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H P Lipp

Publications and source records attributed to H P Lipp.

At least 19 recordsLinked to original sources
PubMed1992

Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein.

PrPC is a host protein anchored to the outer surface of neurons and to a lesser extent of lymphocytes and other cells. The transmissible agent (prion) responsible for scrapie is believed to be a modified form of PrPC. Mice homozygous for disrupted PrP genes have been generated. Surprisingly, they develop and behave normally for at least seven months, and no immunological defects are apparent. It is now feasible to determine whether mice devoid of PrPC can propagate prions and are susceptible to scrapie pathogenesis.

Aging↗
PubMed1992

Assessment of biological activities of mixtures of polychlorinated dibenzo-p-dioxins (PCDDs) and their constituents in human HepG2 cells.

Dose-response curves of the induction of P4501A1-dependent 7-ethoxyresorufin O-deethylase (EROD) were analyzed in human hepatoma HepG2 cells treated with defined mixtures of polychlorinated dibenzo-p-dioxins (PCDDs) and their 2,3,7,8-substituted constituents, similar to previous studies with rat hepatocytes and H4IIE cells (Schrenk et al. 1991). PCDDs appear to act less potent in human HepG2 cells in comparison with rat cells. For example, EC50 values of 2,3,7,8-Cl4DD were 8-fold and 19-fold higher than in rat H4IIE cells and hepatocytes, respectively. EC50 values of PCDDs were compared with that of 2,3,7,8-Cl4DD and expressed as 2,3,7,8-Cl4DD equivalents (TEs). Although the rank order of PCDD potencies was similar, TEs for some PCDDs (1,2,3,7,8-Cl5DD; TE = 0.75 and 1,2,3,7,8-Cl6DD; TE = 0.61) were found to be higher than in the rat system. In contrast to rat cells no significant induction of EROD could be detected with Cl8DD in HepG2 cells up to its limit of solubility. Experimentally determined TEs of PCDD mixtures containing 49 constituents were found to be largely due to additive effects of their 2,3,7,8-substituted constituents.

Animals↗
PubMed1992

A new computer program for detailed off-line analysis of swimming navigation in the Morris water maze.

The program TRACK-ANALYZER runs on AT-compatible microcomputers and performs off-line analysis of data recorded from Morris water-maze experiments by means of a video tracking system or digitizing tablet. Raw data must be available on disk as ASCII-files listing position coordinates sampled at a constant frequency. Automatic recognition and correction of artifacts and missing data is a key feature of the program, as well as the option to combine commands to user-defined macros. TRACK-ANALYZER offers maximal flexibility regarding experimental schedule, maze geometry and recording parameters and may also be used to analyze open-field activity. In addition to calculating basic parameters of the swim path, such as path length and time, the program counts crossings and hits of goal platform and four virtual reference annuli, calculates search times in five different maze fields, determines directionality, tortuosity and turning preferences of swimming behavior and allows the viewing of any number of trials simultaneously on screen. ASCII-formated data output may easily be exported to commercial statistics and graphics software.

Animals↗
PubMed1992

2,3,7,8-Tetrachlorodibenzo-p-dioxin and ethinylestradiol as co-mitogens in cultured rat hepatocytes.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) acts as a potent liver tumor promoter in female but not in male rats. As a basis for studying mechanisms of growth control by liver tumor promoters, the effects of TCDD, of two congeners and ethinylestradiol have been examined in primary cultures of hepatocytes. The agents alone were relatively ineffective but acted as co-mitogens when DNA synthesis was stimulated by epidermal growth factor (EGF). The co-mitogenic effect of TCDD was only observed in adult animals, which are less sensitive to EGF than juvenile animals. Similar effects were seen with two TCDD congeners (1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin and octachlorodibenzo-p-dioxin) in the rank order of their affinity to the Ah receptor. The concentration maximum required for their co-mitogenic action (3 x 10(-12) M for TCDD) was lower than that required for enzyme induction. TCDD was not able to overcome the inhibitory action of TGF-beta (1 ng/ml). Ethinylestradiol additively or even synergistically increased the effect of TCDD. The results suggest: (i) co-mitogenic actions of TCDD and congeners are mediated by the Ah receptor. They are elicited at lower concentrations than those required for the induction of drug-metabolizing enzymes. (ii) Estrogens enhance the co-mitogenic actions of dioxins.

