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Biomedical subjects

D Senitz

Publications and source records attributed to D Senitz.

At least 19 recordsLinked to original sources

Dendritic excrescences seem to characterize hippocampal CA3 pyramidal neurons in humans.

Excrescences are unique dendritic postsynaptic structures of the hippocampal formation. Only CA3 pyramidal neurones and hilar mossy cells possess these complex dendritic structures. Dendritic excrescences have so far only been investigated in rabbit, rat and rhesus monkey. Applying a Golgi impregnation method optimized for human brain tissue, we describe the detailed morphology of excrescences of CA3 pyramidal neurons of man. Human thorny excrescences possess a thin and single spine neck and multiple spine heads (4 on average, sometimes more than 10). Human cluster excrescences sit upon the dendrite with a broad stem, and exhibit a "papilloma-like" surface. Some human CA3 pyramidal neurons seem to possess markedly longer spine necks and larger spine heads compared to human neocortical pyramid cells; they were named long-neck spines. Thorny excrescences, cluster excrescences and the newly described long-neck spines can also be found on the dendritic main stem of human CA3 pyramidal neurons.CA2 pyramidal neurons neither possess these long neck spines nor thorny or cluster excrescences. Thus, the unique excrescences of CA3 pyramidal neurones seem to be another criterion for a demarcation between the CA3- and CA2 region of the human hippocampus.

Adult↗

Granule cells of the dentate gyrus with basal and recurrent dendrites in schizophrenic patients and controls. A comparative Golgi study.

We report on structural variability of granule cells in the human dentate gyrus. Granule cells with basal and recurrent dendrites are a normal finding in the human brain. We detect 28.3% granule cells with basal dendrites in non-psychiatrically ill humans compared to rats (2%) and primates (10%). This can be seen as an indication for the higher phylogeny of the human brain. In addition we find a significantly higher incidence of granule cells with basal dendrites (45.7%) in brains of schizophrenic patients. Whereas drug influences during lifetime cannot fully be excluded, we tend to interpret this finding as a plastic reaction to prenatal developmental malformations of the impinging rostral entorhinal region.

Adult↗

Developmental malformations in cerebral structures in "endogenous psychoses".

The last decades have revealed several structural deviances in patients with so called "endogenous psychoses". Reasonably well established are the enlargement of the lateral ventricles and subtle structural deficits in temporobasal and orbital frontal structures (hypofrontality) in a majority of schizophrenic patients. It is the aim of this investigation to examine the cytoarchitecture of these important central structures, namely the entorhinal region and the orbitofrontal cortex (Brodmann area 11) which have been under meticulous investigation in our laboratories over decades (for review: Beckmann, 2000).

Animals↗

Increased volume of the nucleus accumbens in schizophrenia.

The nucleus accumbens, an integral and important part of limbic and prefrontal cortico-striato-pallidal-thalamic circuits, is involved in several cognitive, emotional and psychomotor functions altered in schizophrenia. In animal models, developmental disturbances within the entorhinal cortex and the hippocampus induce a dysregulation of inputs to the nucleus accumbens resulting in behavioral abnormalities which point to psychotic psychopathology. Nonetheless, due to the complex neuroanatomy of the human ventral striatum hardly any morphometric data on the nucleus accumbens are available. A postmortem stereological investigation of the nucleus accumbens was performed in complete brains of 9 male schizophrenics and 9 male controls between the ages of 46 and 64. Complete serial coronal slices of both hemispheres were stained with a modified Nissl-technique. Tissue shrinkage after staining and embedding was corrected for both individual and regional shrinkage. Based on recent precise delimitations of the human ventral striatum, in vivo hemisphere-adjusted volumes of the nucleus accumbens (volume densities) and absolute accumbal volumes were calculated applying the Cavalieri-estimator. In schizophrenics, mean hemisphere-adjusted volumes of the nucleus accumbens were significantly increased on both sides (right accumbens: p = 0,005**; left accumbens: p = 0,016*). Hemispherical volumes and volumes of the nucleus accumbens were significantly correlated in both groups (p = 0,02*). Most likely, this increase in volume of the ventral striatum reflects a decrease in naturally occuring cell death following prenatal cortical neurodevelopmental disturbances.

