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Biomedical subjects

V Bigl

Publications and source records attributed to V Bigl.

At least 91 records · Page 5Linked to original sources
PubMed1991

Alzheimer's disease: a monoclonal antibody raised against paired helical filaments.

Paired helical filaments (PHF) were isolated from the cerebral cortex of patients with Alzheimer's disease (AD) by a combination of SDS treatment and density gradient centrifugation according to the method of Ihara et al. (1983). The protein component of the preparation was extracted with formic acid and Balb/c mice were used for immunization. Hybridoma supernatants were screened by immunocytochemical staining, by an ELISA assay, and by immunoblotting of SDS-PAGE, the latter both using the PHF preparation as antigen. One hybridoma which showed a strong reactivity with PHF in both the ELISA assay and immunocytochemistry was then used to produce ascites fluid in Balb/c mice. Antibodies reacted immunocytochemically with neurofibrillary tangles and neurites involved in plaque formation in AD but did not show a cross-reaction to human control brain and rat brain. The results indicate that the antibody which has been raised reacts with an antigen component of PHF.

Alzheimer Disease↗
PubMed1990

The cholinergic system and memory: amelioration of ethanol-induced memory deficiency by physostigmine in rat.

Male Sprague-Dawley rats were treated with a solution of ethanol (20% v/v) as the only source of fluid for 28 weeks while controls received tap water. Profound reductions of acetylcholine content, the activities of choline acetyltransferase and acetylcholinesterase and choline uptake were observed in the cortex, hippocampus, substantia innominata and striatum four weeks after withdrawal from ethanol. These changes in cholinergic markers were accompanied by an impaired performance in a spontaneous alternation task tested at long acquisition-retention intervals. This ethanol induced behavioural deficiency, which most likely represents a memory impairment, could be reversed by application of physostigmine (0.45 g/kg; i.p) whereas neostigmine did not show any behavioural effect. The results suggest that ethanol-induced memory impairment can be ameliorated by pharmacological manipulation of central cholinergic function.

Acetylcholine↗
PubMed1989

Effect of early visual pattern deprivation on development and laminar distribution of cholinergic markers in rat visual cortex.

In order to evaluate the role of cholinergic cortical mechanisms in the shaping of visual cortical plasticity in more detail the present paper summarizes recent studies on the laminar distribution of muscarinic acetylcholine receptors, choline acetyltransferase, and sodium-dependent high-affinity choline uptake sites during postnatal ontogenesis of the visual cortex of monocularly derived rats using autoradiographic techniques as well as quantitative biochemical methods after separating the different cortical layers by a cryocut technique. The data are correlated to the laminar distribution of cholinergic fibers within the visual cortex as studied by the immunohistochemical visualization of choline acetyltransferase. The laminar distribution of cholinergic receptor binding in the visual cortex changes during ontogenesis. In adult rats, the highest muscarinic acetylcholine receptor density is found in layer I. The activity of the choline acetyltransferase is rather uniformly distributed in all cortical layers. Adult activity values are reached at the age of 25 days. In adult rats the enzyme activity is highest in layer V. In all visual cortical layers the highest 3H-hemicholinium-3 binding to choline uptake sites during the postnatal period studied is already detectable at the age of 10 days, then binding decreases sharply until day 25 at which age it nearly equals the value found in the adult brain. Binding sites exhibit highest density in layers I and IV of the adult rat visual cortex. Monocular deprivation resulted in significant changes in all three parameters studied with different cortical laminae preferentially affected. The data suggest that the normal laminar development of the modulatory function of cholinergic transmission in the rat visual cortex depends on the presence of physiological light stimulation.

Aging↗
PubMed1989

The ontogeny of benzodiazepine receptors in selected regions of the rat brain: effect of perinatal exposure to diazepam.

