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K Zilles

Publications and source records attributed to K Zilles.

At least 217 records · Page 12Linked to original sources

Muscarinic cholinoceptive neurons in the frontal cortex in Alzheimer's disease.

The cellular distribution of muscarinic acetylcholine receptor protein in the frontal cortex of Alzheimer (AD) patients, age-matched and middle-aged controls was assessed quantitatively by means of immunohistochemistry using the monoclonal antibody M35. As shown previously in biopsy cortices, mainly layer II/III and V pyramidal neurons were immunolabeled. Neither distribution nor numbers of labeled cells displayed significant differences between the groups investigated. This is in accordance with the results of ligand binding studies that mostly failed to reveal different binding characteristics in AD compared to controls. Muscarinic and nicotinic receptor proteins have been shown to be colocalized in many cholinoceptive pyramidal neurons. Since nicotinic receptors--in contrast to muscarinic receptor proteins--are severely reduced in AD, this indicates a selective impairment of nicotinic receptor expression and not a significant death of cholinoceptive neurons per se.

Aged↗

Cellular distribution and expression of cortical acetylcholine receptors in aging and Alzheimer's disease.

Ligand binding studies show marked reductions of nicotinic, but not of muscarinic binding sites in Alzheimer's disease. Using monoclonal antibodies we studied immunohistochemically the expression of the respective receptor proteins in the frontal cortex of middle-aged (55 +/- 5 yr) controls, age-matched controls (73 +/- 6 yr), and patients with Alzheimer's disease (74 +/- 5 yr). Density of nicotinic cholinoceptive neurons was 8000/mm3 for middle-aged controls and 4000/mm3 for age-matched controls, but only 900/mm3 in Alzheimer's brains (p less than 0.0001). Densities of muscarinic cholinoceptive and of Nissl-stained neurons were not significantly different between the groups, pointing to a selective decrease of nicotinic receptor protein expression in cortical neurons with aging and in Alzheimer's disease.

Aging↗

Encephalization in hummingbirds (Trochilidae).

The brain mass in 23 hummingbird species was compared to that in galliform birds taking body mass into consideration. Hummingbird brain masses were determined by endocranial volumes, and their body masses were calculated from skeletal measurements. Galliform data were taken from a recent publication. Hummingbirds have brains that are approximately 2.5 times larger than those of galliform birds. Such encephalization may be due to (1) an enlargement of the telencephalon, or (2) an enlargement of functionally well-defined extratelencephalic brain parts. Based on the extremely specialized feeding behavior of the nectarivorous hummingbirds and the neurological demands associated with sucking nectar during hovering, the second hypothesis is better supported, but further studies are needed.

Animals↗

Quantitative development of brain and brain structures in birds (galliformes and passeriformes) compared to that in mammals (insectivores and primates).

The brain weight and brain structure volumes of galliform and passeriform birds were calculated and related to body weight. The total brains and 14 brain regions were investigated in order to calculate factors by which these structures in passeriforms exceed those in galliforms in size. The larger passeriform brains have larger telencephala, especially ventral hyperstriata and neostriata. The enlargement of total brain and telencephalon resembles that in primates, compared to insectivores, within mammals. The enlargement of the ventral hyperstriata + neostriata in passeriforms is fundamentally similar to that of the isocortex in mammals: it reflects an expansion of multimodal integrational capacities, as the ventral hyperstriatum and neostriatum are occupied exclusively or primarily by multimodal integrational areas as is the isocortex.

Animals↗

Neurotransmitter receptors and cortical architecture.

Quantitative receptor autoradiography is a widely used technique for the demonstration of transmitter receptor distributions in anatomically defined brain regions. The present paper reviews some aspects of the relation between receptor distributions and cortical architecture in adult and early postnatal mammalian brains. 1. Changes in the distribution (mean density, laminar pattern) of transmitter receptors occur often at the borders of cyto- and myeloarchitectonically defined cortical areas. This corroborates the functional meaning of the classical cyto- and myeloarchitectonical parcellations. 2. Some, but not all receptor subtypes of one transmitter system and receptors of different transmitter systems show similar laminar patterns (codistribution) and colocalizations at the single cell level. Both aspects are important for a functional interpretation of cortical units (areas, layers, etc.) and neuronal cell types, because the interaction between numerous transmitters and their receptors is the neurochemical substrate of neurotransmission in vivo. Codistributions and colocalizations are prerequisites for such interactions. 3. Overshooting alpha 1-adrenoceptor production, heterochronous development of this receptor in the different layers of a cortical area, and different time tables of cortical histogenesis, increase in transmitter concentrations and local receptor maturation demonstrate that the processes regulating the development of transmitter receptors during postnatal ontogeny cannot be directly deduced from histogenetic events or transmitter maturation in the cortex. 4. Receptors of one transmitter (e.g., alpha 1-adrenoceptors) can be specifically associated with a neuronal projection system (e.g., hippocampal mossy fibers), which is using a different transmitter (e.g., L-glutamate). This points to complex interactions between different transmitter systems in an anatomically defined structure. Functional and architectonical cortical units (e.g., "barrels") show specific receptor distributions, and hitherto unknown modular structures (e.g., periodical concentrations of alpha 1-adrenoceptors in layer V of the rat posteromedial barrel subfield) can be visualized by quantitative receptor autoradiography combined with image analysis.

