Lilo Altmann

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

Chronic lead exposure during brain development is known to affect functions of the central nervous system. We exposed rats chronically to low levels of lead at different developmental stages in order to determine the most sensitive periods of exposure. Active avoidance learning and hippocampal long-term potentiation were tested in the same animals. If the exposure period comprised the prenatal and the early postnatal phase and was continued into adulthood, learning as well as long-term potentiation were impaired. Starting the exposure not before 16 days postnatally, however, neither affected learning nor hippocampal potentiation. These results reflect the higher vulnerability of the immature as compared to the mature hippocampus to lead-induced functional deficits.

Cognitive and Sensorimotor Functions in 6-Year-Old Children in Relation to Lead and Mercury Levels: Adjustment for Intelligence and Contrast Sensitivity in Computerized Testing

Within a larger environmental health screening program neurobehavioral measures were taken in 384 6-year-old children (mean age 74 months) in the cities of Leipzig, Gardelegen, and Duisburg. Lead concentrations in venous blood samples (PbB) and urinary mercury excretion in 24-h samples (HgU) were measured as markers of environmental exposure by electrothermal AAS. Dependent variables included two subtests from the WISC [vocabulary (V) and block design (BD)] as well as five tests from the NES2 [pattern comparison, pattern memory, tapping, simple reaction time, and the continuous performance test (CPT; child version)]. In addition, visual functions [visual acuity (TITMUS-test) and contrast sensitivity (FACT)] were tested as covariates. The overall average PbB (geometric mean) was 42.5 microg/l (upper 95% value = 89 microg/l). The overall average mercury excretion (HgU) was 0.16 microg/24 h. Whereas no significant or borderline associations between HgU and any of the target variables was found, significant negative associations were observed between PbB and verbal intelligence (WISC vocabulary but not WISC Block Design) and false-positive responses (false alarms), as well as false-negative responses (miss) in the CPT. Whereas parental education was the most important confounder for WISC performance, visual contrast sensitivity and computer familiarity also proved predictive for performance in several computer-based NES subtests. It is concluded that non-IQ measures, namely measures of sustained attention, are negatively affected in children with 95% of blood-lead levels below 90 microg/l, even after adjustment for intelligence and contrast sensitivity, whereas the causative role of lead in altering IQ functions remains somewhat equivocal, because important covariates could not be controlled for.

LONG-TERM POTENTIATION IN RAT HIPPOCAMPAL SLICES IS IMPAIRED FOLLOWING ACUTE LEAD PERFUSION

Orthodromically evoked field potentials were recorded in the CA1 region of hippocampal slices while perfusing the slices with media containing lead acetate. High-frequency stimulation (HFS) was applied to the stratum radiatum during lead perfusion. In half of the slices investigated, HFS resulted in an initial increase of the evoked responses which decayed again after about 10 min. In the other half the evoked responses increased only after the washout of lead and this potentiation was comparable to untreated controls. The lead-induced depression of the long-term potentiation might be related to the behavioral deficits observed in chronically lead-exposed mammals.

Neurophysiological and psychophysical measurements reveal effects of acute low-level organic solvent exposure in humans

SummaryThe organic solvent tetrachloroethylene (Per) is proposed to be a human neurotoxicant. In order to evaluate whether the sensory system is affected by Per at low concentrations, two groups of male volunteers were exposed in an inhalation chamber to 10 and 50 ppm Per, respectively. During the inhalation exposure, which lasted for 4 h per day on four consecutive days, visually evoked potentials (VEPs) and brainstem auditory evoked potentials (BAEPs) were measured. In addition, in some of these volunteers, the visual contrast sensitivity was determined psychophysically. In the group exposed to 50 ppm Per, the VEP peak latencies N75, P100 and N150 increased in the course of the inhalation period. A comparison of the two groups revealed statistically significant differences of these latency changes during Per exposure. In contrast, the BAEPs of the two groups did not differ significantly during the whole exposure period. The contrast sensitivity functions showed a tendency of increased threshold contrasts at low and intermediate spatial frequencies during exposure to 50 ppm Per. The results indicate visual system dysfunctions in terms of delayed neuronal processing time and altered contrast perception due to acute Per exposure.

Visual Functions in 6-Year-Old Children in Relation to Lead and Mercury Levels

Within a larger comparative environmental health screening program in East and West Germany we investigated functions of the developing visual system in field experiments in a total of 384 children living in three different areas. Visual functions were assessed neurophysiologically by visual-evoked potentials (VEPs) and psychophysically by measuring the contrast sensitivity (CS). Blood lead concentrations and urinary mercury levels were used as markers of environmental and/or amalgam-derived exposure, respectively. The relationships among lead and mercury concentrations and the neurophysiological and psychophysical outcomes were investigated by means of linear regression analysis. After adjusting for confounding effects, statistically significant lead-related changes were found only for some of the VEP interpeak latencies, while some of the CS values were significantly reduced with increasing mercury concentrations. All other outcome variables were not significantly related to lead or mercury levels. It is concluded that even at blood lead levels in the range of 14 to 174 micrograms/l and at very low urinary mercury levels subtle changes in visual system functions can be measured.

