Moderate lead exposure elicits neurotrophic effects in cerebral cortical precursor cells in culture

Abstract

Lead (Pb) persists as an environmental toxicant despite aggressive environmental and occupational regulation. Neurotoxicological effects of acute Pb poisoning range from subtle cognitive deficits, to clumsiness and ataxia, to coma and seizures. In adult neurotoxicity, reductions of blood Pb levels are often associated with reversal of clinical signs. In children, however, the effects are more likely to endure, with even low levels of chronic Pb exposure correlating with decreasing IQ. These persistent effects likely result from neurodevelopmental insults, such as altered cell survival or maturation, although the mechanisms have not been fully defined. In the present study we define the effects of moderate-level Pb exposure on mammalian neurogenesis using a well-characterized cortical precursor model. Gestational day 14.5 rat cerebral cortical precursor cells were cultured in defined media and cell number, precursor proliferation, apoptosis, and neuritic process outgrowth were assessed following exposure to a range of Pb acetate concentrations. Surprisingly, whereas a concentration of 30 microg/ml Pb acetate was acutely toxic to neurons, concentrations between 1 and 10 microg/ml Pb acetate (approximately 3 microM and 30 microM Pb, respectively) increased cell number: 10 times as many cells exposed to 10 microg/ml Pb were present on day 4 as compared to control. The increase in cell number was not a result of increased proliferation, however, as DNA synthesis did not increase. Rather, Pb exposure maintained the survival of cortical precursors, as the progressive apoptosis occurring under control conditions was markedly reduced by the metal. Additionally, neuritic process initiation and outgrowth increased in a concentration-dependent manner, with processes four times as abundant on day 1 and twice as long on day 2. These results suggest that brief exposure to lead during neurogenesis directly affects cell survival and process development, potentially altering cortical arrangement. Consequently, alterations in neural circuitry may underlie some of the neurological effects of Pb exposure during brain development.

Pre- and Neonatal Exposure to Lead (Pb) Induces Neuroinflammation in the Forebrain Cortex, Hippocampus and Cerebellum of Rat Pups

“…We also proved that pre-and neonatal exposure to Pb results in numerous disorders, as confirmed by behavioral and cognitive tests [36,37]. It is also known so far that Pb impairs the functioning of progenitor cells, leading to structural changes in the hippocampus [16,38,39] and cerebral cortex [40,41]. Pb also disrupts developmental cortical plasticity, causing dysfunction in neurodevelopment [25].…”

A case of multiple sclerosis improvement following removal of heavy metal intoxication

“…Indeed, the neurotoxic response to methyl-mercury has been shown to be dependent on the cell type, neural stem cells being more susceptible; moreover, methyl-mercury has been shown able to trigger multiple cell death pathways that may be concomitantly activated (Ceccatelli et al 2010). Brief exposure to lead during neurogenesis was demonstrated efficient in directly affecting cell survival and process development, potentially altering cortical arrangement (Davidovics and DiCicco-Bloom 2005). Aluminium-induced neural cell death (displayed as apoptosis) has been recently related to inactivation of the Bax gene, which is involved in the maintenance and survival of neurons and neuron-supporting cells, as glial cells (Zhang et al 2010).…”

The detrimental effects of lead on human and animal health

“…In addition, a testicular damage in male rats which had levels of 30 µg/dL of lead in blood was detected. Davidovics and DiCicco-Bloom [ 37 ] stated an in vitro changes valuation to mammalian neurogenesis via a model of well-characterized cortical precursor following exposure to lead. In rat’s kidney, an influence of lead on lipid peroxidation, renal function, and expression of heme oxidation was evaluated by Vargas et al .…”