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Dietrich E Lorke

Publications and source records attributed to Dietrich E Lorke.

10 recordsLinked to original sources
PubMed2006

Caspase-3 immunoreactivity in different cortical areas of young and aging macaque (Macaca mulatta) monkeys.

It has been shown that cytochrome-c-dependent caspase-3 activation is significantly elevated in the aging macaque brain. To assess the underlying age-related changes in the cellular distribution of caspase-3, we have examined the motor cortex, cerebellum and hippocampus of young (4-year-old, n = 4) and old (20-year-old, n = 4)rhesus monkeys by immunohistochemistry. Western blot analyses of brain homogenate showed that the antibody reacted only with inactive 32-kDa procaspase and its active 20- and 17-kDa subunits, formed after granzyme B exposure. In the motor cortex, pyramidal cells of layers III and V were moderately labeled; the underlying white matter contained weakly stained astrocytes. In the hippocampus, hilar neurons and pyramidal cells in CA3 showed the strongest immunoreaction, pyramidal cells in CA1 and granule cells of the dentate gyrus were also strongly labeled. In contrast, CA2 pyramidal cells were only weakly stained, and neurons of the molecular layer were unlabeled. Weak caspase-3 immunoreaction of CA2 neurons parallels known decreased susceptibility to apoptosis. In the cerebellar cortex, clusters of strongly labeled Purkinje cells were observed next to groups of weakly and unstained cells; granule cells were generally unstained. The brains of aging monkeys displayed a similar pattern of caspase-3 immunoreactivity. In neocortical layer V, however, scattered very strongly labeled pyramidal cells were regularly detected, which were not observed in younger animals. This clustering of caspase-3 indicates increased vulnerability of a subset of pyramidal cells in the aging brain.

Aging↗
PubMed2006

Serotonin 5-HT2A and 5-HT6 receptors in the prefrontal cortex of Alzheimer and normal aging patients.

BACKGROUND: It has been hypothesized that alterations of the serotonergic system contribute to neuropsychiatric symptoms in Alzheimer disease (AD). Cellular expressions of the two serotonergic receptors 5-HT2A and 5-HT6 have therefore been determined by immunohistochemistry in the prefrontal cortex of patients with AD (n=6) and normal age-matched controls (n = 7). RESULTS: In normal aging patients, 5-HT2A label was mainly observed in large pyramidal cells, but to a lesser extent also in small pyramidal cells and in stellate cells of cortical layers II-VI. In AD, a similar distribution was observed, but density of positive cells was significantly reduced by 33%. In aging control patients, the 5-HT6 receptor was expressed by pyramidal cells and occasional stellate cells, not only of layers II-V, but also of layer I, where a distinct label was observed in neurons and surrounding fibers. 5-HT6 receptor expression in AD patients had the same pattern, but was significantly decreased by 40%. CONCLUSION: Our results indicate that a decline in neurons expressing 5-HT2A, but also 5-HT6 receptors may play a role in the etiopathology of neuropsychiatric symptoms in AD.

Aged↗
PubMed2005

The pattern of c-fos activation in the CNS is related to behavior in the mudskipper, Periophthalmus cantonensis.

The effects of three types of behavior on c-fos activation in different brain regions of the mudskipper, Periophthalmus cantonensis, were studied by immunocytochemistry. Animals were divided into four groups: The control group did not undergo any specific treatment. The second group consisted of animals that were agitated for an hour with a glass rod at an irregular speed. The third group contained animals showing aggressive behavior during an hour of monitoring, i.e. documented territorial hostility by raising of dorsal fins and pursuit of intruders. In contrast to these three groups, which had last been fed 24h earlier, the fourth group included animals that had been nourished 1h prior to sacrifice. Results showed that, in most brain regions of control animals, there were relatively few c-fos positive cells. After fish had been agitated, however, very prominent c-fos label was seen in the lateral and medial parts of the telencephalon, the thalamus, hypothalamus, pituitary and medulla. In aggressive fish, a significant increase in the number of c-fos positive sites, as compared to control fish, was observed in the diencephalons, pons and medulla, but not in the telencephalon. After feeding, there was a less substantial increase in c-fos protein expression in the diencephalon, but an even more prominent c-fos activation in the pons and medulla. Our present results support the hypothesis that, in fish, the medial telencephalon is involved in avoidance reaction and the lateral telencephalon in spatial memory, whereas rhombencephalic activation may reflect activity of cranial nerve nuclei.