Cerebral Cortex↗

The dendritic architecture of prefrontal pyramidal neurons in schizophrenic patients.

Despite a considerable number of investigations revealing the prefrontal cortex (PFC) to be a major site of pathological changes in schizophrenia, the neuronal basis of these alterations is still unknown. We used a 3-D image analysis technique to investigate the dendritic arborization of Golgi-impregnated prefrontal pyramidal neurons in schizophrenic patients and controls. While the apical dendrites were found to be unchanged in schizophrenics, the basilar dendritic systems were markedly reduced in the patient group. A segment analysis showed that the observed alterations were mainly confined to distal dendritic segments. The dendritic changes are likely to be associated with specific dysfunctions of prefrontal circuitry and point to the pathogenetical relevance of pre- and perinatal disturbances of PFC maturation in schizophrenic patients.

Adult↗

Age-dependent memory loss, synaptic pathology and altered brain plasticity in the Drosophila mutant cardinal accumulating 3-hydroxykynurenine.

A search for Drosophila mutants with phenotypes similar to human diseases might help to unravel evolutionary conserved genes implicated in polygenic human disorders. Among these are neurodegenerative diseases, characterized by a late onset disturbance of memory, synaptic and glial pathology, structural brain impairments and altered content of the intermediates of the kynurenine pathway, the modulators of glutamate excito- and oxidative toxicity. This pathway is conserved in insects, in rodents, and in humans. We tested the Drosophila mutants cardinal (3-hydroxykynurenine excess) and cinnabar (kynurenic acid excess) for age-dependent changes in memory, synaptic pathology, structural brain plasticity and glial immunoreactivity. The mutant cardinal demonstrated a decline in learning and memory from the 12th to the 29th day of life in a paradigm of conditioned courtship suppression. Memory decline was accompanied by a sharp decrease in immunoreactivity to the synaptic cysteine string protein, and alterations in volumetric parameters of the mushroom bodies, the brain structures implicated in memory.

Age Factors↗

Inhibitory cartridge synapses in the anterior cingulate cortex of schizophrenics.

Axon cartridges are the specific terminal structures of GABAergic inhibitory chandelier interneurons. Cartridges form axo-axonal synapses with local projection neurons, thus modulating the neuronal output of diverse brain areas. In order to examine the distribution of cartridges, the anterior cingulate cortices from the brains of schizophrenic patients and control persons were examined with an antibody against parvalbumin. Axon cartridges were mainly located in layers V and VI. In our study, schizophrenic patients showed a significantly higher density of axon cartridges than controls. These findings add new evidence for disturbances of the circuitry of the anterior cingulate cortex in schizophrenia implicating that there may be an elevated inhibitory influence on the cortical output of this brain region.

Adult↗

Disturbances of corticogenesis in schizophrenia: morphological findings provide new evidence for the maldevelopmental hypothesis.

A comprehensive neuropathology of schizophrenic psychoses has not yet been established. According to the findings of clinical investigations, neurohistological studies mainly focused on limbic structures, the prefrontal cortex and the anterior cingulate cortex. The results of morphometric and stereological studies based on the classical neuropathological techniques are controversial and point to the necessity for a differentiated characterization of the morphological features of neurons. Therefore, methods of neurobiological fundamental research are employed for the detailed demonstration of the different neuron types that constitute cortical circuits. Using these techniques, the schizophrenic cortex is shown to contain a variety of characteristic alterations which are discussed in the light of hypotheses favoring a maldevelopmental pathogenesis of schizophrenic psychoses which can be looked upon as neuronal system disorders.

Cerebral Cortex↗

Loss of human hippocampal adenosine A1 receptors in dementia: evidence for lack of specificity.

