Biomedical subjects

L Altmann

Publications and source records attributed to L Altmann.

At least 19 recordsLinked to original sources

PubMed2001

Developmental exposure of rats to a reconstituted PCB mixture or aroclor 1254: effects on long-term potentiation and [3H]MK-801 binding in occipital cortex and hippocampus.

The central nervous system is one of the target organs for polychlorinated biphenyls (PCBs). We measured the effects of maternal exposure of Long-Evans rats to a mixture of PCB congeners reconstituted according to the pattern found in human breast milk (reconstituted mixture, RM) on long-term potentiation (LTP) in two brain regions. Exposure of the dams via food started 50 days prior to mating and was terminated at birth. In the first experiment, adult male and female offspring were exposed maternally to 40 mg/kg of the RM or the commercial mixture Aroclor 1254 (A1254). LTP and paired-pulse inhibition were measured in slices of the visual cortex. In addition, the binding of [3H]MK-801 to the N-methyl-D-aspartate (NMDA) receptor-ion channel as well as the [3H]muscimol binding to the GABA-A receptor in membrane preparations from the occipital cortex and hippocampus were determined. LTP as well as [3H]MK-801 binding were significantly reduced in the cortex following PCB exposure, while [3H]MK-801 binding in the hippocampus was not affected. In a succeeding experiment, LTP was determined in cortical and hippocampal slices from rats at postnatal days 10 to 20, following exposure to 0, 5, or 40 mg/kg of the RM. Cortical LTP was significantly affected by the RM while no effects were seen in hippocampal LTP. Taking the two experiments together, PCB exposure significantly reduced LTP, as well as [3H]MK-801 binding, in the cortex and had no effect in the hippocampus. The LTP deficits can only partly be related to the reduction of binding sites to the NMDA receptor; other PCB-induced neurochemical changes have to be assumed.

Administration, Oral↗

PubMed1998

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.

Aging↗

PubMed1998

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.

Animals↗

PubMed1997

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.

Age Factors↗

PubMed1997

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.

Child↗

PubMed1995

Maternal exposure to polychlorinated biphenyls inhibits long-term potentiation in the visual cortex of adult rats.

Rats were exposed prenatally to the coplanar congener 3,3',4,4'-tetrachlorobiphenyl (TCB). The amount of long-term potentiation (LTP) was measured in slices from the visual cortex and hippocampus of the adult males as well as of controls. While in the cortical slices from the controls a stable LTP could be induced, LTP was inhibited in the TCB-exposed rats. In hippocampal slices, the amount of LTP was not significantly different between the two groups. Our results suggest that the visual cortex of adult animals is functionally altered by TCB if the exposure takes place during embryonic development.

Animals↗

PubMed1995

Neurobehavioral and neurophysiological outcome of chronic low-level tetrachloroethene exposure measured in neighborhoods of dry cleaning shops.

The effects of chronic low-level tetrachloroethene (TCE) exposure on functions of the central nervous system (CNS) were measured in subjects living in the neighborhood of dry cleaning shops with a mean residential time of 10.6 years. Neurobehavioral tests were performed using a German version of the NES battery. Additionally, a pattern reversal visual-evoked potentials (VEPs) were recorded. the mean blood TCE concentration in the subjects was 17.8 micrograms/liter and the median indoor TCE air concentration measured in the residences was 1.36 mg/m3. The outcome of the NES subtests for vigilance, simple reaction time, as well as visual memory differed statistically significantly between the exposed subjects and the controls, whereas for VEP latencies the differences were statistically not significant. It is concluded that despite the low exposure levels, CNS functions might be affected by TCE in subjects living close to a dry cleaning facility if the exposure lasts for several years.

Adult↗

PubMed1994

Effects of maternal lead exposure on functional plasticity in the visual cortex and hippocampus of immature rats.

We examined the amount of long-term potentiation (LTP) in slices from the visual cortex and hippocampus of pre- and postnatally lead-exposed rats and controls at postnatal days (PND) 12-20. A dietary lead intake of 750 ppm by the dams resulted in a mean blood lead concentration in the suckling offspring of about 17' micrograms/dl. While high-frequency stimulation (HFS) of the white matter induced LTP of the field potentials in layers II/III in cortical slices of ten out of the 14 control rats, only three of the twelve lead-exposed rats showed a small amount of LTP. However, in slices from seven of the twelve lead-exposed rats a long-term depression was found following HFS. Furthermore, paired-pulse inhibition was weaker in cortical slices from the lead-exposed as compared to the control rats. In the CA1 hippocampal region the amount of LTP was significantly reduced in the lead-exposed group only in slices taken from rats at PND 16-20, while no differences were seen in slices from younger animals. It is concluded that even low level lead exposure impairs functions of the visual cortex in the immature rat. We suggest that the developing hippocampus is able to compensate for lead-induced functional deficits in the 2nd postnatal week, being more vulnerable at older ages.

Animals↗

PubMed1994

Neurophysiological aspects of hippocampal neurotoxicity.

Identification and analysis of chemical neurotoxicity in the central nervous system deals with synaptic transmission and plasticity. The hippocampus slice technique rendered a powerful tool for electrophysiological analysis of these events as modulated by neurotoxic chemicals. It does not only allow the detection of potentially harmful compounds, but also the elucidation of their mechanism of action. This might render it possible to analyze the risk of neurotoxic chemicals on the basis of quantitative data.