The postnatal development of the binding of [3H]flunitrazepam to benzodiazepine receptors has been studied in the frontal cortex, cerebellum, striatum, hypothalamus and hippocampus of the rat after prenatal, perinatal and postnatal exposure to diazepam. The dams were injected subcutaneously with single daily doses of 1 mg/kg of diazepam from day 7-20 of gestation or from day 15 of gestation day 6 after birth. Offspring of untreated dams were injected in the same way from postnatal day 7-20. The developmental profiles of the binding of [3H]flunitrazepam obtained in both control and diazepam-treated groups of animals were very similar. This supported the idea of a sequential development of benzodiazepine receptors in relation to the different rates of maturation of certain structures of the brain. Prenatal administration of diazepam resulted in an increase of the binding of [3H]flunitrazepam in the frontal cortex by 20% at postnatal day 90 and in a decrease of binding in the hippocampus by 14% at postnatal day 60 and an increase of binding by 18% at postnatal day 90. Perinatal exposure to diazepam did not affect the binding of [3H]flunitrazepam in the hippocampus in young adult offspring. Postnatal application of diazepam resulted in a transiently decreased binding of [3H]flunitrazepam in the cerebellum by 20% at postnatal day 28. The results obtained point to the necessity for a prolonged evaluation of events after exposure to diazepam in early stages of development of the brain.

Animals↗
PubMed1989

Adaptive changes in the central noradrenergic system in monocular deprived rats.

Noradrenaline and dopamine content, K+-stimulated release of 3H-noradrenaline, 3H-noradrenaline high-affinity uptake, 3H-prazosin and 3H-rauwolscine binding to alpha 1- and alpha 2-adrenoreceptors, respectively, were studied in isolated visual structures (visual cortex, superior colliculus, lateral geniculate nucleus) of three-month-old rats monocularly deprived by unilateral eyelid closure at postnatal day 11. Monocular deprivation resulted in a number of changes in comparison with normal littermates, mainly in the lateral geniculate nucleus, both ipsilateral and contralateral to the closed eye. K+-stimulated release of noradrenaline and high-affinity noradrenaline uptake were significantly increased, 3H-rauwolscine binding to alpha 2-adrenergic receptor sites was decreased in the contralateral and ipsilateral lateral geniculate nucleus. 3H-Prazosin binding to alpha 1-adrenergic receptors as well as the levels or noradrenaline and dopamine in the lateral geniculate nucleus were unaffected by monocular deprivation. The data support the suggestion that the lateral geniculate nucleus plays a key role in modulating visual information processing and that the lack of an adequate visual input within the first weeks of life interferes mainly with the development of the noradrenergic system at the level of the lateral geniculate nucleus.

Animals↗
PubMed1988

Amyloid deposition in the nucleus basalis of Meynert complex: a topographic marker for degenerating cell clusters in Alzheimer's disease.

The deficiency of the cholinergic cortical projection system arising in the different basal forebrain structures collectively referred to as nucleus basalis of Meynert complex is a constant finding in Alzheimer's disease, a disorder which is neuro-pathologically characterised by the appearance of three intracerebral formes of twisted beta-pleated sheet (amyloid) fibrils, neurofibrillary tangles, amyloid-containing neuritic plaques and congophilic amyloid angiopathy. In the present study the quantitative relationship between these hallmarks of the disease, amyloid deposition and neuronal loss in the cholinergic basal forebrain system, was investigated in ten cases of Alzheimer's disease. Besides a constant involvement of the cerebral cortex and hippocampus, all cases of Alzheimer's disease show a large amount of amyloid in the medial septal nucleus, in the diagonal band nucleus and in the substantia innominata which is correlated with neuronal loss in these areas. These amyloid deposits in the basal forebrain are due to congophilic angiopathy associated with plaques and neurofibrillary tangles. The distribution of amyloid deposition in the basal forebrain is restricted entirely to those neuronal clusters which represent the origin of cholinergic innervation of the cerebral cortex and hippocampus. Immediately adjacent structures are not affected. These findings suggest a pathogenetic role of amyloid deposition in the mechanism of degeneration of the cholinergic basal forebrain system.

Aged↗
PubMed1988

The ontogeny of GABA receptors and glutamic acid decarboxylase in regions of the rat brain. Effect of prenatal exposure to diazepam.