Age Factors↗
PubMed1991

Weak or missing paw lateralization in a mouse strain (I/LnJ) with congenital absence of the corpus callosum.

Ward et al. (Brain Research 424 (1987) 84-88) have reported that reduced size of the corpus callosum (CC) was associated with a lower degree of paw preference in the mouse strain 129/J but not in the strain BALB/cCF. Both strains show individually different degrees of development of the CC but mice completely lacking CC occur rarely. The mouse strain I/LnJ shows complete agenesis of the CC. Thus, we have compared the degree of paw lateralization by means of a food reaching task in two samples of I/LnJ mice (n1 = 81, n2 = 93) with that of two common mouse strains which show a normal CC (C57BL/6JIbm, n = 44; DBA/2JZur, n = 48). The two samples of I/LnJ mice were tested in different laboratories. The first sample of I/LnJ mice had a mean age of 36 weeks. As compared to the control mice, the males but not the females showed a significantly reduced degree of paw preference. Both, callosal and acallosal mice showed a preference for left choices. The replication sample of I/LnJ mice contained only animals between 6 and 8 weeks old. All of them were ambilateral. There was no side preference and no gender difference. We conclude that congenital absence of the CC is a factor which may substantially interfere with the development of paw lateralization. However, depending on age and gender, about half of the acallosal mice develop a paw preference.

Agenesis of Corpus Callosum↗
PubMed1991

A computer-controlled Y-maze for the analysis of vibrissotactile discrimination learning in mice.

An automatized, computer-controlled Y-maze is described in which mice are trained to discriminate between two vibrissotactile, and/or visual stimuli, other modalities or combinations of modalities being testable as well. Movements of the mouse are recorded by photocells and monitored on a computer screen. Forward passage of the mouse is ensured by movable gates, and, if necessary, by brief air blows. Wrong choices are punished by air blows as well. The controller is a Hewlett-Packard Series 80 microcomputer with a 16 channel parallel input/output interface; programs are in BASIC. The program analyzes start latency, decision and homing time, side preference, inspections and ultimate choice, as well as choice strategies based on discrimination, left/right habits and short-term memory. Thus we can determine the nature of discrimination errors, and establish individual behavioral profiles of the animals. Results are both printed alphanumerically and plotted. The apparatus may be used for studying sensory physiology as well as cerebral lateralization, and drug or gene effects on memory and learning.

Anesthesia↗
PubMed1991

Swimming navigation and structural variations of the infrapyramidal mossy fibers in the hippocampus of the mouse.

The extent of the infrapyramidal mossy fiber projection in CA3 (IIP-MF) at the midseptotemporal level correlates negatively with two-way avoidance learning and positively with performance in the radial maze, both tasks known to be sensitive to hippocampal lesions. If hippocampal structural variations are causing behavioral variations, one must predict positive correlations between the extent of the IIP-MF and performance in swimming navigation. Thus, the authors studied learning and reversal learning of swimming navigation in mice in which the size of the IIP-MF had been randomized by means of systematic crosses and in 2 mouse strains known for differential infrapyramidal projections (C57BL/6 and DBA/2). In 19 random-bred mice (9 male, 10 female), the extent of the IIP-MF showed negative correlations with swimming time after platform reversal (day 4: r = -0.50, P < .03; day 5 r = -0.73, P < .001), but none during acquisition of the task. In addition, statistical analysis suggested an influence of asymmetrically distributed mossy fiber projections during reversal learning. The strain comparison between 18 DBA/2 and 16 C57BL/6 male mice confirmed these results: no strain difference during days 1-3, and a significantly faster swimming time in the strain C57BL/6 (with large IIP-MF) at day 5 (second day of reversal), associated with significantly more crossings of the former platform location during the early phases of reversal learning. This latter measure was also negatively correlated with asymmetry of the IIP-MF in both strains. Finally, variations of the IIP-MF were correlated partially with adjustment of swimming speed that appeared to depend on size and asymmetry of CA4 as well. Thus, natural variations in the size of the IIP-MF distribution, and, perhaps, of CA4, appear to linearly influence processes directly involved in complex spatial learning.