Aggression↗
PubMed2005

Postnatal changes in functional activities of the pig's brain: a combined functional magnetic resonance imaging and immunohistochemical study.

Developmental changes in brain activation after pain stimulation and after passive movement of the hind paw were assessed by functional magnetic resonance imaging (fMRI) in pigs of postnatal ages 2, 4 and 6 months. Response patterns were correlated with histological maturation parameters. At 2 months, fMRI failed to detect brain activation after pain stimulation and revealed weak, but widespread activation after passive movement. At 4 months, strong reaction of numerous cortical areas on the contralateral side was seen after pain stimulation. Following passive movement, activation was weaker but more widespread, and the brainstem was also involved. By 6 months, cortical activation became more restricted to the contralateral sensory cortex and brainstem after pain stimulation and to the contralateral sensory and ipsilateral premotor and motor cortices after passive movement. Neocortical synaptophysin immunoreaction increased significantly between 2 and 4 months and slightly decreased by 6 months. The density of GABA-immunoreactive neurons and fibers significantly increased, reaching a maximum at 6 months. Our studies indicate that remodeling of synapses and development of inhibitory GABA neurons last until 6 months postnatally, when the fMRI response of the pig's brain also attains its mature adult pattern.

Aging↗
PubMed2004

Age-related alterations in cytochrome c-mediated caspase activation in rhesus macaque monkey (Macaca mulatta) brains.

Age-related changes and regional differences in caspase expression were determined in the primate brain. Using immunoblot analysis, the levels of endogenous caspase-3, caspase-9 and cytochrome c-triggered activated caspase-3 were examined in brain homogenates from the prefrontal, motor and visual cortices, cerebellum, hippocampus and amygdala of 4-year-old and 20-year-old rhesus macaques. Procaspase-3 was detected in similar quantities in all brain regions of both young and aging macaques. Being found in all brain regions, caspase-9 was significantly elevated in old macaques as compared to young ones. After incubation with cytochrome c, active forms of caspase-3 were detected in all brain regions of young and old macaques. In almost all brain regions of old monkeys, the levels of cytochrome c-dependent caspase-3 activation were higher than those of young macaques. These results suggest that the aging rhesus macaque brain has a lower threshold to apoptotic stimuli.

Adenosine Triphosphate↗
PubMed2004

An optimized fixation and extraction technique for high resolution of inositol phosphate signals in rodent brain.

Members of lower and higher inositol phosphates distinctly participate in signal transduction (1). Relatively little is known regarding possible biological functions of inositol phosphates in functionally different areas of the intact brain. A detailed study on the regional distribution of biologically important inositol phosphates may help elucidate their physiological functions in different brain regions in the regional tissue context. We now show a novel technique which allows fixation and subsequent dissection of whole rat brains into small volume elements for mapping of the whole range of inositol phosphates from Ins(1,4,5)P3 to InsP6. The method has been successfully applied to investigate regional differences of a broader spectrum of inositol phosphates in microdissected brain tissue and to construct 3D-maps of these signaling compounds. The technique can be particularly well employed to investigate regional changes in the spectrum of higher inositol phosphates and phosphoinositides upon neuronal stimulation induced by motor activity or drug treatment.

Animals↗
PubMed2003

Nkx6.1 controls migration and axon pathfinding of cranial branchio-motoneurons.

