The developing cholinergic system as target for environmental toxicants, nicotine and polychlorinated biphenyls (PCBs): Implications for neurotoxicological processes in mice

Abstract

During neonatal life, offspring can be affected by toxic agents either by transfer via mother's milk or by direct exposure. In many mammalian species the perinatal period is characterized by a rapid development of the brain - "the brain growth spurt" (BGS). This period in the development of the mammalian brain is associated with numerous biochemical changes that transform the feto-neonatal brain into that of the mature adult. In rodents, the cholinergic transmitter system undergoes a rapid development during the neonatal period, a time when spontaneous motor behaviour also reaches peak activity. We have observed that low-dose exposure to environmental toxicants such as nicotine, polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDE, flame retardants) during the "BGS" can lead to irreversible changes in adult brain function in the mouse. The induction of persistent effects on behaviour and cholinergic nicotinic receptors in the adult animal appears to be limited to a short period during neonatal development. Furthermore, the neurotoxic effects were shown to develop over time, indicating a time-response/time-dependent effect. This indicates that environmental toxicants, such as nicotine, PCBs and probably PBDEs, might be involved in the slow, implacable induction of neurodegenerative disorders and/or interfere with normal aging processes.

Cholinergic Circuits and Signaling in the Pathophysiology of Schizophrenia

“…Experimental studies have shown that during development, the cholinergic system is especially sensitive to environmental insults (e.g., ethanol, lead, organophosphates, tobacco smoke; Eriksson et al, 2001;Reddy et al, 2003;Robinson, 2002;Thomas et al, 2000). These and other insults would certainly have the potential to interact with genetic vulnerabilities affecting brain development to produce deficits which could contribute to disease states.…”

Acute exposure to DE‐71: Effects on locomotor behavior and developmental neurotoxicity in zebrafish larvae

“…It has also been shown that during this period of rapid development, the brain is vulnerable to insults from xenobiotics [7]. Exposure to PBDEs has been associated with developmental neurotoxicity since the beginning of the 21st century [1,8], and the nature of potential adverse effects associated with this exposure continue to be a concern [9].…”

“…Many studies of the neurotoxicity arising from exposure to PBDEs have been performed with rodents, and these have documented findings such as alterations in spontaneous motor activity or in learning and memory or disruption of habituation [3,8,10]. Several studies have shown structural and functional alterations in the brains of PBDE-exposed animals.…”

Effects of Maternal Stress during Different Periods of Pregnancy on the Early Neurobehavioral Response of Rats

“…Following the maturation of certain neural reflexes and motor coordination may give us an insight into the neurodevelopment of prenatally stressed animals. It has been shown that reflex ontogeny in rodents is influenced by several factors such as undernutrition, maternal care, toxic agents, environmental enrichment, genetic background [22][23][24][25][26][27][28][29][30]. We have previously described that perinatal hypoxic and toxic injuries remarkably delay the neurobehavioral development but 3-hr-long maternal separation induces only slight changes [31][32][33][34].…”