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.

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.

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.

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.

Assessment of neurophysiologic and neurobehavioral effects of environmental pollutants in 5- and 6-year-old children.

To investigate the effects of environmental pollutants on neuronal functions in residents of different areas in Germany, a mobile laboratory was developed. The equipment permits the assessment of neurophysiologic as well as neurobehavioral parameters in epidemiologic studies. In two sets of field experiments in 1991 and 1994, more than 700 children, 5 and 6 years old, were tested in three different towns in East and West Germany. Visual functions were measured neurophysiologically by visually evoked potentials, using pattern reversal stimulation. By means of psychophysical methods, the contrast sensitivity was tested and the visual acuity assessed. Finger tapping, simple reaction time, vigilance, pattern comparison, pattern memory, and memory of geometric figures were measured using the Neurobehavioral Evaluation System (NES1 and NES2). In a preliminary analysis, the outcomes of the tests were related to the children's blood lead levels. The experiences with the field studies showed that all tests could be successfully performed even in pre-school-age children. The mobile laboratory has proven to be a useful tool for the detection of neurotoxic effects of environmental pollutants in larger populations, providing the opportunity for flexible operation at different locations.

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.

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.

Helicoidal peripapillary chorioretinal degeneration.

A family with helicoidal peripapillary chorioretinal degeneration is described. This is a rare bilateral fundus affection--only seven more or less typical cases have been reported in the literature. 21 patients from the same family in four generations were examined, 10 men and 11 women. Seven men and six women showed a helicoidal affection. Of this number, there were 11 children aged from 4-17 years, six were girls of whom three had helicoidal fundus and five were boys of whom two were affected. General examination revealed nothing of particular interest. We have here a congenital hereditary fundus anomaly or minor malformation in four generations--young people with normal visual acuity who develop with age a clear tendency to invasion of the macular region by a degenerative process. This is most dangerous for the visual acuity when the atropic helicoidal wings lie in or near the macula region.