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Biomedical subjects

J H Lammers

Publications and source records attributed to J H Lammers.

11 recordsLinked to original sources

Multivariate time of peak effects assessment for use in selecting time of testing in acute neurotoxicity studies.

One of the aims of conducting observational assessments shortly following administration of a test compound is to provide information regarding the profile of acute neurotoxic effects. By limiting the time of peak effects (TOPE) determination to a time range-finding study using only gait and arousal as the end-points for determining time of peak effects, as was proposed in the IPCS/WHO Collaborative Study on Neurobehavioral Screening Methods protocol, it is possible that the time of testing selected for the acute study proper may underestimate other neurotoxic effects which show a different time course. We explored the feasibility of including measures of autonomic activity as well as clonic/tonic movements in the TOPE determination in two experiments using chlorpyrifos and carbaryl as test compounds. A scoring system based on the original operational definitions provided in the IPCS/WHO protocol was devised. Results indicated that there were considerable differences in the time course for autonomic effects and convulsive behavior in comparison to effects on gait and arousal. It is concluded that the use of a multivariate approach for TOPE determination may provide a more comprehensive empirical basis for selecting a testing time for studies designed to profile acute neurotoxic effects.

Animals↗

A change in the phosphorylation pattern of the 30000-33000 Mr synaptonemal complex proteins of the rat between early and mid-pachytene.

The lateral elements (LEs) of synaptonemal complexes (SCs) of the rat contain major components with relative electrophoretic mobilities (Mr s) of 30000-33000, which are the products of a single gene. After one-dimensional separation of SC proteins on polyacrylamide-SDS gels, these components show up as two major bands, whereas upon two-dimensional electrophoresis they are resolved in at least 24 spots, which focus at pH 6.5 to 9.5. In this paper we show that these spots represent phosphorylation variants. For the analysis of the phosphorylation of the 30000- to 33000-Mr SC components during progression through meiotic prophase, we developed a procedure for isolation of fractions of testicular cells of the rat that are enriched in separate stages of meiotic prophase. Analysis of the 30000- to 33000-Mr SC components in these fractions by two-dimensional electrophoresis and immunoblotting showed that phosphorylated variants of the 30000- to 33000-Mr SC proteins occur throughout meiotic prophase. However, the extent of phosphorylation changes between early and mid-pachytene, when one phosphate group is probably added to each of the variants.

Animals↗

The gene encoding a major component of the lateral elements of synaptonemal complexes of the rat is related to X-linked lymphocyte-regulated genes.

The lateral elements of synaptonemal complexes (SCs) of the rat contain major components with relative electrophoretic mobilities (M(r)S) of 30,000 and 33,000. After one-dimensional separation of SC proteins on polyacrylamide-sodium dodecyl sulfate gels, these components show up as two broad bands. These bands contain closely related proteins, as judged from their peptide maps and immunological reactivity. Using affinity-purified polyclonal anti-30,000- and anti-33,000-M(r) component antibodies, we isolated a cDNA encoding at least one of the 30,000- or 33,000-M(r) SC components. The protein predicted from the nucleotide sequence of the cDNA, called SCP3 (for synaptonemal complex protein 3), has a molecular mass of 29.7 kDa and a pI value of 9.4. It has a potential nucleotide binding site and contains stretches that are predicted to be capable of forming coiled-coil structures. In the male rat, the gene encoding SCP3 is transcribed exclusively in the testis. SCP3 has significant amino acid similarity to the pM1 protein, which is one of the predicted products of an X-linked lymphocyte-regulated gene family of the mouse: there are 63% amino acid sequence similarity and 35% amino acid identity between the SCP3 and pM1 proteins. However, SCP3 differs from pM1 in several respects, and whether the proteins fulfill related functions is still an open question.

Amino Acid Sequence↗

Interactions between simultaneously activated behavioral systems in the rat.