The postnatal development of the binding of [3H]muscimol to both high-affinity and low-affinity GABA receptors and of the activity of glutamic acid decarboxylase has been studied in the frontal cortex, cerebellum, striatum and hypothalamus of the rat, after prenatal exposure to diazepam. The dams were injected subcutaneously with single daily doses of 1 mg diazepam/kg from day 7-20 of gestation. The developmental profiles of the binding of [3H]muscimol to high-affinity GABA receptors were very similar in both control and diazepam-treated offspring. Prenatal administration of drug revealed no significant alteration in the binding of [3H]muscimol. The results in controls supported the concept of a sequential development of this population of GABA receptors in relation to the different maturation of structures in the brain. For the study of low-affinity GABA receptors, the dams were treated in the same way and, additionally, 1 mg diazepam/kg/day was injected subcutaneously in the offspring from postnatal day 5-10. At postnatal days 21 and 90, no qualitative or quantitative differences in the binding of [3H]muscimol to low-affinity GABA receptors in control and diazepam-exposed groups of animals were observed. The developmental profiles of the activity of glutamic acid decarboxylase were qualitatively very similar in the four areas of the brain studied. Prenatal exposure to diazepam revealed a transient elevation of the activity of the enzyme up to 33% in the frontal cortex, the cerebellum and the hypothalamus in the first postnatal week. The possible functional significance of these alterations is discussed.

Animals↗
PubMed1988

A critical period of the development of beta-adrenergic receptor binding in the visual system of rat during visual deprivation.

The density of [3H]dihydroalprenolol binding to beta-adrenergic receptors in the visual structures (visual cortex, superior colliculus and lateral geniculate nucleus) of rats raised under a normal 12 hr light-dark cycle was compared to those of rats visually deprived at different postnatal ages. Unilateral eyelid suture from postnatal days 10 or 16 to 3 months resulted in an increased [3H]dihydroalprenolol bilateral binding in the lateral geniculate nucleus compared to control animals. Monocular deprivation from postnatal days 25, 40, 60 and 90 had no effect on the density of [3H]dihydroalprenolol binding. After re-opening of the eyelid, which was sutured on postnatal day 10, at postnatal day 25 no changes in beta-adrenergic receptor binding in the lateral geniculate nucleus of the adult animal could be detected. After re-opening of the sutured eyelid on day 90, followed by examination of the adrenoceptor density 4 weeks later, the [3H]dihydroalprenolol binding in both lateral geniculate nuclei remained elevated as was also found in corresponding regions of monocular deprived animals. Binocular visual deprivation from postnatal day 10 until the age of 3 months had no effect on [3H]dihydroalprenolol binding in the visual centres in comparison to corresponding control animals. The data suggest that there exists a critical period for the ontogenetic development of beta-adrenergic receptors binding in the visual system of rats during which permanent alterations of receptor binding can be induced by monocular but not binocular visual deprivation.

Aging↗
PubMed1988

Noradrenergic sprouting and beta-adrenergic receptor binding in the lateral geniculate nucleus of rats after unilateral visual cortex ablation.

One and two weeks after unilateral visual cortex (VC) ablation beta-adrenergic receptor binding is increased in the lateral geniculate nucleus (LGN) of both sides. 6 month later beta-receptor binding in the LGN is decreased again and no differences to untreated control animals are detectable. Using the glyoxylic acid fluorescence method for the visualization of amines a transient increase in the density of noradrenergic fibers in the dorsal part of the ipsilateral LGN can be demonstrated with a maximum 2 weeks after VC ablation. With longer survival time noradrenergic fibre density in the ipsilateral dorsal LGN (LGNd) decreases again and one year after the operation only few fluorescent fibres can be observed in the lateral part of the LGN compared to untreated control animals. Histologically an increased gliosis in the ipsilateral LGNd develops following removal of the visual cortex. In addition, degenerative changes in nerve fibers and terminals as well as neuronal degenerative changes are present and are most pronounced in the medial part of the ipsilateral dorsal LGN. Electron microscopically degenerating terminals in the dorsal part of the ipsilateral LGN can be identified as cortical afferents. Using potassium permanganate fixation typical noradrenergic axons with small dense core vesicles can be demonstrated in the LGN. In the denervated LGNd (i.e. the ipsilateral LGNd after visual cortex ablation) axon terminals with dense core vesicles appear exhibiting the structural peculiarities of growth cones seen during ontogenesis. They could be regarded as ultrastructural equivalent of the newly formed noradrenergic sprouts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The cholinergic system in aging.