The density of hippocampal adenosine A1 receptors was measured in autopsy samples of six patients with dementia with either Alzheimer (three) or sclerosis type pathology (three) in hippocampus and six control patients. Kinetic parameters (Bmax and KD) were determined by means of quantitative autoradiography using [3H]8-cyclopentyl-1 ,3-dipropylxanthine as a radioligand. A significant 50% reduction of CA1 adenosine A1 receptors was observed in patients with dementia independent of the specific pathology. These results suggest that loss of hippocampal adenosine A1 receptors in dementia is not specific for Alzheimer type pathology.

Aged↗

A novel technique for the isolation of Lewy bodies in brain.

Previously, immunohistochemical methods were primarily used to detect and provide indirect evidence on the composition of Lewy bodies, the pathological hallmark of Parkinson's disease. This was chiefly because there are very few procedures that describe the isolation of these structures. We report here a relatively simple method that we have developed for the exclusive isolation of Lewy bodies from brain tissue. The isolation of the Lewy bodies and subsequent evaluation of their components may furnish an insight into their role in the neurodegenerative mechanism(s) operating in the spectrum of Lewy body disorders.

Aged↗

Altered distribution of parvalbumin-immunoreactive local circuit neurons in the anterior cingulate cortex of schizophrenic patients.

Several lines of evidence support an involvement of the anterior cingulate cortex in the pathophysiology of schizophrenia. Immunocytochemical techniques using antibodies against calcium-binding proteins permit a selective demonstration of certain subgroups of cortical GABAergic interneurons. The anterior cingulate cortex from the brains of schizophrenic patients and control subjects was studied with an antibody against parvalbumin. The immunoreactive structures were assessed qualitatively and quantitatively. Parvalbumin immunoreactivity was detected in a subpopulation of GABAergic local circuit neurons, in axonal structures (including axon cartridges) and in diffuse, band-like neuropil material. Schizophrenic anterior cingulate cortex was found to contain the same interneuron types as controls, but displayed a significant increase of parvalbumin-immunoreactive neuronal soma profiles in layers Va and Vb, whereas the total neuronal density determined in Nissl preparations showed no difference in the two groups. A higher density of parvalbumin-positive local circuit neurons may indicate an increased inhibition of projection neurons, thus altering the neuronal output pattern of the anterior cingulate cortex in schizophrenia.

Adult↗

Cortical layer I changes in schizophrenia: a marker for impaired brain development?

The prefrontal cortices of healthy control subjects and schizophrenic patients were examined with an antibody mixture against non-phosphorylated neurofilaments (SMI 311). SMI 311 immunoreactivity was observed in numerous pyramidal neurons of layers II to VI and in Cajal-Retzius cells (CRC) of layer I. On the basis of their Golgi-like immunostaining, CRC could be classified into three morphologically heterogeneous groups, which showed different distributions in the two proband groups. The overall density of CRC in layer I did not differ significantly between controls and schizophrenics. However, CRC were more numerous in the lower third of layer I in schizophrenics and in the upper and middle third of layer I in controls. CRC play a key role in neuronal migration, thus, our results support the neurodevelopmental hypotheses of schizophrenic pathophysiology.

Adult↗

Parvalbumin in the human anterior cingulate cortex: morphological heterogeneity of inhibitory interneurons.

The calcium-binding protein parvalbumin (PV) is a marker for a certain subset of GABAergic cortical interneurons. In the present study, indirect immunocytochemistry with an antibody against PV was performed on serial sections of human anterior cingulate cortex (Brodmann's area 24), an important relay centre of the limbic system. PV-positive structures are distributed in a layer- and cell type-specific manner. Based on morphological features and laminar distribution pattern, PV-immunoreactive interneurons are subdivided into eight different classes. PV immunoreactivity within the neuropil comprises dendritic and axonal processes. Area 24 contains two densely immunolabelled neuropil bands in layers III and Vb. Axon cartridges are preferably located in layers V and VI. The results provide a "PV immunoarchitecture' as a basis for further studies of PV immunoreactivity under pathological conditions. PV is assumed to play a role in maintaining calcium homeostasis in nerve cells, and to modulate neuronal excitability and resistance to biochemical damage. On the other hand, PV immunoreactivity has recently been shown to undergo characteristic changes during different stages of brain maturation. Therefore, examination of PV-positive structures will provide new insights into cortical circuitry in neurodegenerative as well as neurodevelopmental disorders.