Interactions between electrically induced attack and teeth-chattering from 1 electrode and grooming from another were examined in male albino rats. The interaction between electrically induced attack and deprivation-induced feeding, as well as the effect of food deprivation on attack, was also studied. Results indicate that attack appears to be a dominant response, for it suppressed grooming and feeding at a low level of activation. On the other hand, it was not affected by simultaneously induced grooming or feeding. However, food deprivation decreased the threshold for attack, leaving attack latency, attack form, or bite targets unaffected. Teeth-chattering, suggested to be related to attack and flight, was also a dominant response. Results suggest that interactions between behavioral systems are in favor of the systems that must act acutely on activation in order to survive. Apparently, the regulations governing these interactions are represented in the functional organization of the brain.

Aggression↗

Hypothalamic substrates for brain stimulation-induced patterns of locomotion and escape jumps in the rat.

The hypothalamic response area for electrically induced locomotion was determined using moveable electrodes and discriminant analysis as an appropriate statistical technique. At 241 out of 641 stimulated sites locomotion was induced. The distribution of locomotion sites is relatively diffuse. Discriminant analysis of both positive and negative electrode localizations yields areas with high, intermediate or low probability of inducing the response. The response is considered to be mediated by fibres of the subpallido-pedunculopontine system, which includes the mesencephalic locomotor region. Different categories of exploratory and flight-directed locomotion were distinguished, and response areas for both categories were determined. In addition the response area for escape jumps was delimited. Exploratory locomotion is mainly induced from the lateral hypothalamus, while flight-directed locomotion and escape jumps are evoked from the medial hypothalamus. The response area for exploratory locomotion reflects the lateral hypothalamic distribution of the subpallidal projection to the mesencephalic locomotor region. A diffuse substrate for flight behavior seems to occupy almost the entire medial hypothalamus. It is concluded that a locomotor subroutine subserving different behavioural mechanisms can be activated at many hypothalamic sites.

Animals↗

Hypothalamic substrates for brain stimulation-induced attack, teeth-chattering and social grooming in the rat.

In this paper the boundaries of the hypothalamic response areas for brain stimulation-induced attack, social grooming and teeth-chattering were delimited. A total of 641 hypothalamic sites in 71 male CPW/WU Wistar rats were electrically stimulated. Positive sites for any behavioural response cluster into restricted hypothalamic areas. Discriminant analysis of both positive and negative electrode localizations yields areas with high, intermediate and low probabilities of inducing the behavioural response concerned. Each response has its own response area where probabilities are high. Neuroanatomical correlates of these response areas are discussed. The response area of attack is suggested to be an integrative processing area, stimulation of which overrules some aspects of integration and directly activates the behavioural program of attack. Although some authors consider all three responses to be part of the behavioural repertoire of aggression, the response areas are not identical. Social grooming and attack are considered to be induced from different neural systems. Similarly, attack and teeth-chattering have been shown to derive from different neural mechanisms, despite substantial overlap of both response areas. It is suggested that teeth-chattering derives from the simultaneous activation of both attack and flight tendencies. No further distinctions with respect to threshold current intensities can be made within responses areas. However, the underlying neural substrates are not homogeneous, for thresholds vary along the course of individual electrodes.

Aggression↗

Hypothalamic substrates for brain stimulation-induced grooming, digging and circling in the rat.

Despite a great number of studies concerned with the induction of specific behavioural responses from the rat hypothalamus by electrical brain stimulation, hypothalamic response areas and underlying neural substrates have never been determined accurately. In this study the boundaries of the hypothalamic response areas for grooming, digging and circling were delimited using moveable electrodes, an enriched environment containing a variety of goal objects, and an appropriate statistical technique. A total of 641 hypothalamic sites in 71 male CPB/WU Wistar rats were electrically stimulated. Results are plotted on a detailed stereotaxic brain atlas of the rat hypothalamus. Positive sites for any behavioural response cluster into restricted hypothalamic areas. Discriminant analysis of both positive and negative electrode localizations yields areas with high, intermediate or low probabilities of inducing the behavioural response concerned. Each response has its own response area where probabilities are high, although there may be overlap. Even within response areas a distinction can be made between areas in which the response can be induced at relatively high or low threshold current intensities. Lowest threshold sites within electrode tracks are often clustered. In search of neuroanatomical correlates, grooming is related to the distribution of ACTH-immunoreactive neural elements, digging is related to the distribution of efferent fibres from the bed nucleus of the stria terminalis, and circling is related to the distribution of dopaminergic fibres of the nigrostriatal pathway. The results clearly point to the stimulation site being the most important determinant of the evoked behavioural response. Evidently behavioural specificity does exist within the hypothalamus.