A morphometric analysis of neuronal loss during normal aging was performed in the nucleus basalis Meynert complex of the basal forebrain (Nbm) (nucleus septi medialis, nucleus of Broca's diagonal band, nucleus basalis) and the ciliary ganglion, a peripheral cholinergic structure, in patients free of neurological and psychiatric illness. As a basis for morphometric evaluation of the Nbm complex, a three-dimensional reconstruction of this complex structure was made. Neuronal counts in the Nbm complex and the ciliary ganglion remained stable up to the age of 60 or 50 years, respectively. After this age the number of neurons declined moderately in ciliary ganglion in all cases studied as well as in the Nbm complex in some cases (-20 and -25%, respectively, at about 90 years of age). In 3 out of 8 cases older than 60 years, neuronal counts in the Nbm complex were not reduced, so that no significant decline in neuronal number is apparent from the mean values of the 17 cases studied. No age-related changes were found in the neuronal distribution amongst the different subgroups of Nbm neurons using the alternative nomenclature of Mesulam et al. [J. comp. Neurol. 214: 170-197, 1983]. Our results provide no evidence that the cortical cholinergic projection system and peripheral cholinergic neurons might be especially vulnerable during normal aging. The severe degeneration of the cholinergic cortical projection system in SDAT is probably caused by mechanisms different from those acting during normal aging.

Adult↗
PubMed1986

Dark-rearing affects the development of benzodiazepine receptors in the central visual structures of rat brain.

The postnatal development of [3H]flunitrazepam binding to benzodiazepine receptors has been studied in the retina, lateral geniculate nucleus, superior colliculus, frontal cortex and visual cortex of the rat. In the frontal and visual cortices, binding reached the highest level at postnatal day 25 and then decreased slightly until adulthood. In the superior colliculus, the adult value of [3H]flunitrazepam binding is already reached at postnatal day 25, whereas in the retina the highest binding was found at postnatal day 50. The ontogeny of benzodiazepine binding sites in the visual regions does not essentially differ from that in other brain regions, suggesting that the appearance of [3H]flunitrazepam binding sites in the visual system is not correlated with the development of retinal function and the functional maturation of the visual system with regard to processing of light stimuli. Raising rats in complete darkness from birth until the age of 25 days resulted in significantly decreased binding levels in the lateral geniculate nucleus and in the superior colliculus by 29% and 17%, respectively, as compared to controls. [3H]Flunitrazepam binding in the other regions studied was not affected by dark-rearing. Presumably, the complete lack of visual experience interferes with the functional development of GABAergic mechanisms involved in the gating function of the subcortical visual centres for visual information transfer.

Age Factors↗
PubMed1986

Development of glutamate binding sites in the visual structures of the rat brain. Effect of visual pattern deprivation.

The postnatal development of the Na-independent 3H-glutamate binding sites has been studied in the retina, lateral geniculate nucleus, superior colliculus, frontal and visual cortex of the rat. In the visual cortex, lateral geniculate nucleus and superior colliculus the highest binding was found at postnatal day 15. Until day 25 glutamate binding decreases drastically reaching the adult values. In contrast, in the retina and in the frontal cortex binding exhibits a maximum already at postnatal day 10 and then decreases to reach the adult value at day 25. Comparing glutamate binding within the visual areas and frontal cortex, highest binding was found in the lateral geniculate nucleus at all stages of age studied. Unilateral eyelid closure from day 11 postnatally resulted in a decreased binding level in the lateral geniculate nucleus ipsilateral to the sutured eye of both 25- and 90-day-old monocularly deprived rats in comparison to controls. A decreased glutamate binding was also observed in the retina of both eyes of 90-day-old monocularly deprived animals, which was not detectable in rats monocularly deprived only until the age of 25 days. The other regions studied were not affected by monocular deprivation. In contrast to that, monocular deprivation until postnatal day 90 failed to affect glutamate high-affinity uptake in both retinas. Binocular deprivation had no effect on glutamate binding in the retina of adult rats. Since monocularly deprived rats use their open eyes for longer periods of time than animals with both eyes open [1], the decreased glutamate binding in the lateral geniculate nucleus might be the consequence of a down-regulation of the increased functional activity of the cortico-geniculate pathway of the non-deprived (open) eye. The decreased glutamate binding in the retina of both eyes of monocularly deprived animals suggests a physiological coupling between both retinas and/or central nervous control of retinal glutamatergic mechanism.

Animals↗
PubMed1985

Benzodiazepine receptors in the visual structures of monocularly deprived rats. Effect of light and dark adaptation.

