Impairment of long-term potentiation and learning following chronic lead exposure

Altmann, L; Weinsberg, Frank; Sveinsson, Karolina; Lilienthal, Hellmuth; Wiegand, Herbert; Winneke, Gerhard

doi:10.1016/0378-4274(93)90085-c

Cited by 130 publications

(35 citation statements)

References 13 publications

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“…LTP is reduced in animal strains that learn less well (23), including mutant animals (24), and LTP is also reduced in aged animals (25,26). Previous studies in our and other laboratories have shown that LTP is reduced upon exposure to lead (27,28) and PCBs (29), consistent with our central hypothesis that LTP is a, or perhaps the, central target of environmental agents that alter cognitive function. However, LTP is not pharmacologically the same process in all brain areas.…”

supporting

confidence: 86%

“…We (27,(29)(30)(31) and others (28,44,45) have shown that LTP is reduced by both lead and PCBs in certain brain areas, including the piriform cortex, hippocampal CA1 and dentate gyrus, and visual cortex. Hippocampal CA3 has been less studied, although Gutowski et al (46) report that they did not observe any effect of developmental exposure to lead on LTP at this synapse.…”

Section: Lead and Pcbs Have Similar Effects On Ltpmentioning

confidence: 72%

“…Exposed females were not different from controls on measures of number of lever presses within the FI (the measure of impulsiveness) or IRTs (bursting), a measure of hyperactivity. Schantz et al (56) perinatally exposed male and female rats to one of three orthosubstituted PCBs (28,118, or 153) and tested the animals on a delayed spatial-alternation task. At the higher doses of all PCB congeners and for all periods of delay, significantly slower acquisition (relative to controls) was found in female but not in male rats.…”

Section: Neurobehavioral Effects Of Lead and Pcbs And Their Relationsmentioning

confidence: 99%

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Electrophysiologic and behavioral effects of perinatal and acute exposure of rats to lead and polychlorinated biphenyls.

Carpenter

Hussain

Berger

et al. 2002

Environ Health Perspect

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Lead and polychlorinated biphenyls (PCBs) both cause a reduction of intelligence quotient and behavioral abnormalities in exposed children that have features in common with attention deficit hyperactivity disorder. We have used rats as a model to study the effects of both perinatal and acute exposure to lead or PCBs in an effort to compare and understand the mechanisms of these nervous system decrements. Long-term potentiation (LTP) is an electrophysiologic measurement that correlates well with cognitive ability. We have determined the effects of chronic perinatal exposure to lead or PCB 153 as well as acute application of these substances to isolated brain slices, with recordings in two areas of the hippocampus, CA1 and CA3. Both substances, whether chronically or acutely applied, significantly reduced LTP in CA1 in animals at age 30 and 60 days. In CA3, they reduced LTP in 30-day animals but potentiated it in 60-day animals. Although neither lead nor PCB 153 alters baseline synaptic transmission at low stimulus strengths, at higher levels they induce changes in the same direction as those of LTP. These results show surprisingly similar actions of these quite different chemicals, and the similarity of effects on chronic and acute application indicates that effects are both pharmacologic and developmental. Behavioral studies of rats exposed to PCBs from contaminated fish show hyperactivity, impulsiveness, and increased frustration relative to unexposed controls. These results demonstrate that lead and PCBs have similar effects on synaptic plasticity and behavior and suggest that the compounds may act through a common mechanism. Key words: brain slice, extinction, frustration, hippocampus, hyperactivity, input-output curves, long-term potentiation, perinatal exposure.

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supporting

confidence: 86%

Section: Lead and Pcbs Have Similar Effects On Ltpmentioning

confidence: 72%

Section: Neurobehavioral Effects Of Lead and Pcbs And Their Relationsmentioning

confidence: 99%

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Electrophysiologic and behavioral effects of perinatal and acute exposure of rats to lead and polychlorinated biphenyls.