Animals↗
PubMed1991

Assessment of biological activities of mixtures of polychlorinated dibenzo-p-dioxins: comparison between defined mixtures and their constituents.

As a first step to assess biological activities of complex mixtures of polychlorinated dibenzo-p-dioxins (PCDDs), induction of 7-ethoxyresorufin O-deethylase (EROD) by defined mixtures and their constituents has been analysed in vitro. Two cell systems have been compared: primary hepatocyte cultures and hepatoma H4IIE cells. EC50 values of PCDDs were compared with that of the most potent compound, 2,3,7,8-Cl4DD (2,3,7,8-tetrachlorodibenzo-p-dioxin) and expressed as 2,3,7,8-Cl4DD equivalents (TEs). TEs for three defined mixtures containing up to 49 PCDDs could be predicted from the sum of TEs for the 2,3,7,8-substituted congeners. Efficacies (maximal enzyme induction) of less potent PCDDs (1,2,3,4-Cl4DD, Cl8DD and of a mixture containing 86% Cl8DD and of benz(a)anthracene were lower in hepatocytes (by 33%) and in H4IIE cells (by 50%). The results suggest that biological activities of complex PCDD mixtures are largely due to additive effects of their 2,3,7,8-substituted constituents.

Animals↗
PubMed1991

Early postnatal hyperthyroidism alters hippocampal circuitry and improves radial-maze learning in adult mice.

Inbred mice show strain-specific differences in the hippocampal mossy fiber projection. These differences are most pronounced in the portion of the projection that forms synaptic connections with the basal dendrites of the CA3 pyramidal neurons [intra- and infrapyramidal mossy fiber (IIP-MF) projection]. We have previously demonstrated that the extent of the IIP-MF subfield is positively correlated with the capacity to perform a spatial radial-maze task and that an experimentally induced enlargement of the IIP-MFs, by means of postnatal thyroxine treatment, predicted the ability of adult two-way avoidance learning. In the present study, we tested whether this treatment would also influence radial-maze performance. Forty-five male mouse pups from the inbred strain DBA/2 (chosen because of scanty IIP-MF projection and poor radial-maze learning) were divided into three groups that received daily injections of either 2 micrograms L-thyroxine, an alkaline vehicle solution, or physiological saline. Treatment lasted from postnatal days 0 to 11. At the age of 3 months, these animals were tested in an eight-arm radial maze. The extent of their IIP-MF projections was measured by means of planimetry on Timm-stained sections. Thyroxine-treated animals made significantly fewer errors and had larger IIP-MF projections as compared to both control groups. Within each group, the individual variability of the IIP-MF projection was significantly and positively correlated with performance. We conclude that experimentally modified IIP-MF projections mediate processes underlying spatial working memory. It would appear that the hippocampal circuitry alterations induced by postnatal hyperthyroidism can counteract a hereditary lack of talent, albeit only partially and in selected populations.

Animals↗
PubMed1990

Induction of drug-metabolizing enzymes by xenobiotics.

