Morphometric effects of postnatal lead exposure on hippocampal development of the 15-day-old rat

Campbell, J.B.; Woolley, Dorothy E.; Vijayan, Vijaya K.; Overmann, Stephen R.

doi:10.1016/0165-3806(82)90056-6

Cited by 63 publications

(16 citation statements)

References 56 publications

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“…In addition, control animals had Pb nearly three to four times higher in the choroid plexus than in other brain regions examined. Moreover, these results confirm the observation in humans and rats that upon exposure Pb mainly accumulated in the hippocampus, an area that coordinates learning and memory (Campbell et al, 1982;Scheuhammer & Cherian, 1982).…”

Section: Discussionsupporting

confidence: 77%

Transport of L-[ 125 I]Thyroxine bY iN Situ Perfused Ovine Choroid Plexus: Inhibition by Lead Exposure

Zheng

Deane

Redžić

et al. 2003

Journal of Toxicology and Environmental Health, Part A

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Lead (Pb) exposure hinders brain development in children by mechanisms that remain unknown. Previous evidence shows that sequestration of Pb in the choroid plexus lowers the production and secretion of transthyretin (TTR), a thyroxine (T 4 ) transport protein, from the choroid plexus into the cerebrospinal fluid (CSF). This study was undertaken to characterize the uptake kinetics of T 4 by the choroid plexus and to determine if in vivo Pb exposure altered the T 4 uptake in an in situ perfused ovine choroid plexus model. Sheep received ip injections of Pb acetate (20 mg Pb/kg) or Na acetate (as the controls) every 48 h for a period of 16 d. The [ 125 I]T 4 uptake was determined by a paired-tracer perfusion method using 0.5μCi [ 125 I]T 4 and 2 μ Ci [ 14 C]mannitol at various concentrations of unlabeled T 4 (trace to 20 μM). The flux of [ 125 I]T 4 into the choroid plexus followed Michaelis-Menten kinetics with the maximum flux (V max ) of 56.6 nmol/min/g and halfsaturation constant (K m ) of 10.7 μmol/L, suggesting an evident saturable influx of T 4 into the choroid epithelium. In vivo Pb exposure in these sheep resulted in a significant accumulation of Pb in the choroid plexus and hippocampus. Pb treatment diminished the V max by 63.7% of control, but did not alter K m . The maximal cellular uptake (U max ) and net uptake (U net ) in Pb-treated animals were 2.1-fold and 1.9-fold, respectively, lower than those of control. Exposure to Pb, however, did not significantly change the flow rate through the choroid plexus. Data suggest that the choroid plexus may serve as a significant site for T 4 transport into the CSF, and Pb exposure may hinder the influx of T 4 from the blood into the choroid plexus. The brain requires, but does not synthesize, thyroid hormones for its normal development, maturation, metabolism, and function (Dussault & Ruel, 1987;Legrand, 1984). Although thyroxine (T 4 ), a major type of thyroid hormone in blood and cerebrospinal fluid (CSF) circulation, is fairly lipophilic, the data from human and animal studies indicate that the transport of thyroxine between blood and the cerebrospinal fluid is restricted and does not follow simple diffusion mechanism responsive to mass balance (Ingenbleek & Young, 1994 Kirkegaard & Faber, 1991;Schreiber et al., 1990;Zheng et al., 2001). Thus, it has been suggested that the blood-brain barrier and/or blood-CSF barrier controls thyroxine availability to the cerebral compartment (Kirkegaard & Faber, 1991;van Raaij et al., 1994).Thyroxine enters the CSF and brain parenchyma by two possible routes. The hormone may cross the blood-brain barrier located at the cerebral capillary endothelium into the brain extracellular fluid (ECF) and then by diffusion enter the CSF. This proposed mechanism is supported by the observation of a wide distribution of radiolabeled [ 125 I]T 4 throughout the brain after intravenous injection, but not with intracerebroventricular (icv) injection of free [ 125 I]T 4 (Blay et al., 1993), although the possibility of interference fro...