In 25-day-old rats with one eyelid sutured at the age of 10 days, the binding of [3H]flunitrazepam in the visual structures (retina, lateral geniculate nucleus, superior colliculus, visual cortex) and frontal cortex was determined. Monocular visual deprivation (MD) resulted in a significant decrease of the [3H]flunitrazepam binding in the retina of the open eye to about 76% of the control value. No changes in [3H]flunitrazepam binding were detectable under these conditions in the central visual structures examined and the non-visual cortical region. Scatchard analysis indicated that the changes found in the retina of the open eye of MD rats are due to a decreased binding affinity only, the maximum receptor number being unaffected. Eight hours after re-opening the sutured eyelid of 25-day-old MD rats, benzodiazepine binding in the open eye was increased to the control level, whereas the binding in the retina of the re-opened eye remained unchanged in comparison to control animals. Dark adaptation of 25-day-old control rats resulted in an increased [3H]flunitrazepam binding in the retina by 28% compared to that detectable in the retina of light-adapted animals. In contrast, dark-adaptation of MD rats did not affect [3H]flunitrazepam binding in the retina of both eyes in comparison to that found in the corresponding retina of light-adapted MD animals. The data obtained suggest a physiological coupling between both retinas, possibly mediated through centres inside of the central nervous system.

Animals↗
PubMed1985

Neuronal loss in different parts of the nucleus basalis is related to neuritic plaque formation in cortical target areas in Alzheimer's disease.

In order to substantiate the hypothesis of a cholinergic pathogenesis of neuritic plaques in Alzheimer's disease the relationship between the loss of cholinergic neurons in six subdivisions of the nucleus basalis of Meynert and density of neuritic plaques in five neocortical target areas and hippocampus was studied in five cases with Alzheimer's disease. Distribution of plaques in different cortical areas as well as degeneration pattern of neurons within the subpopulations of the nucleus basalis were markedly different in the cases of Alzheimer's disease. Quantitative evaluation of the number of neuritic plaques in the five cortical areas revealed a strong correlation with the loss of neurons in those subpopulations of the nucleus basalis which give rise to the cholinergic innervation of the affected cortical areas. The nonlinearity of this correlation may reflect two different modes of plaque formation. Either plaque formation is a self-perpetuating process with an increasing rate depending on the number of plaques already formed or additional mechanisms, with an increasing rate of influence during plaque formation are induced. The shape of the regression function is different for the various cortical regions and their corresponding subpopulations of the nucleus basalis suggesting a different dependency of neuritic plaque formation on the neuronal loss in the nucleus basalis. This might reflect a different density of cholinergic fibers within these areas, a different degree of collateralization of the fibers or other factors not yet known. The findings indicate that degeneration of cortical cholinergic afferents from the neurons of the nucleus basalis is an important feature in the pathogenesis of neuritic plaques.

Aged↗
PubMed1984

Correlation between cortical plaque count and neuronal loss in the nucleus basalis in Alzheimer's disease.

In order to substantiate the hypothesis of a cholinergic matrix for neuritic plaque formation in Alzheimer's disease (AD), the relationship between the loss of cholinergic neurons in the basal forebrain and formation of neuritic plaques in the cerebral cortex was studied in 5 cases of neuropathologically verified AD. Quantitative evaluation of the number of neuritic plaques in the cerebral cortex as calculated from 6 areas showed a strong correlation with the loss of neurons in the nucleus basalis of Meynert (NbM). This finding indicates that changes in cortical cholinergic innervation which arise from the neurons of the NbM are an important feature in the pathogenesis of neuritic plaques.

Acetylcholinesterase↗
PubMed1984

Neurone loss in the nucleus basalis of Meynert in Creutzfeldt-Jakob disease.

In a man of 47 with a 2-month history of Creutzfeldt-Jakob-disease verified neuropathologically a morphometric study of the nucleus basalis of Meynert, the major source of cholinergic innervation of the cortex, revealed a neuronal loss of 45%. The degeneration of these neurones may provide the morphological substrate of the cortical cholinergic deficiency which has been reported in this condition. The six subpopulations of the nucleus basalis were affected in different degrees. Neuronal loss was most pronounced in those subpopulations which project to cortical areas most affected by spongiosis and neuronal loss. It is suggested that maintenance of the nucleus basalis complex is a necessary condition for higher cortical function.

Basal Ganglia↗