Chronic prenatal and postnatal Pb2+ exposure increases [3H]MK801 binding sites in adult rat forebrain

We have measured the binding of [3H]MK801 to the N-methyl-D-aspartate (NMDA) receptor-ion channel in membrane preparations from adult rat forebrain exposed to lead (Pb2+) during gestation, lactation, and postweaning. Our results indicate a 30.9% increase in the number of [3H]MK801 binding sites in Pb2+ exposed animals relative to controls. No significant changes in the affinity constant were observed. The level of blood Pb2+ for which such changes were measured was 13.9 +/- 2.8 micrograms/dl. These results indicate that alterations in the NMDA receptor-ion channel complex are present at blood Pb2+ levels which are environmentally relevant and suggest that chronic Pb2+ exposure during development can influence the NMDA receptor complex in the adult rat brain.

Inhibition of long-term potentiation in developing rat visual cortex but not hippocampus by in utero exposure to polychlorinated biphenyls

The neurotoxic potential of polychlorinated biphenyls (PCBs) depends on the structure of the congener as well as on the age of the exposure. We exposed rats prenatally to a coplanar congener (PCB-77) or to a non-coplanar congener (PCB-47) and measured the amount of long-term potentiation (LTP) at postnatal days 11-19 in the visual cortex and hippocampus. While PCB-77 exposure affected LTP statistically significantly in cortical but not hippocampal slices, the exposure to PCB-47 was much less effective.

Synaptic plasticity in the CA1 and CA3 hippocampal region of pre- and postnatally lead-exposed rats.

The effects of low level lead exposure on synaptic plasticity in hippocampal regions CA1 and CA3 were determined in adult rats in vitro. In the CA3 region the NMDA (N-methyl-D-aspartate)-independent mossy fiber-CA3 synapse potentiation was not influenced by chronic pre- and postnatal lead exposure, while in the same rats, in the CA1 region the NMDA-dependent long-term potentiation was slightly reduced as compared to controls. Paired-pulse facilitation was neither impaired in CA1 nor in CA3 region in the lead-exposed rats. These findings suggest that NMDA-dependent forms of synaptic plasticity are more susceptible to chronic low level lead exposure than NMDA-independent forms of potentiation or paired-pulse facilitation.

Acute lead exposure transiently inhibits hippocampal neuronal activities in vitro.

The effects of acute lead exposure on extracellularly recorded evoked responses in the CA1 region of hippocampal slices were investigated. Field potentials in response to paired-pulse stimulation were assessed while perfusing the slices with normal media and media containing lead in concentrations of 0.2 microM to 53 microM. The evoked population excitatory postsynaptic potentials decreased during lead exposure to a lesser extent than the orthodromically evoked population spike, whereas the presynaptic fiber volley remained unchanged. The maximal inhibition of the orthodromically evoked responses depended strongly on the lead concentration. The input-output relations of the orthodromic responses obtained during perfusion with lead significantly differed from those during control conditions. The somatic short-term potentiation obtained by paired-pulse stimulation increased during the lead exposure. Lead seemed to inhibit the evoked activities only transiently: within 20 min after lead onset, the recorded responses had reached the control level again in spite of further lead perfusion. In contrast to the orthodromically evoked responses, the antidromically evoked population spikes remained constant at all concentrations used. It is concluded from these results that lead acts presynaptically in the hippocampal slice preparation. Additionally, lead interferes with non-synaptic processes at the pyramidal neurons in the CA1. Possible influences of lead over different neurotransmitter systems are discussed.

Postnatal development of synaptic plasticity in the CA3 hippocampal region of control and lead-exposed Wistar rats

The object of this study was to compare the postnatal development of mossy fiber potentiation (MFP) and paired-pulse facilitation in the CA3 region of control and led-exposed rats. The postnatal development of MFP was not influenced by the chronic pre- and postnatal lead exposure nor did we find a statistically significant impairment of MFP in region CA3 following lead exposure in the four age groups studied. In contrast to the adult animals, in the three immature groups of the control as well as the lead-exposed animals MFP was preceded by a posttetanic depression after which MFP developed slowly. The results of the paired-pulse procedure depended both on the age and on the interstimulus interval (ISI) in control and lead-exposed animals. The differences between control and lead-exposed rats were statistically significant only in the adult animals at an ISI of 10 ms. In this case paired-pulse stimulation resulted in an increase of the second evoked response relative to the first response in the lead-exposed animals while the same procedure decreased the second evoked response in the control animals. It is concluded that although low lead exposure had no effect on the expression of MFP in hippocampal CA3 region, inhibitory mechanisms as revealed by paired-pulse stimulation are impaired by lead in adult rats.