in the F1 Wistar Rats

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.

Keywords

• multi-hit stress
• protein malnourishment
• low anxiety
• hyperactivity
• schizophrenia
• ADHD