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K Zilles

Publications and source records attributed to K Zilles.

At least 19 recordsLinked to original sources
PubMed1992

Muscarinic desensitization after septal lesions in rat hippocampus: evidence for the involvement of G-proteins.

Three days after bilateral septal lesions, regional and laminar densities of the muscarinic acetylcholine receptors of the dorsal rat hippocampus were studied. The concentration of [3H]N-methylscopolamine binding sites and muscarinic M1 and M2 receptor subtypes, as well as the affinity of muscarinic receptors and their sensitivity to modulation by 5-guanylylimidodiphosphate were analysed by quantitative receptor autoradiography. The measurement of these parameters was performed with a computerized image-processing system allowing a spatial resolution down to the level of single hippocampal layers. No postlesional changes of the density of M1 receptors were detected. M2 receptors showed a remarkable decrease in concentration (less than 21%) in some hippocampal layers after septal lesions. In competition experiments the affinity of muscarinic receptors for the cholinergic agonist carbamylcholine chloride decreased significantly in all hippocampal subregions and layers of the lesioned animals. In contrast to controls, the sensitivity of muscarinic receptors of the lesioned animals could not be modulated by 5-guanylylimidodiphosphate. These findings demonstrate a desensitization of muscarinic receptors in the rat hippocampus three days after septal lesions, which is caused by changes of the coupling of guanine nucleotide-binding proteins to muscarinic receptors. Therefore, the lesion-induced alteration of the muscarinic receptor-effector complex is a major aspect of the hippocampal plasticity after cholinergic denervation.

Animals↗
PubMed1992

Neuronal plasticity as an adaptive property of the central nervous system.

This short review presents examples of plasticity in the brains of vertebrates including man. The basic ability of the nervous system to make functionally relevant adaptations to functional challenges of various kinds during development and adulthood is called plasticity. Enucleation of the eyes or lesioning of the lateral geniculate body during development lead to the generation of a new architectonic area within the nonhuman primate and human primary visual cortex. The enucleation of one eye in rats at various postnatal stages causes profound plastic changes in the callosal system of the visual cortex. The central representation of the periphery in the adult cerebral cortex (somatotopy) can also be altered by adaptive processes. Naturally occurring nerve cell death during pre- and early postnatal development can be manipulated by impairing normal development of neuro-transmission. These findings argue for an important role of transmitter receptors in brain plasticity. The number of receptors shows, for most brain regions and receptor types, an overshoot of growth during ontogeny. After lesions have damaged the adult geniculo-cortical and septo-hippocampal systems, receptors can exhibit plastic changes such as upregulation of the number of binding sites (visual cortex) and modifications in the coupling of receptors, transducer proteins (G-proteins) and second messengers (hippocampus).

Aging↗
PubMed1992

Plasticity in the rat hippocampal formation following ibotenic acid lesion of the septal region: a quantitative [14C]deoxyglucose and acetylcholinesterase study.

The local cerebral glucose utilization was measured in the hippocampal formation 3, 21, and 90 days after bilateral lesions of the medial septal nucleus and the nucleus of the diagonal band of Broca by multiple ibotenic acid injections. The CMRglc was determined in hippocampal areas and layers and various limbic and visual regions by quantitative [14C]2-deoxyglucose autoradiography using a computerized image-processing system. Three days after lesion, CMRglc was significantly decreased in 26 of the 38 structures examined. The most pronounced reductions were found in CA2 and CA3, the subiculum, and the parasubiculum. The CMRglc values of the 21- and 90-day postlesion groups did not differ significantly from control data when univariate statistics were used. However, by means of a factor analysis and subsequently a discriminant analysis as a multivariate test for group differences, significant lesion-induced CMRglc changes could be detected between the control group, the 3-day group, and the 90-day group. The 21-day group did not differ significantly from the controls. The data indicate that 90 days after lesion of the medial septum/diagonal band complex (MSDB), a considerable recovery of the mean CMRglc was found in the hippocampal region, although a normal level was not reached. In a parallel series, processing of sections for acetylcholinesterase (AChE) histochemistry revealed a severe destruction of AChE-positive fibers in the hippocampus at 3 days after lesion and a conspicuous recovery in the amount of stainable fibers and their staining intensity at 21 days postlesion. In the 90-day group, the AChE fibers recovered even further but did not reach the values of unlesioned sham-operated controls. The present study indicates that sprouting of surviving cholinergic afferents might be an important morphological substrate for CMRglc recovery in the hippocampus after MSDB lesion.

Acetylcholinesterase↗
PubMed1991

Glycine receptor immunoreactivity in rat and human cerebral cortex.