Aging↗

The significance of complement in proliferative vitreoretinopathy.

Complement is the principal effector arm of antibody-mediated allergic response and plays a central role in the pathogenesis of many immunologic disorders. The possible pathophysiologic importance of complement was examined in the development of proliferative vitreoretinopathy (PVR). Vitreous aspirates from patients with idiopathic PVR (n = 21) and traumatic PVR (n = 15) were examined for total vitreal protein (TVP) and complement components C3, C3d, C4, and C1q-fixed immunoglobulins using enzyme-linked immunosorbent assay (ELISA), sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and western blotting. The TVP, C3 components, and factor C4 were elevated significantly in diseased vitreous. The C3-TVP and C4-TVP ratios showed no difference between traumatic and idiopathic PVR. A C4 index to estimate the rate of intraocular C4 synthesis had a mean value of 3.2 (n = 15). The increased relative amount of C3d reflected complement activation in diseased vitreous. The negative values in normal human serum and plasma and in patient plasma samples (n = 15) indicated a local reaction in the eye. The authors found C1q-fixed immunoglobulin G; this may be the cause of complement activation by the classic pathway. These findings support the opinion that the cause of PVR may be based partly on an autoimmune reaction against ocular structures.

Autoimmune Diseases↗

Immunocytochemical visualization of muscarinic cholinoceptors in the human cerebral cortex.

The monoclonal antibody M 35 was used to study the cellular and subcellular distribution of muscarinic acetylcholine receptors in the human cerebral cortex. M35, raised against purified muscarinic receptor protein, exerts muscarinic agonist-like effects at cholinergic synapses. Applied to human cortical tissue immediately fixed upon neurosurgical removal, light microscopically M 35 revealed immunoreactive perikarya predominantly of the pyramidal cell type in layers II/III and V, their labeled apical dendrites extending into the superficial layers. Furthermore, immunoprecipitate decorated distinct regions of the perikaryal cytoplasm, numerous dendritic profiles and synapses of both symmetric and asymmetric appearance. In the perikarya immunoprecipitate was associated with ribosomes, the endoplasmic reticulum and the Golgi apparatus. In dendrites the microtubular system, in synaptic complexes the postsynaptic membranes were decorated. The results suggest that novel informations about the cell type specific and subcellular distribution of human muscarinic cholinoceptors can be obtained by M 35 immunocytochemistry.

Adult↗

Remote astrocytic response as demonstrated by glial fibrillary acidic protein immunohistochemistry in the visual cortex of dorsal lateral geniculate nucleus lesioned rats.

The reaction of astroglia was investigated after unilateral destruction of the dorsal lateral geniculate nucleus in the primary visual cortex of adult albino rats. The destruction of the dorsal lateral geniculate nucleus was performed by stereotaxic injections of ibotenic acid, and the location was verified in Nissl stained sections in each animal. Electron microscopic observations demonstrated the presence of degenerating axon terminals surrounded by hypertrophic astroglial processes mainly in layers III and IV of the ipsilateral primary visual cortex. The ipsilateral (impaired) and contralateral (control) sides of the primary visual cortex showed light microscopically a clearly differing appearance and distribution of glial fibrillary acidic protein (GFAP) immunoreactivity 7 to 11 days after the unilateral injection of ibotenic acid into the dorsal lateral geniculate nucleus. Whereas the control side of the primary visual cortex showed GFAP staining only in the subpial zone of layer I and close to the white matter, all layers of the impaired cortex showed an intense GFAP immunoreactivity. The increase in immunoreactivity was confined to the primary visual cortex. The extent of and increase in immunoreactivity was corroborated by image analysis. These findings were interpreted as a localized hypertrophy of astroglia caused by the anterograde degeneration of geniculocortical terminals. This hypertrophy is accompanied by an increase in GFAP, which may represent the stabilization of the cytoskeleton of newly formed glial processes involved in the rearrangement of the impaired neuropil.

