Myelin Deficits Produced by Early Postnatal Exposure to Inorganic Lead or Triethyltin Are Persistent

Abstract

Long‐Evans rat pups were exposed to either inorganic lead (400 mg Pb as lead acetate/kg body weight/day) or triethyltin sulfate (1.0 mg/kg body weight/day), by gastric intubation, from 2 days through 29 days of age. The rats were then weaned and placed on standard lab chow ad libitum. At 30 days of age, leadtreated rats exhibited statistically significant decreases in body and brain weights (22% and 17%, respectively), and the concentration of forebrain myelin was significantly reduced, by 21% relative to the 4.9 mg myelin protein/g brain in control rats. Although these animals recovered from the body weight deficits after several months, the deficits in brain weight and myelin concentration were still present at 120 days of age. This suggests that the lead‐induced myelin deficits were permanent. Lead levels in brain, which were maximal at 30 days of age when the treatment was terminated, decreased more slowly than in other organs and were still 30% of maximal levels at 120 days of age. Triethyltin‐treated animals also had significantly decreased body and brain weights (20% and 11%, respectively) at 30 days of age, and an even more severe reduction in forebrain myelin concentration (33%). These animals also regained a normal body weight by 120 days of age, but again the deficits in brain weight and myelin concentration persisted. Tin levels in brain and other organs had decreased to control levels by 60 days of age. Animals malnourished by maternal deprivation to match the body weights of the treated animals had myelin deficits that were less severe than those in the treated animals at 30 days of age (approximately 11% less than controls); however, these myelin deficits also persisted throughout the subsequent 90‐day recovery period examined. The apparent lack of recovery from CNS myelin deficits produced by neonatal exposure to different heavy metals or to malnutrition reemphasizes the vulnerability of the developing nervous system to a wide range of metabolic insults.

Proton Magnetic Resonance Spectroscopy in Adults with Childhood Lead Exposure

“…Lead can change white-matter organization and functioning via altered expression of genes essential to myelin formation (Deng and Poretz 2001; Zawia and Harry 1995), delayed differentiation of oligodendrocyte progenitors (Deng and Poretz 2001; Zawia and Harry 1995), delayed myelin accumulation (Toews et al 1980, 1983), disordered oligodendrocyte architecture (Dabrowska-Bouta et al 1999), structural changes within the myelin sheath and disintegration of the multilamellar structure (Dabrowska-Bouta et al 2008), and astrogliosis (Selvin-Testa et al 1994; Struzynska et al 2001, 2007). …”

Altered myelination and axonal integrity in adults with childhood lead exposure: A diffusion tensor imaging study

“…Lead may act as a calcium analog in neurons with exposure inhibiting glutamate release through binding to the NMDA receptor in an age-dependent and region specific manner (Guilarte TR, 1994), which would result in structural and functional differences despite uniform concentrations within the brain. Lead alters white matter via expression of genes essential to myelin formation (Deng W and Poretz RD, 2001, Zawia NH and Harry GJ, 1995), delayed myelin accumulation (Toews AD, 1983, Toews AD, 1980), delayed differentiation of oligodendrocyte progenitors (Deng W and Poretz RD, 2002,), disordered oligodrocyte architecture (Dabrowska-Bouta B, 1999), structural changes within the myelin sheath and disintegration of the multi-lamellar structure (Dabrowska-Bouta B, 2008) and astrogliosis (Selvin-Testa A, 1994, Struzynska L, 2001, Struzynska L, 2007). In exposing the immature rat brain to prolonged lead exposure, Struzynska demonstrated glial cell activation occurs with the elevation of GFAP and S-100βproteins, accompanied by increased cytokine production and evidence of axonal damage (Struzynska L, 2007).…”

Regional alterations of brain biogenic amines and GABA/glutamate levels in rats following chronic lead exposure during neonatal development

“…Preliminary studies by Pentschew and Garro (1966) on lead-exposed rats revealed the severe involvement of the neuraxis. Lead can induce inhibition of monoamine oxidase (Unni and Caspers 1985), phenylethanolamine-N-methyltransferase (Caspers 1982), brain adenyl cyclase (Nathanson and Bloom 1975): CNS myelination (Toews et al 1980(Toews et al , 1983, and acetylcholine release (Silbergeld et al 1974). Encephalopathy with seizures and coma is one of the most striking and serious complications of lead poisoning.…”