The distribution of the inhibitory glycine receptor was studied in rat and human cerebral cortex using a monoclonal antibody (MAb 4a) directed against the ligand-binding subunit. Significant amounts of glycine receptor antigen were found in forebrain structures such as caudatum and neocortex, although cortical levels were significantly below those seen in spinal cord. Immunohistochemically, glycine receptors were preferentially localized to the apical dendrites of pyramidal neurons in layers III and V. Ultrastructurally, these sites corresponded to synaptic neuronal contacts. Immunoreactivity was found in neuronal perikarya, dendrites and postsynaptic membranes which may correspond to sites of intracellular synthesis, transport and membrane incorporation of the glycine receptor. These immunological data corroborate previous pharmacological studies suggesting the existence of glycinergic transmission in mammalian cerebral cortex.

Aged↗
PubMed1991

Developmental gradients of vasoactive intestinal polypeptide (VIP)-containing neurons in the rat visual cortex detected by image analysis.

The postnatal development of vasoactive intestinal polypeptide-immunoreactive (VIP-IR) neurons was followed by computer-assisted image analysis in the rat visual cortex. The laminar distribution of all VIP-IR structures was measured. These structures were subdivided into cell somata, dendritic profiles and axonal boutons and measured separately. VIP-IR neurons were first seen on postnatal day 1, mostly in the upper half of the presumptive visual cortex. A localization of cell bodies similar to that in the adult is reached between days 12 and 16. VIP-IR dendrites have a protracted growth period as compared to perikarya, involving a developmental gradient from an even distribution to a concentration in the upper cortical layers. This is due to the formation of dendritic terminal arbors after the second postnatal week. Scattered VIP-IT axonal boutons appear on day 3 in the midportion of the presumptive visual cortex. Their typical laminar distribution in layers II, IV and lower VI was observed after day 12. Our results suggest that the biochemically detected sharp increase in VIP levels after the second postnatal week is due to the maturation of cell processes as a morphological basis of neuronal connectivity.

Aging↗
PubMed1991

Mapping of glial fibrillary acidic protein-immunoreactivity in the rat forebrain and mesencephalon by computerized image analysis.

Computer-assisted image analysis was used to map the regional distribution of glial fibrillary acidic protein-immunoreactive (GFAP-IR) astrocytes in the rat forebrain and mesencephalon. A complete survey of packing densities of GFAP-IR structures was performed. Computer maps revealed high values in the outer and inner layers of the cortex, some hippocampal and olfactory bulb layers, prepiriform cortex, dorsal part of the caudate-putamen, globus pallidus, lateral septum, reticular thalamic nucleus, lateral habenular nucleus, circumventricular organs, nuclei of the medial hypothalamus, substantia nigra, interpeduncular nucleus, and mamillary body. These correspond to regions of the embryonic pial and ventricular brain surfaces, which undergo developmental alterations including growth and various forms of internalization. From this we conclude that in the adult brain, astrocytes of high GFAP-IR are derivatives of surface-contact glia, whereas those located in areas having developed by the local thickening of the neural tube wall show reduced or no GFAP-IR.

Animals↗
PubMed1991

An immunochemical quantitative analysis of the protein pattern in physiologic and pathologic vitreous.

Biochemical changes in the vitreous in different vitreoretinal disorders have not yet been thoroughly studied. Using enzyme-linked immunosorbent analysis (ELISA), we established mean values and 95% confidence intervals for six proteins of physiologic human vitreous: albumin (293 +/- 18 mg/l), transferrin (73.7 +/- 6.6 mg/l), immunoglobulin G (IgG), (33.5 +/- 3 mg/l), alpha 1-antitrypsin (14.1 +/- 2.9 mg/l), alpha 1-acid glycoprotein (4 +/- 0.7 mg/l), and lactoferrin (less than 50 micrograms/l). These six proteins were also determined in vitreous aspirates from patients with idiopathic proliferative vitreoretinopathy (n = 10), traumatic proliferative vitreoretinopathy (n = 10), and proliferative diabetic retinopathy (n = 15). The pattern of protein levels varied widely within each of the disorders. An analysis of absolute protein levels showed significant differences in total protein and alpha 1-antitrypsin levels between controls and pathologic vitreous samples. We observed differences in transferrin between controls and proliferative diabetic retinopathy (PDR), and differences in alpha 1-acid glycoprotein between controls and both types of proliferative vitreoretinopathy (PVR). The single disorders themselves could not be differentiated by any of the proteins. When the relative contribution of single proteins to total vitreal protein was compared, albumin was lower in all three disorders than in controls. Transferrin was lower in traumatic PVR than in controls, in PDR, or in idiopathic PVR. Our results indicate that the three vitreoretinal disorders studied are characterized by a breakdown of blood-ocular barriers.

