Lead Encephalopathy in the Developing Rat: Effect Upon Myelination

The effects of chronic lead intoxication were studied by examining the optic nerve of mice given lead-containing mother's milk from day 1 to day 21 of life. Biochemical assays for myelin basic protein, 2',3'-cyclic nucleotide phosphodieterase, and cerebroside sulfotransferase showed that the total amount of myelin produced by the lead-exposed animals was decreased. Lead exposure did not alter the number of oligodendroglia or the relationship between axons and myelin sheaths. The hypomyelination was paralleled by a reduction in size of optic axons in the lead-exposed animals. The data suggest that chronic exposure to lead in developing mice results in a primary effect on neurons and that hypomyelination is secondary to reduction in axon size.

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“…They were then group-housed by sex. These animals and the controls were studied at 5,8,11,13,15,19,23, and 28 days. …”

Section: Methodsmentioning

confidence: 99%

Chronic lead intoxication: Effects on developing optic nerve

Tennekoon

Aitchison

Frangia

et al. 1979

Annals of Neurology

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“…A more detailed description of the animal model, morphometric procedures, and chemical analyses appears in our earlier reports (9,10).…”

Section: Methodsmentioning

confidence: 99%

Effect of Lead Intoxication on the Postnatal Growth of the Rat Nervous System

Krigman¹,

Hogan²

1974

Environmental Health Perspectives

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Lead encephalopathy was induced in developing Long-Evans rats by adding lead carbonate (4% w/w) to the diet of nursing mother immediately after delivery. The morphological and biochemical features of cerebral ontogenesis were studied in 30-dayold rats.By the 30th postnatal day, the overall effect of lead intoxication was retardation of brain growth. The mass of both the cerebral gray and white matter was appreciably reduced in the lead rats without any reduction in cell populations. While the neuronal population was preserved, the growth of neurons was reduced and their maturation retarded. The retarded neuronal growth was characterized by the limited proliferation of processes in the neuropil and by the reduction in the number of synapses per neuron. However, synaptogenesis was neither delayed nor perturbed but reduced by the limited development of neuronal dendritic fields. The myelination was altered and its cerebral content significantly reduced. The effect of lead on myelination was one of hypomyelination. The hypomyelination appears to be primarily related to retarded growth and maturation of the neuron and is not a reflection of a defect in the myelinating glia or a delay in the initiation of myelination. IntroductionThe vulnerability of the nervous system to the toxic effects of lead is most evident in the young. While the neural aspects of plumbism have been the subject of numerous studies, we still have much to learn about the extent of the effects of lead on the nervous system. This is particularly true for body lead burdens in children which have been previously considered nontoxic (1, 2). The nervous system of the young is obviously different from that of the adult. The episodic nature of the growth and maturation of the developing nervous system may make the young more vulnerable at selected periods (3) to a hostile environment than the adult.In an attempt to define the effects of lead on the developing nervous system, we have studied the model of lead encephalopathy May 1974 187 described by Pentschew and Garro (4). The model uses the nursing rat and is characterized by selected morphological features resembling those of clinical encephalopathy. This report is based upon quantitative morphometric and biochemical analyses of postnatal brain development and contains our findings on the effects of lead on neuronal growth and maturation, synaptogenesis, and myelination. The studies reported herein were limited to the 30th postnatal day. By this time the nervous system is highly developed: the brain weight is nearly threefourths that of an adult (5), neurogenesis has stopped (5, 6), synaptogenesis has nearly ceased (7,8), and the most active period of myelination is over (3); also, the pups are already weaned. Materials and MethodsA more detailed description of the animal model, morphometric procedures, and chemical analyses appears in our earlier reports (9, 10). Animal ModelLead intoxication was produced in the Long-Evans strain of rats by the procedure described by Pentschew and Garro (4). Immediate...

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“…The first systematic study of lead toxicity by Pentschew and Garro [14] found hemorrhage on the cerebellar cortex and the animals developed hindlimb ataxia. Refinements of this study showed paraplegia and hemorrhage to be dose and time dependent [56,57].…”

Section: Discussionmentioning

confidence: 83%

Dendritic Alterations of Cerebellar Purkinje Neurons in Postnatally Lead-Exposed Kittens

Patrick

Anderson²

2000

Dev Neurosci

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Many investigations have sought to determine the effect of lead exposure on the development of the cerebellum. This study addresses the effects of postnatal lead exposure in kittens on dendritic development of Purkinje cells. Golgi-Cox filled cells were used to measure dendritic branching patterns, spine density, height, width and distance from the cerebellar surface. The results revealed a significant increase in spine density and altered patterns of dendritic branching. Complex dendritic branching was evident with a progressive shift in peak branching peripherally. Lead-exposed Purkinje cells showed early sprouting with subsequent pruning. At 5 weeks of age dendritic branches on experimental cells were increased along the entire dendritic extent. Control Purkinje cells showed initial sprouting with subsequent pruning. Normal developmental growth spurts and lead-induced effects were evident on dendritic height, width and distance from the surface. Cerebella stained with hematoxylin and eosin and cresyl violet acetate showed no evidence of vascular damage or other pathologies. These findings corroborate the evidence of hyperspiny dendritic formation representing an important mechanism of neuronal plasticity. In regard to morphological effects of lead on rodents, the hyperspiny Purkinje cell dendrites and patterns of dendritic growth in lead-treated kittens offer an alternative interpretation of neurobehavioral findings of lead-burdened children. The results are discussed with reference to other aspects of lead exposure and neural development.

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Lead Encephalopathy in the Developing Rat: Effect Upon Myelination

Cited by 74 publications

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Chronic lead intoxication: Effects on developing optic nerve

Chronic lead intoxication: Effects on developing optic nerve

Effect of Lead Intoxication on the Postnatal Growth of the Rat Nervous System

Dendritic Alterations of Cerebellar Purkinje Neurons in Postnatally Lead-Exposed Kittens

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