Lead Poisoning Effects on Brain Excitability: Using Fourier Transforms to Parse Seizures Through Brain Waves and Slow and Fast Ripples

Abstract

Neurodevelopmental exposure to lead poisoning causes alterations in the GABA-shift from early excitation-to-inhibition balancing. The GABA-shift is a hallmark event that when disrupted is a well-known neurodevelopmental cause of seizure disorders and increased brain excitability that is subthreshold to seizure onset. Lead poisoning in high-exposures can cause both seizure and brain encephalopathy, but at low-exposures are not well studied. The present study investigated the effects of both low- and high-exposures (i.e., 150 ppm and 1,000 ppm lead acetate) to lead poisoning during perinatal development on later-life adult (postnatal day 55-70) rats pharmacologically induced with pilocarpine seizures as a form of status epilepticus. The raw seizure data that were recorded over 1-hr post pilocarpine (380 mg/kg i.p.) were mathematically deconstructed using a fourier transformation to isolate the alpha, beta, delta, gamma, and theta brain waves as well as slow and fast ripples. The topography of the brain waves and ripples show that lead treated rats causes sex-dependent effects on seizure generation as evidenced as increased brain excitability when compared to control rats. Further, lead male rats have elevated slow and fast ripples when compared to lead female rats. Interestingly, gamma, beta, alpha, theta, and delta brain waves were disrupted in both a sex- and lead dose-dependent manner. The most disruption was caused to the gamma (cognition and learning) and beta (attentional focus) with more subtle differences observed in alpha and delta (resting) and theta (limbic system) wave functions. Taken together, this topographical analysis of the seizures induced by developmental lead exposure revealed that dependent upon sex and lead exposure that different patterns of brain excitability occur as pathophysiological outcomes later in life. These data suggest that lead may cause subthreshold levels of brain excitability that may be vulnerable to other insults, drugs, or injuries making the lead exposed brain more susceptible for seizures later in life.