Afferent Pathways↗

Local cerebral glucose utilization in the neocortical areas of the rat brain.

The neocortex of the rat brain can be subdivided into regions of different local cerebral glucose utilization (LCGU). However, only a few neocortical areas can be delineated by differences in mean LCGUs between neighbouring areas. These area borders correspond exactly with cytoarchitectonically defined borders found in adjacent Nissl-stained preparations. On the other hand, nearly all of the architectonically defined area borders are also recognizable in the LCGU pictures, if differences in laminar distribution patterns of LCGU are taken into account. Furthermore, interareal differences in mean LCGU mainly reflect changes in layer IV, whereas layers II-III and V-VI show nearly identical LCGU values in all neocortical areas of the rat brain. The primary sensory areas exhibit the highest LCGU in layer IV, while the primary motor cortex shows a high LCGU in layer V. As the cytoarchitectonically defined pattern of the cortex is generally corroborated by the regional and laminar LCGU distribution, anatomical, metabolic and functional aspects of cortical architecture are associated.

Animals↗

Quantitative analysis of the retrograde reaction of motoneurons with an image analyser.

The neuronal profiles of cell bodies in the facial nerve nucleus of adult rats were measured after partial peripheral nerve transsection. An image analyser was used for automatic recognition and morphometry. Based on classification of the neuronal profiles described in a previous paper, a morphometrical study was performed in order to analyse structural aspects of the retrograde reaction in quantitative terms. Beside the quantification of classical features of retrograde reaction (chromatolysis; nuclear eccentricity; increased basophilia; perikaryal, nuclear and nucleolar swelling), several reactive changes so far not recognized (karyoplasmic basophilia and granulation) were detected. These changes were interpreted as morphological correlates of regeneration in retrogradely reacting cells.

Animals↗

Vasoactive intestinal polypeptide (VIP) containing cells in the developing rat occipital hemisphere.

Numerous cells were observed to show intense vasoactive intestinal polypeptide (VIP) immunoreactivity from birth to postnatal day 8 in the subventricular zone of the rat occipital hemisphere. This cell population was markedly reduced by postnatal day 8, but isolated clusters of VIP cells persisted into adulthood. In addition, long, L-shaped VIP fibers were seen in the hemispheric wall up to postnatal day 16, but not in the adult. Parallel to the reduction in number of the subventricular VIP cells an increasing number of VIP cells appeared in the neo- and allocortex, developing by postnatal day 12 all the features of the mature cortical bipolar fusiform neurons. As possible alternatives, the migration of subventricular VIP cells into the cortex, the transient character of the subventricular VIP population or the expression of VIP by radial glia are discussed.

Aging↗

Ultrastructure of PkC(II/III)-immunopositive structures in rat primary visual cortex.

In the primary visual cortex of adult rats the cellular and subcellular distribution of protein kinase C isozymes II and III (PkCII/III) was examined by immunohistochemical methods with a monoclonal antibody against PkCII/III. Strong PkC(II/III)-immunoreactivity was found in neurons and astrocytes. Immunopositive neurons exhibited morphological features characteristic for both pyramidal and non-pyramidal cells. They were distributed in layers II through VI but were concentrated in layers II/III. At the electron microscopic level immunoprecipitate was found predominantly in distinct regions of the somata, except the nuclei, and only a few labeled dendrites and axons were seen. Two different patterns of cytoplasmic immunoreactivity could be distinguished. In most neurons, PkC(II/III)-staining was confined to cytoplasmic spots associated with the Golgi complex, while a few neurons exhibited additional labeling in the vicinity of the cell membrane. Moreover, PkC(II/III)-immunoreactivity was present in numerous astroglial processes and in the perikaryal cytoplasm of a subpopulation of astrocytes. The present data provide morphological indications for specific functions of PkC isozymes II and III in neurons as well as in astrocytes.

Animals↗

A new method for quenching correction leads to revisions of data in receptor autoradiography.

Differential quenching of beta-emission affects strongly the analysis of receptor distribution patterns in quantitative receptor autoradiography with tritiated ligands. Different methods for the quenching correction have been described in the past, but some of these are of limited value, if a detailed anatomical parcellation is necessary. Other methods correct exclusively local variations in lipid concentration, which is an important, but only one of several factors causing quenching. A new method for the measurement of quenching (or autoradiographic efficiency) is presented, which permits an anatomically detailed and direct determination of the total quenching without lipid extraction procedures. This method is based on the measurement of autoradiographic efficiency in cryostat sections homogeneously labeled with tritiated formaldehyde by an underlying gelatine section containing this labeled compound. Regional and layer specific measurements of autoradiographic efficiency in cortical and subcortical regions of the human and rat brain are reported. A significant correlation was found between the density of myelin and autoradiographic efficiency but other factors were also shown to influence differential quenching. The use of the here presented correction procedure leads to revisions of the laminar distribution patterns reported for different receptors in human and rat cortical areas. Our results show, that a complete quenching correction is necessary for the mapping of receptor distributions with tritiated ligands.