As many studies have focused on the mechanisms of motoneuron specification, little is known about the factors that control the subsequent development of postmitotic motoneurons. Previously, we showed that the transcription factor Nkx6.1 is required for the early specification of somatic motoneuron progenitors in the spinal cord. Our present analysis of hindbrain motoneuron development in Nkx6.1-deficient mouse embryos reveals that the early specification of branchio-motoneurons is independent of Nkx6.1 function, but that it is required for their subsequent development. In Nkx6.1 mutant mice, we observed defects in the migration, as well as in the axon projections of branchio-motoneurons. A detailed analysis of the migratory defect in facial branchio-motoneurons reveals ectopic expression of the cell surface receptors Ret and Unc5h3 in premigratory neurons, but no changes in the rhombomeric environment. Taken together, our findings demonstrate a requirement for Nkx6.1 in the development of postmitotic motoneurons, and suggest a cell-autonomous function in the control of branchio-motoneuron migration.

Animals↗
PubMed2003

Development of catecholaminergic neurons in the human medulla oblongata.

Distribution and maturation of catecholaminergic (CA) neurons have been studied by tyrosine hydroxylase immunohistochemistry in the medulla oblongata of human fetuses aged 14.5-25 weeks of gestation. Already at 14.5 weeks, CA neurons were observed in two longitudinally oriented cell clusters, one located ventrolaterally in the area of the lateral reticular and ambiguous nuclei, the other one dorsomedially forming 4 groups related to the dorsal vagal nucleus, the commissural nucleus of the vagus, the nucleus of the tractus solitarius and the area postrema. CA neurons in the area postrema were often found close to blood vessels. Scattered intermediate CA neurons were seen between these two larger clusters. CA neurons still appeared immature exhibiting bipolar morphology with only one or two short stout processes, which hardly branched. At 21 weeks, CA neurons occupied essentially the same location, but had a more mature morphology. Though still bipolar in shape, they had thinner and much longer processes which frequently branched. Both in the ventrolateral and the dorsomedial cell clusters, these processes were frequently lying close to blood vessels. At 25 weeks, CA cells had matured into multipolar neurons with long thin processes forming fine fiber networks in the ventrolateral medulla as well as around and within the dorsal vagal and solitarius nuclei. Only at this stage, a distinct CA fiber tract was seen located in the region of the tractus solitarius. Our results indicate that CA neurons in the human medulla, which are presumably involved in the control of ventilation and blood pressure, though generated rather early during development, mature relatively late.

Adult↗
PubMed2002

Proliferation and apoptosis in the developing human neocortex.

The cell kinetics of the developing central nervous system (CNS) is determined by both proliferation and apoptosis. In the human neocortex at week 6 of gestation, proliferation is confined to the ventricular zone, where mitotic figures and nuclear immunoreactivity for proliferating cell nuclear antigen (PCNA) are detectable. Cell division is symmetric, with both daughter cells reentering mitosis. At week 7, the subventricular zone, a secondary proliferative zone, appears. It mainly gives rise to local circuit neurons and glial cells. Around week 12, the ventricular and subventricular zones are thickest, and the nuclear PCNA label is strongest, indicating that proliferation peaks at this stage. Thereafter, asymmetric division becomes the predominant mode of proliferation, with one daughter cell reentering mitosis and the other one migrating out. Towards late gestation, the ventricular and subventricular zones almost completely disappear and proliferation shifts towards the intermediate and subplate zones, where mainly glial cells are generated. A remnant of the subventricular zone with proliferative activity persists into adulthood. In general, proliferation follows a latero-medial gradient in the neocortex lasting longer in its lateral parts. Apoptotic nuclei have been detected around week 5, occurring in low numbers in the ventricular zone at this stage. Apoptotic cell death increases around midgestation and then spreads throughout all cortical layers, with most dying cells located in the ventricular and subventricular zones. This spatial distribution of apoptosis extends into late gestation. During the early postnatal period, most apoptotic cells are still located in the subcortical layers. During early embryonic development, proliferation and apoptosis are closely related, and are probably regulated by common regulators. In the late fetal and early postnatal periods, when proliferation has considerably declined in all cortical layers, apoptosis may occur in neurons whose sprouting axons do not find their targets.

Apoptosis↗