1. Isozymes of the cytochromes P-450, UDP-glucuronosyl transferases (UDPGT) and glutathione S-transferases appear to be differentially inducible by prototype inducers, such as 3-methylcholanthrene (MC), phenobarbital, pregnenolone 16 alpha-carbonitrile and clofibrate. 2. Mechanisms of induction include both transcriptional and post-transcriptional control. MC-type inducers (representing a large number of planar polycyclic aromatics, beta-naphthoflavone and polyhalogenated aromatics) bind with high affinity to the Ah receptor which controls gene expression similar to steroid hormone receptors. The Ah receptor controls the expression of several drug metabolizing enzymes. For example, both cytochrome P450 IA1 and UDPGT-1 appear to be co-induced by inducers with widely differing potencies, such as 2,3,7,8-tetrachloro-dibenzo-p-dioxin, 1,2,3,7,8-pentachloro-dibenzo-p-dioxin and benz(a)anthracene. Much less is known about the mechanism of action of other inducer prototypes. 3. Induction and co-induction of drug-metabolizing enzymes are generally considered as adaptive responses leading to more efficient elimination and detoxication of xenobiotics such as benzo(a)pyrene. For example, when the mutagenicity of benzo(a)pyrene and benzo(a)pyrene-3,6-quinone was studied in the Ames test, glucuronidation or glutathione conjugation (concomitant with cytochrome P-450-dependent reactions) markedly decreased their mutagenicity. The protective effect was more pronounced with the homogenate S9 fraction of MC-treated rats. However, at 'non-physiological' levels of exposure enzyme induction may lead to increased toxic risk.

Animals↗
PubMed1989

Using genetically-defined rodent strains for the identification of hippocampal traits relevant for two-way avoidance behavior: a non-invasive approach.

Genetically-defined rodent strains permit the identification of hippocampal traits which are of functional relevance for the performance of two-way avoidance behavior. This is exemplified here by analyzing the relationship between infrapyramidal mossy fibers (a tiny projection terminating upon the basal dendrites of hippocampal pyramidal neurons) and two-way avoidance learning in about 800 animals. The necessary steps include 1) identification of structural traits sensitive to selective breeding for extremes in two-way avoidance, 2) testing the robustness of the associations found by studying individual and genetical correlations between hippocampal traits and behavior, 3) establishing causal relationships by Mendelian crossing of strains with extreme structural traits and studying the behavioral consequences of such structural 'randomization', 4) confirming causal relationships by manipulating the structural variable in inbred (isogenic) strains, thereby eliminating the possibility of genetic linkage, and 5) ruling out the possibility of spurious associations by studying the correlations between the hippocampal trait and other behaviors known to depend on hippocampal functioning. In comparison with the classical lesion approach for identifying relationships between brain and behavior, the present procedure appears to be superior in two aspects: it is non-invasive, and it focuses automatically on those brain traits which are used by natural selection to shape behaviorally-defined animal populations, i.e., it reveals the natural regulators of behavior.

Animals↗
PubMed1989

Renal mesangium is a target for calcitonin gene-related peptide.

Rat calcitonin gene-related peptide (CGRP alpha; EC50, 1 nM) was shown to stimulate cAMP formation in cultured rat renal mesangial cells. CGRP concentration dependently (EC50, 1 nM) also inhibited contraction of mesangial cells by angiotensin II (10 nM). Angiotensin II (10 nM) caused a transient increase of the intracellular calcium concentration from 140 nM to 480 nM in the mesangial cells, but these calcium transients were not altered by CGRP. CGRP (10 nM) decreased vascular resistance in the isolated rat kidney perfused at constant pressure (100 mm Hg; P less than 0.01). The decreased vascular resistance was accompanied by a rise of the glomerular filtration fraction. CGRP, moreover, attenuated the effects of angiotensin II on renal vascular resistance and glomerular filtration (P less than 0.01). In conclusion, CGRP causes relaxation of renal mesangial cells and decreases renal vascular resistance. As a result CGRP raises glomerular filtration and the filtration fraction. The effect may be linked to cyclic AMP formation. Thus, regulation of renal vascular and glomerular function may represent a novel action of CGRP apart from its cardiovascular effects.

Angiotensin II↗
PubMed1988

Infrapyramidal mossy fibers and two-way avoidance learning: developmental modification of hippocampal circuitry and adult behavior of rats and mice.