Albumins↗
PubMed1991

Postnatal development of forebrain regions in the autoimmune NZB-mouse. A model for degeneration in neuronal systems.

NZB-mice are known to have impaired cognitive functions. The aim of the present study is the analysis of the volume growth of different brain regions in NZB/NBOM-mice, because the functional impairment increases postnatally. The regions analysed include brain structures which are important for learning and memory functions. The comparison between NZB-mice and controls (CFW- and Balb/c-mice) shows that the hippocampal volume in NZB-mice is larger than in controls. However, ectopic neurons are found in the dentate gyrus of NZB-mice, indicating a changed connectivity in this region. The septum and the amygdala show no difference in volume in NZB-mice compared to controls. The adult volume of the entorhinal cortex of the NZB-mice is the smallest of the three strains. The development of this brain region is characterized by an overshooting growth in all strains. The caudate-putamen complex and the globus pallidus of NZB-mice undergo a reduction in volume during the postnatal period. This is not found in the controls. An overshooting growth is seen in the mamillary bodies of the three strains, and in the anterior thalamic nucleus of NZB-mice. However, only the NZB-mice show a prolonged reduction of the volume of the mamillary bodies, which is not finished during the observed time period. Both regions are important relay stations in the Papez-circuit, a neuronal system associated with learning and memory functions. The prolonged postnatal reduction in volume of the mamillary bodies and the anterior thalamic nucleus of NZB-mice may be the structural correlate of the impaired cognition and memory in this strain.

Animals↗
PubMed1991

Local cerebral glucose utilization in the brain of old, learning impaired rats.

The local cerebral glucose utilization (LCGU) was measured in 63 different cortical areas and nuclei of the telencephalon, diencephalon and rhombencephalon of young adult (3 to 4-month-old) rats and of 27-month-old Wistar rats, in which learning impairments had been proven by a water maze test. The LCGU was determined by [14C]2-deoxyglucose autoradiography. In the old rats the mean LCGU of all brain regions was significantly reduced by about 10% compared with the young control group; the mean LCGU was 74.2 mumol glucose/(100 g x min) in the young and 66.7 in the old rats. Different degrees of LCGU decrease were found in the different regions. Most of the brain regions with significantly reduced LCGU values in the aged, learning impaired rats were associated with auditory and visual functions, the dopaminergic system, and structures known to be involved in learning and memory processes. Therefore, the regional pattern of LCGU reduction found in the aged, learning impaired rats did not resemble any known pattern found after lesions of a single transmitter system or systemic administration of transmitter agonists or antagonists.

Aging↗
PubMed1991

Parallel evolution in mammalian and avian brains: comparative cytoarchitectonic and cytochemical analysis.

Comparative morphology, which is based on the selection theory of evolution, analyses the impact of function upon structure and, therefore, emphasizes the adaptive events and biological advantage during the evolution of organs. A comparison based on analogies is described here as an adequate method. The hypothesis is proposed that the evolution of the brain follows the same trends in birds as in mammals. This hypothesis is proved by (1) allometric studies of brain weight and brain structure volume in relation to body weight in mammals and birds; (2) architectonic studies using image analysis on cell and fibre stains as well as on histochemical preparations and receptor autoradiography; and (3) hodological studies with injections of [3H]leucin, HRP and WGA-HRP. The results reveal a vast amount of structural and functional similarities in avian and mammalian brain organization, especially an expansion of structures that permit multimodal integration capacity in the telencephalon. Thus, a parallel evolution occurred in these two groups of vertebrates. It is argued that this may be a general phenomenon in evolution. A cladistic approach, which is based on the concept of homologies (plesio-, apomorphies), pushes aside the existence of analogies. For this reason, cladism does not seem to be a method to answer questions of evolutionary morphology adequately.

Animals↗
PubMed1991

Distribution of glial fibrillary acidic protein and vimentin immunoreactivity during rat visual cortex development.