Animals↗

PubMed1994

Effects of chronic low level lead exposure on the expression of GFAP and vimentin mRNA in the rat brain hippocampus analysed by in situ hybridization.

In this study we used in situ hybridization to examine the effects of chronic low level lead toxicity during different periods of brain development. Low level lead is known to affect astroglia. GFAP and Vimentin were chosen as glialtypic markers for neurotoxicity. The effects of lead were investigated on male Wistar rats. Animals were divided into four groups: a control group, a permanent group exposed during gestation, lactation and post-weaning (E0-P100), a perinatal group exposed during gestation and postnatally until weaning (E0-P16), and a post-weaning exposed group (P16-P100). All experimental animals were fed a diet containing 750 ppm lead acetate. With respect to Vimentin mRNA no major differences could be detected among the treatment groups. Significant differences in GFAP mRNA levels were detected in the post-weaning group relative to controls. In this group we observed a strong increase of GFAP mRNA in the polymorphic zone of the dentate gyrus and in the CA1 region of the hippocampus. Permanent and perinatal groups showed no overt changes compared to controls. Our findings suggest that an irritation of the mature astrocyte results in a change from the quiescent to the reactive state. The majority of astrocytes that have been exposed during their development and differentiation fail to react even if the exposure is continued to adulthood. This suggests an irreversible insult by low level lead exposure during this period of time.

Animals↗

PubMed1994

Neurobehavioral and neurophysiological observations in six year old children with low lead levels in East and West Germany.

Within a larger comparative environmental health screening program in East and West Germany neurobehavioral and neurophysiological measures were taken in 367 six year old children in Leipzig (N = 179), Gardelegen (N = 68), and Duisburg (N = 120). Lead concentrations from venous blood samples (PbB) and from deciduous teeth (PbT) were measured as markers of environmental lead exposure by electrothermal AAS. Dependent variables included four subtests from NES1 (tapping, reaction time, pattern comparison, and Benton visual retention), as well as VEP-latencies (N2, P100, N3) evoked by checkerboard patterns of different size and contrast. The overall median blood lead-concentration was 5 micrograms/dl (range: 1.3-19.0 micrograms/dl), and the corresponding tooth lead-concentration was 2 micrograms/g (0.2-14 micrograms/g). The 95-percentile of the overall frequency distribution for PbB was below 10 micrograms/dl. Associations between markers of lead-exposure and neurobehavioral or neurophysiological outcome were assessed by means of multiple linear or logistic regression analyses. After adjusting for relevant confounders/covariates significant (p < 0.05) Pb-related deficit was found for tapping and pattern recognition with respect to PbB but not PbT. No such associations could be established for VEP-latencies. These results are compatible with the hypothesis that subtle neurobehavioral dysfunction in children may be associated with very low PbB.

Child↗

PubMed1993

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.

Animals↗

PubMed1993

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.

Animals↗

PubMed1991

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.

Animals↗

PubMed1990

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

The 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.

Adult↗

PubMed1988

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.

Action Potentials↗

PubMed1987

Functional and neuronal binocularity in kittens raised with rapidly alternating monocular occlusion.

1. In order to determine the degree of synchrony of binocular activation required for the development of binocularity we reared 11 kittens with rapidly alternating monocular occlusion. Alternating occlusion was achieved with microprocessor-controlled electrooptic solid-state shutters, which were fitted to individually moulded goggles. The intervals of alternating occlusion were varied from 50 to 1,000 ms. Two normally reared kittens and three kittens that were reared with the shutters operating synchronously with open/close intervals of 50/50 ms, 200/200 ms, and 400/100 ms, respectively, were used as controls. Toward the end of the critical period we examined the kittens' ability for binocular depth discrimination and tested binocular luminance summation of the pupillary light reflex. Single-cell recordings were made from the visual cortex in order to determine the percentages of binocularly excitable neurons. 2. There was a good correlation between the degree of asynchrony of binocular experience, the impairment of depth discrimination, and the percentage of binocular neurons. Kittens reared with alternation rates of 200, 330, and 400 ms, respectively, had developed normal binocularity and were indistinguishable from the controls. Alternation rates of 500 ms or longer prevented the development of normal depth discrimination and luminance summation and resulted in reduced cortical binocularity. 3. A linear relationship between depth discrimination, binocular luminance summation, and percentages of binocular neurons was found. 4. Our findings indicate that an asynchrony of binocular activation of several hundred milliseconds is compatible with the development of normal binocularity in the kitten visual system.

Animals↗

PubMed1987

Binocular luminance summation in young kittens and adult strabismic cats.

Normal adult cats show a 35% increase in pupil diameter when one eye is illuminated and the other occluded, rather than when both eyes are illuminated. Young kittens show significantly less binocular luminance summation than adult cats (14%). Since these kittens also show a significantly reduced pupillary response to luminance decrements, the postnatal development of binocular luminance summation reflects an increase in pupillary motility, rather than a development of binocular function. Binocular luminance summation is much reduced in esotropic cats (6%), but not in exotropic cats (33%). This finding casts doubts on the usefulness of binocular luminance summation as a measure of binocular function.

Aging↗