Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Cumulative Exposure to Multiple Early Life Stressors Act as Risk Factors for Neurodevelopmental Abnormalities in the F1 Wistar Rats

Version 1 : Received: 11 July 2023 / Approved: 11 July 2023 / Online: 12 July 2023 (05:21:26 CEST)

A peer-reviewed article of this Preprint also exists.

Mujtaba, S.; Patro, I.K.; Patro, N. Multiple Early Life Stressors as Risk Factors for Neurodevelopmental Abnormalities in the F1 Wistar Rats. Brain Sci. 2023, 13, 1360. Mujtaba, S.; Patro, I.K.; Patro, N. Multiple Early Life Stressors as Risk Factors for Neurodevelopmental Abnormalities in the F1 Wistar Rats. Brain Sci. 2023, 13, 1360.

Abstract

Cumulative exposure to multiple early life stressors are expected to affect behavioral development causing increased susceptibility towards neuropsychiatric disorders. The present study was designed to mimic such conditions in rat model to study behavioral impairments during adolescence and adulthood. Female Wistar rats (n=32; 140-150 gm) were switched to low protein (LP; 8% protein) or Control (20% protein) diet, 15 days prior to conception and then diet regime was maintained throughout the experimental period. Pups born to Control and LP dams were intraperitoneally injected with deltamethrin (DLT-pyrethroid insecticide; 0.7mg/kg body weight; PND 1 to 7) or lipopolysaccharide (LPS-bacterial endotoxin; 0.3mg/kg body weight; PND 3 and 5) or DLT+LPS, on designated days forming 8 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 more susceptible to either singular or cumulative exposure as compared to their age matched control counterparts, showing significantly severe behavioural abnormalities, as hyperactivity, attention deficits, impulsiveness 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; Impulsiveness; Schizophrenia; ADHD

Subject

Biology and Life Sciences, Neuroscience and Neurology

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