The postnatal maturation of astrocytes in the rat visual cortex was analysed by immunostaining the astroglial proteins vimentin and glial fibrillary acidic protein with poly- and monoclonal antibodies. Vimentin immunoreactivity was present in the visual cortex up to the third postnatal week, whereas immunolabelling first disappeared in the cortical layers and then in the white matter. In the early postnatal period, vimentin antibodies labelled radial glial fibres. After the first postnatal week staining of radial glial fibres gradually disappeared and vimentin immunoreactivity was localized in a few protoplasmic astrocytes in the grey matter and fibrous astrocytes in the white matter. The development of glial fibrillary acidic protein-positive astrocytes was not fully complete until postnatal day 50. Glial fibrillary acidic protein-positive radial glial fibres were present after birth and disappeared towards the end of the third postnatal week. Staining of astrocytes in the white matter and in cortical layers I and VI reached an adult density at postnatal days 8 and 20, respectively. A progressively later development of glial fibrillary acidic protein-positive astrocytes was observed in cortical layers II-V which was completed between postnatal days 47 and 50. In the adult rat visual cortex glial fibrillary acidic protein-positive astrocytes were especially dense in layers I and VI, moderate in layers II/III and V and nearly absent in layer IV and lower layer III. The time course of the loss of vimentin and the gradual appearance of glial fibrillary acidic protein immunoreactivity in the visual cortex is considered as an index of astrocytic maturation and the spatiotemporal sequence of this maturation pattern is discussed in terms of reciprocal neuron-astrocyte interactions during brain development.

Animals↗
PubMed1991

Regional and laminar distributions of alpha 1-adrenoceptors and their subtypes in human and rat hippocampus.

The distributions of the alpha 1-adrenoceptor and its subtypes (alpha 1A and alpha 1B) in human and rat hippocampus are analysed by quantitative receptor autoradiography. alpha 1-Adrenoceptors are labelled by [3H]prazosin. The alpha 1A subtype is visualized by [3H]prazosin after irreversible blockade of alpha 1B adrenoceptors with chloroethylclonidine or directly by [3H]5-methyl-urapidil. The alpha 1B subtype is investigated by [3H]prazosin binding in the presence of the alpha 1A antagonist 5-methyl-urapidil. Considerable differences in the regional and laminar patterns of alpha 1-adrenoceptors are found between rat and human hippocampi. The rat hippocampus is characterized by a low overall density and a rather homogeneous regional and laminar distribution. This is in contrast to the human pattern, which shows a much higher overall level of alpha 1 receptor density and a restriction of alpha 1 receptors to the CA3 region of Ammon's horn and the dentate gyrus. Moreover, alpha 1A and alpha 1B receptors of the human hippocampus are differentially distributed with the alpha 1A subtype concentrated in the hilus and lucidum layer of CA3, and the alpha 1B subtype concentrated in the molecular layer of the dentate gyrus. Additionally, the distribution of alpha 1 receptors is compared with the distribution of 5-hydroxytryptamine 1A receptors. The subtype specific pattern is correlated with the distribution of glutamatergic systems in the human (but not in the rat) hippocampus. alpha 1A Receptor localization coincides with the target area of the mossy fibre system, and alpha 1B receptors are preferentially localized in the target area of the hippocampal associational fibres and partly of the perforant pathway. This result points to possible interactions between noradrenaline- and glutamate-mediated neurotransmission differentiated by topographically segregated alpha 1-adrenoceptor subtypes.

Adrenergic alpha-Antagonists↗
PubMed1991

Quantitative autoradiography of 11 different transmitter binding sites in the basal forebrain region of the rat--evidence of heterogeneity in distribution patterns.

The distribution of 12 different binding sites for acetylcholine, L-glutamate, GABA, 5-hydroxytryptamine, dopamine and noradrenaline was measured with quantitative receptor autoradiography in four regions of the rat basal forebrain (medial septal nucleus including vertical and horizontal limbs of the diagonal band of Broca, magnocellular preoptic nucleus, substantia innominata and basal nucleus of Meynert, ventral pallidum). L-Glutamate binding sites represent the largest portion of the analysed receptors in all regions, followed by muscarinic2, 5-hydroxytryptamine1 and GABAA receptors. Muscarinic1, dopamine1, dopamine2 and 5-hydroxytryptamine2 receptors and alpha 1-, alpha 1A- and alpha 1B-adrenoceptors represent the minor receptor populations. The largest portion of the dopamine receptors is represented by the dopamine1 subtype, and the alpha 1B subtype dominates the alpha 1-adrenoceptor group. A heterogeneity of the distribution patterns of the different receptors throughout the basal forebrain regions is found. A comparison of the patterns shows that alpha 1-adrenoceptors have a similar regional distribution to that of the muscarinic2 receptors, but both receptor types have reciprocal distributions compared with the 5-hydroxytryptamine1 receptors. The results indicate that one transmitter may exert different effects in the basal forebrain regions depending on the densities of the respective receptor subtypes. Moreover, similar or reciprocal distribution patterns of some, but not all, analysed receptors point to a non-random association (co-distribution) of the different transmitter systems in the basal forebrain regions.

Animals↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