Carpenter

Hussain

Berger

et al. 2002

Environ Health Perspect

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“…Reduced head dips and decreased shuttle-avoidance response suggest hyperactivity, decreased exploratory behavior, and impairment in learning and memory. These impairments in the present study may be attributed to the increased hyperactivity in the rats (Altmann et al, 1993). These alterations in behavior may also be due to the direct inhibitory effect of lead on neurotransmitters in the adult brain (Ma et al, 1999).…”

Section: Head Dipsupporting

confidence: 46%

Reversal of Lead-Induced Neuronal Apoptosis by Chelation Treatment in Rats: Role of Reactive Oxygen Species and Intracellular Ca²⁺

Flora¹,

Saxena²,

Mehta³

2007

J Pharmacol Exp Ther

150

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Lead, a ubiquitous and potent neurotoxicant causes several neurophysiological and behavioral alterations. Toxic properties of lead have been attributed to its capability to mimic calcium and alter calcium homeostasis. In this study, we have addressed the following issues: 1) whether chelation therapy could circumvent the altered Ca 2ϩ homeostasis and prevent neuronal death in chronic lead-intoxicated rats, 2) whether chelation therapy could revert altered biochemical and behavioral changes, 3) whether combinational therapy using two different chelating agents was more advantageous over monotherapy in lead-treated rats, and 4) what could be the mechanism of neuronal apoptosis. Results indicated that lead caused a significant increase in reactive oxygen species, neuronal nitric-oxide synthetase, and intracellular free calcium levels along with altered behavioral abnormalities in locomotor activity, exploratory behavior, learning, and memory that were supported by changes in neurotransmitter levels. A fall in membrane potential, release of cytochrome c, and altered bcl 2 /bax ratio indicated mitochondrial-dependent apoptosis. Most of these alterations reverted toward normal level following combination therapy over monotherapy with calcium disodium EDTA (CaNa 2 EDTA) or monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA). It could be concluded from our present results that combined therapy with CaNa 2 EDTA and MiADMSA might be a better treatment protocol than monotherapy with these chelators in lead-induced neurological disorders. We for the first time report the role of Ca 2ϩ in regulating neurological dystrophy caused by chronic lead exposure in rats and its recovery with a two-course treatment regime of mono or combination therapy.

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“…When LTP in animals is saturated, further learning is impaired (13). LTP is blocked by lead (14,15), an environmental contaminant that also causes a reduction in IQ. We previously showed (16) that acute exposure of hippocampal brain slices of normal rats to PCB mixtures results in a reduction of LTP with exposures that did not significantly alter other aspects of synaptic transmission.…”

mentioning

confidence: 99%

In Vivo and in Vitro Exposure to PCB 153 Reduces Long-Term Potentiation

Hussain¹,

Győri²,

DeCaprio³

et al. 2000

Environmental Health Perspectives

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Impairment of long-term potentiation and learning following chronic lead exposure

Cited by 130 publications

References 13 publications

Electrophysiologic and behavioral effects of perinatal and acute exposure of rats to lead and polychlorinated biphenyls.

Electrophysiologic and behavioral effects of perinatal and acute exposure of rats to lead and polychlorinated biphenyls.

Reversal of Lead-Induced Neuronal Apoptosis by Chelation Treatment in Rats: Role of Reactive Oxygen Species and Intracellular Ca²⁺

In Vivo and in Vitro Exposure to PCB 153 Reduces Long-Term Potentiation

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Impairment of long-term potentiation and learning following chronic lead exposure

Cited by 130 publications

References 13 publications

Electrophysiologic and behavioral effects of perinatal and acute exposure of rats to lead and polychlorinated biphenyls.

Electrophysiologic and behavioral effects of perinatal and acute exposure of rats to lead and polychlorinated biphenyls.

Reversal of Lead-Induced Neuronal Apoptosis by Chelation Treatment in Rats: Role of Reactive Oxygen Species and Intracellular Ca2+

In Vivo and in Vitro Exposure to PCB 153 Reduces Long-Term Potentiation

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Reversal of Lead-Induced Neuronal Apoptosis by Chelation Treatment in Rats: Role of Reactive Oxygen Species and Intracellular Ca²⁺