Adult↗

Surface complexity of human neocortical astrocytic cells: changes with development, aging, and dementia.

Astrocytes from area 11 of the human neocortex were Golgi-impregnated. The material was taken from four human subjects, (1) a neonate without obvious CNS damage, (2) a middle-aged adult serving as control, (3) an aged individual without apparent mental disturbances, and (4) an aged patient with dementia. Camera-lucida drawings of 7 to 26 astrocytic cells from each donor were digitized into a personal computer, and analyzed for their fractal dimension D which is an objective and quantitative measure of the complexity of the cell's borders. Both radial and multipolar astrocytes from neonatal cortex showed a comparatively low fractal dimension (D approximately 1.39), that is, low surface complexity. Adult ("control") astrocytes were characterized by a high fractal dimension (D = 1.57), corresponding to their large surface complexity. Astrocytes from the aged subject showed a somewhat smaller fractal dimension (D = 1.51) and, thus, surface complexity; this difference was however not highly significant. In contrast, astrocytes from the subject with dementia showed a significant reduction in surface complexity (D = 1.47). Parallel changes were observed in the brain volume compartment occupied by the process of individual astrocytes. These data suggest that formation and maintenance of astrocytic processes and/or side branches correlate positively with the degree of information processing within their neuronal environment.

Adult↗

Presentation of human neocortical neurons stained with the carbocyanine dye dil compared to the Golgi silver impregnation technique.

The carbocyanine dye Dil (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) not only serves as an excellent neuronal tracer, but also produces staining of neurons similar to the results of the Golgi technique. In one aspect staining with Dil seems superior to the Golgi technique: the axons are well stained and show morphological details of their structure. The dendrites and the spines can also be studied easily so that this technique seems to be a promising alternative of the Golgi technique. The fading of the fluorescence could probably be overcome by photoconversion of the stained neurons.

Brain↗

How to run a brain bank. A report from the Austro-German brain bank.

The sophisticated analysis of and growing information on the human brain requires that acquisition, dissection, storage and distribution of rare material are managed in a professional way. In this publication we present the concept and practice of our brain bank. Both brain tissue and information are handled by standardized procedures and flow in parallel from pathology to neuropathology and neurochemistry. Data concerning brain material are updated with clinical information gained by standardized procedures.

Austria↗

A comparative fractal analysis of various mammalian astroglial cell types.

Camera-lucida drawings of Golgi-impregnated astroglial cells and their processes are described by the fractal dimension of their borders, which is an objective, quantitative measure of morphological complexity. Protoplasmic astrocytes from human neocortex have fractal dimensions (D) that are larger than those of fibrous astrocytes from the cat optic nerve. Marginal astrocytes from monkey cerebropontile angle have two kinds of processes: (1) short, thick processes with endfeet abutting the pial surface, with relatively high D's, and (2) very long, thin processes extending into the neuronal tissue, with very low D's. These data indicate that short astrocytic processes may have a complex surface (and have a high D), whereas long processes are rather smooth (and have a low D). A comparison between transmission electron microscopy morphometry and measures of D at the light microscopic level, performed on different parts of rabbit retinal Müller glial cells, suggests that D is strongly correlated to the surface-to-volume ratio which, in part, determines the length constant of a cable for core-conductance of currents. We provide data supporting the hypothesis that astroglial cell geometry is adjusted to allow for sufficient spatial buffering K+ currents, even through very long processes.

Animals↗