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Section: Discussionsupporting

confidence: 77%

Transport of L-[ 125 I]Thyroxine bY iN Situ Perfused Ovine Choroid Plexus: Inhibition by Lead Exposure

Zheng

Deane

Redžić

et al. 2003

Journal of Toxicology and Environmental Health, Part A

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“…Lead accumulates in and targets both choroid plexus and hippocampus (51,(66)(67)(68) and this phenomenon may relate to the intimate anatomic contact of both tissues. Perhaps closer anatomical location renders the hippocampus more susceptible to lead diffused from the choroid plexus.…”

Section: Concept Of Blood-brain Regional Barriersmentioning

confidence: 99%

Neurotoxicology of the Brain Barrier System: New Implications

Zheng

2001

Journal of Toxicology: Clinical Toxicology

103

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The concept of a barrier system in the brain has existed for nearly a century. The barrier that separates the blood from the cerebral interstitial fluid is defined as the blood-brain barrier, while the one that discontinues the circulation between the blood and cerebrospinal fluid is named the blood-cerebrospinal fluid barrier. Evidence in the past decades suggests that brain barriers are subject to toxic insults from neurotoxic chemicals circulating in blood. The aging process and some disease states render barriers more vulnerable to insults arising inside and outside the barriers. The implication of brain barriers in certain neurodegenerative diseases is compelling, although the contribution of chemical-induced barrier dysfunction in the etiology of any of these disorders remains poorly understood. This review examines what is currently understood about brain barrier systems in central nervous system disorders by focusing on chemical-induced neurotoxicities including those associated with nitrobenzenes, N-methyl-D-aspartate, cyclosporin A, pyridostigmine bromide, aluminum, lead, manganese, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and 3-nitropropionic acid. Contemporary research questions arising from this growing understanding show enormous promises for brain researchers, toxicologists, and clinicians.

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“…For example, the teratogenic and toxic effects resulting from exposure to lead compounds have been well documented (e.g., Campbell, Wooley, Vijayan, & Overmann, 1982;Overmann, 1977). Lead exposure in both humans and laboratory animals produces impairments in learning and memory consistent with the hypothesis that these effects are the result of lead-induced disruption of hippocampal function (Alfano & Petit, 1981).…”

Section: Early Lifementioning

confidence: 87%

Neuronal Plasticity in the Mammalian Brain: Relevance to Behavioral Learning and Memory

Teyler

Fountain²

1987

Child Development

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Much recent activity in the neurosciences relates to the search for the brain mechanisms underlying learning and memory. In recent years a brain circuit in cerebellum and brainstem has been discovered that is responsible for the learning of a simple motor response (nictitating membrane movement). This has provided a model for neuroscientists to use in understanding the brain circuits involved in this simple form of learning and, by extension, to more complex forms ultimately, and a means of exploring the changes in neural function underlying the learning. An enduring change in neural function is represented by long-term potentiation (LTP), an alteration in synaptic efficacy seen in hippocampus and other areas. LTP can be induced experimentally and occurs as a concomitant of learning. We review data suggesting that different brain circuits may underlie different forms of learning and memory. Several current theories of learning and memory with respect to hippocampal and other brain circuit involvement are considered. We conclude with the behavioral and physiological effects of exposure to teratogens or toxins and the CNS alterations associated with dementia.

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Morphometric effects of postnatal lead exposure on hippocampal development of the 15-day-old rat

Cited by 63 publications

References 56 publications

Transport of L-[ 125 I]Thyroxine bY iN Situ Perfused Ovine Choroid Plexus: Inhibition by Lead Exposure

Transport of L-[ 125 I]Thyroxine bY iN Situ Perfused Ovine Choroid Plexus: Inhibition by Lead Exposure

Neurotoxicology of the Brain Barrier System: New Implications

Neuronal Plasticity in the Mammalian Brain: Relevance to Behavioral Learning and Memory

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