The extent of the intra- and infrapyramidal mossy fiber projection (IIP-MF) in the hippocampus of mice and rats is strain-specific, and correlates negatively with the strain-specific capacity of avoidance learning. If variations of the IIP-MF influence the capacity for 2-way avoidance learning, then developmental modification of the IIP-MF projection in an individual member of a strain should remain correlated with its adult behavior. Pups of strains with high avoidance capacity and small IIP-MF projections (RHA rats, DBA/2 and BALB/c mice) were injected with varying doses of thyroxine during the postnatal period. This transient hyperthyroidism resulted in a strong, yet largely unpredictable, variability of the IIP-MF projection in the adult animals. Furthermore, postnatal saline injections also increased the variability of the IIP-MF projection; however, this was to a lesser degree than when using thyroxine. The animals were tested for 2-way avoidance learning at the age of 90-120 d. Many showed strain-atypical avoidance scores. These deviations from the inherited level of 2-way avoidance learning were strongly correlated with the magnitude of the IIP-MF projection, regardless of whether the structural changes resulted from thyroxine or saline injections. A multivariate analysis showed that the observed correlations could neither be explained by thyroxine-induced changes in brain weight nor by individual differences of other terminal fields in the hippocampal region CA3. These results suggest that the extent of the IIP-MF projection is influenced by several genetic and epigenetic factors. Irrespective of the underlying causes, the magnitude of the IIP-MF (or of an unknown but well-correlated variable) appears to bias the adult capacity for 2-way avoidance learning predictably.

Animals↗
PubMed1987

Radial-maze performance and structural variation of the hippocampus in mice: a correlation with mossy fibre distribution.

Twenty-four male mice, belonging to 8 different inbred strains, were tested in an 8-arm radial maze. Clear strain differences were found for performance on the third day of training, which correlated very strongly with the size of the hippocampal intra- and infrapy ramidal mossy fibre (iip-MF) terminal fields. These results, combined with those from earlier experiments, indicate that genetic variations of the iip-MF projection influence processes that determine behavioural abilities of mice.

Animals↗
PubMed1987

Strain-specific correlations between hippocampal structural traits and habituation in a spatial novelty situation.

The rat strains Naples high-excitable (NHE) and Naples low-excitable (NLE) have been selectively bred since 1976 for behavioral arousal in a spatial novelty situation. The Timm-stained hippocampi of 20 NHE and 18 NLE rats were examined morphometrically for differences in the proportions (volume percentages) of terminal fields in the fascia dentata and CA3/CA4 at the mid-septotemporal level. Prior to histology animals were tested on 2 days for exploratory activity in a square alley system (Làt box). Overall, the two strains differed significantly in the percentage of stratum lacunosum molecular (NHE greater than NLE, P less than 0.001), of the intra/infrapyramidal mossy fiber (IIP-MF) projection (NLE greater than NHE, P less than 0.001), of the granule cell layer (NLE greater than NHE, P less than 0.05) and of the outer molecular layer (NHE greater than NLE, P less than 0.05). Both strains had an IIP-MF projection smaller than in any other rat strain. Most of the strain differences, however, appear to reflect genetic drift rather than a response to selective breeding. Unexpectedly, the highly active line (NHE) showed a strong correlation between the IIP-MF and overnight habituation; the larger the IIP-MF projection, the lesser the long-term habituation (r = -0.70, P less than 0.001). In the NLE rats, the IIP-MF correlated positively with overnight habituation (though not significantly, because of an outlier). In both lines, stratum oriens was negatively correlated with short-term habituation in the second exposure (NHE: r = -0.68, P less than 0.001; NLE: r = -0.66, P less than 0.01). Thus, hippocampal variability of non-genetic origin appears to be correlated with processes which modulate strain-characteristic responses to a spatial novelty situation.

Animals↗
PubMed1978

Aggression and flight behaviour of the marmoset monkey Callithrix jacchus: an ethogram for brain stimulation studies.

The aggressive and flight behaviour of the common marmoset monkey (Callithrix jacchus) is described and split into behavioural units, allowing analysis of agonistic behaviour evoked by electrical stimulation of the hypothalamus. The social context of the described units is also considered. C. jacchus shows clearly recognizable behavioural patterns. Free-born animals are very timid and show typical flight reactions. Within aggressive behaviour, two types of aggression can be distinguished: very violent attacks causing severe injuries, often accompanied by particular threat displays and observed during dominance and territorial encounters, and, on the other hand, relatively harmless short attacks, together with a noisy vocalization, for defensive purposes or keeping group members at a distance.

Aggression↗