The Effects of Developmental Lead Exposure in the Rat on Brain Excitability Through in-vivo Seizure Susceptibility

Abstract

Developmental lead poisoning in the rat model has been shown to alter the influence that the GABAergic inhibitory system has in balancing brain excitability across the lifespan. The results of disrupted inhibitory systems in early development are associated with later life behavioral and cognitive impulsivity and poor decision making, increased agitation and emotional dysregulation, and learning and memory problems. The present study sought to investigate the effects of perinatal lead exposure at 150 ppm and 1,000 ppm (via drinking water), when i compared to Control {non-lead exposed rats), an adult (postnatal day 55-70) Long Evans Hood Rats seizure susceptibility when challenged by the Glutamatergic agonist Kainic Acid (5mg/kg s.c.). In-vivo neurosurgeries were conducted under Ketamine (91mg/kg) and Xylazine (9.1mg/kg) anesthesia cocktails (i.p.) for 90 minutes. During the first 15 minutes, baseline brain activity were recorded, followed by Kainic Acid induced seizures for the remainder of the experiment. The seizure latency, type, duration, and frequency as well as severity were recorded to assess differences in seizure susceptibility as a function of Sex and Lead Exposure. These results suggest that developmental lead poisoning may cause persistent deficits in GABAergic inhibitory processes that may underlying issues with sensory integration, coordinated activity/associativity, and the ability to regulate cognitive and behavioral neural networks due to elevated brain excitability. Further, the present work suggests that developmental lead poisoning, in theory. could be alleviated by psychotropic medications directed at increasing GABAergic tone to regain excitation:inhibition balancing to improve cognitive and behavioral function across the lifespan once detected.