Animals↗

Postpartum aggression in rats does not influence threshold currents for EBS-induced aggression.

Female Wistar rats were tested for aggressive behaviour induced by electrical brain stimulation (EBS) in the lateral hypothalamus. Threshold currents for the induction of aggression were determined on several days before the females were paired with experienced breeder males. Beginning in the second week of pregnancy threshold current values were measured once or twice weekly. No change in thresholds was observed either during pregnancy, the early postpartum period or after weaning. Lactation was the only period during which the females were spontaneously aggressive towards male intruders in their home cage, but not in the EBS cage. Analysis of bite targets revealed no difference between the bite patterns in the postpartum maternal aggression test and the EBS-induced attacks. The results demonstrate that the change in physiological and hormonal status in pregnant and lactating females has no influence on the propensity to attack during EBS. The similarity in wound patterns does not advocate a major difference in the types of aggression studied. We speculate upon the nature of EBS-induced attacks as the activation of a rigid, final pathway of aggression which is rather insensitive to mild modulations.

Aggression↗

Mid-frequency hearing loss and reduction of acoustic startle responding in rats following trichloroethylene exposure.

Modification of auditory evoked startle responding using prepulse inhibition was used to examine the effects of trichloroethylene (TCE) exposure on auditory thresholds. Rats were exposed by inhalation to 0, 1500, or 3000 ppm TCE for 18 hours per day, 5 days a week for 3 weeks. Auditory thresholds for 5 and 20 kHz tones were measured before exposure and at 1, 3, and 6 weeks postexposure. In addition, hearing thresholds for 5 and 35 kHz tones were examined at a 5-week postexposure time-point. Results indicated that hearing thresholds for 20 kHz but not for 5 or 35 kHz prepulses were significantly increased in rats exposed to 3000 ppm TCE. These findings demonstrate a selective hearing loss in the 20 kHz range by short-term, high-level TCE exposure. With respect to effects on startle responding per se, the present study also found that compared to controls, TCE-exposed rats failed to show an increase in baseline startle with repeated testing. This difference could not be attributed to differences in body weight and was persistent throughout the postexposure period.

Acoustic Stimulation↗

Changes in regional brain GFAP levels and behavioral functioning following subchronic lead acetate exposure in adult rats.

Adult male WAG/Rij/MBL rats were dosed with lead acetate at 0, 4.0, 8.0 or 12.5 mg/kg, 5 days per week for 4 weeks. Animals were assessed prior to exposure, at the end of the 4-week exposure period and after a 2-week recovery period using a functional observational battery (FOB) and motor activity assessment. Rats were sacrificed two weeks after the last test session and glial fibrillary acidic protein (GFAP) concentrations were measured in eight selected brain regions. A dose-dependent decrease in motor activity was observed immediately following the end of the exposure period with no differences observed 2 weeks after cessation of exposure. Alterations in gait, decreased fore- and hindlimb grip strength, and decreased arousal were also found. Behavioral changes were accompanied by reduced weight gain and decreased body temperature during the course of exposure. GFAP concentrations were elevated in the frontal cortex, occipital cortex, striatum' and hippocampus but not in thalamus, cerebellum or brain stem. These results indicate that lead causes functional effects in the adult rat which can be detected by neurobehavioral methods. Furthermore, region-specific alterations in brain GFAP concentrations provided evidence of specificity of lead neurotoxicity in the adult brain.

Animals↗