Animals↗

Total surface of temporoparietal intrasylvian cortex: diverging left-right asymmetries.

Measurements of the total convoluted surface area of cortex buried in the temporoparietal transition of the Sylvian fissure were performed using "three-dimensional" magnetic resonance morphometry in 10 randomly selected human cadaver brains. The measurements comprised the planum temporale, which covers the superior temporal gyrus posterior to Heschl's first transverse gyrus, and the caudally adjacent walls of the descending and ascending rami of the Sylvian fissure. Also, the total convoluted surface of the planum temporale was compared with its superficially exposed surface as determined by photographical planimetry after brain section, so that the index of cortical folding of the planum temporale could be estimated. The following results were obtained: Cortical folding of the planum temporale did not differ significantly between left and right hemispheres (p greater than .6). The total and the superficially exposed surface of the planum temporale showed significant leftward asymmetry (p less than or equal to .0078). In contrast, the total surface of cortex buried in the caudal segments of the Sylvian fissure posterior to the planum exhibited significant rightward asymmetry (p less than or equal to .016). The combined cortical surface area buried in the whole posterior Sylvian fissure caudal to the first transverse gyrus did not show significant left-right asymmetry (p greater than 0.3). The data suggest divergent lateral asymmetries in the posterior intrasylvian region with excesses of superior temporal cortex in left hemispheres and of supramarginal cortex in right hemispheres.

Aged↗

Image analysis of Nissl-stained neuronal perikarya in the primary visual cortex of the rat: automatic detection and segmentation of neuronal profiles with nuclei and nucleoli.

An image analysing procedure for the morphometric characterization of cortical neurons in Nissl-stained brain sections is described. It consists of the automatic detection of cellular profiles and their compartments: cytoplasm, nucleus and nucleolus. The algorithm was designed to cope with the large morphological spectrum of cortical perikarya (e.g. geometrical properties of perikarya, staining intensities of cell compartments and nucleo-plasmic area-ratio) including pyramidal (Golgi-category I) and non-pyramidal (Golgi-category II) neurons. Clusters of cells were separated and non-neuronal structures (e.g. glia, endothelial cells) as well as tangential, non-nucleolated sections through neuronal perikarya recognized and excluded from further analysis without requiring interactive procedures. The performance of the profile recognition procedure was evaluated using 426 nucleolated and non-nucleolated profiles of different types of neurons in the primary visual cortex of the rat. Nucleolated profiles were recognized as such with a 91% accuracy, non-nucleolated profiles were rejected correctly in 90% of cases. After automatic segmentation and selection of nucleolated neuronal profiles from the microscopic field, a large set of quantitative morphological features including geometrical, densitometrical and textural parameters can be measured using high power light microscopy. This permits quantitative morphometric characterization of different neuronal types. This procedure is the first part of a system for the automatic classification of Nissl-stained cortical neurons.

Algorithms↗

A quantitative approach to cytoarchitectonics: analysis of structural inhomogeneities in nervous tissue using an image analyser.

Cytoarchitectonic investigations are based on the analysis of structural inhomogeneities in the neuronal composition of nervous tissue. Boundaries of brain regions are established at locations where local structural properties, such as density, shape, orientation or arrangement of the nerve cells, change. A quantitative approach requires a complete scanning of histological sections and the measurement of at least one of these properties using an automatic device. In contrast to recently developed stereological methods which result in unbiased estimates of parameters and which are based on efficient sampling procedures, measurements with automatic devices are biased due to section thickness and problems in the segmentation of nerve cell bodies. Automatic measurements are necessary, however, if a complete scanning of histological sections is required in order to localize areal or laminar boundaries. In this approach, the grey level index (GLI) is measured with a TV-based image analysing system from routine histological sections. Using Nissl-staining, this parameter is a biased estimate of the local volume density of Nissl-positive structures (cell bodies). The histological section is digitized into a GLI image by a scanning procedure. The GLI image is processed by image enhancement procedures in order to visualize the laminar pattern. Areal boundaries are localized at positions where this laminar pattern changes. GLI statistics of single brain regions can easily be evaluated by delineating these regions with a cursor in the GLI images of the sections. Information from a series of sections is compiled by specific application programs.

Animals↗