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B Ghetti

Publications and source records attributed to B Ghetti.

At least 181 records · Page 10Linked to original sources
PubMed1986

Monoaminergic nerve terminals in the cerebellar cortex of Purkinje cell degeneration mutant mice: fine structural integrity and modification of cellular environs following loss of Purkinje and granule cells.

The cerebellar cortex of normal and Purkinje cell degeneration mutant mice was examined by electron microscopy after fixation with potassium permanganate for the demonstration of small granular vesicles in monoaminergic nerve terminals. In control mice, monoaminergic terminals were found mainly in apposition to Purkinje cell dendrites. After the degeneration of Purkinje cells, which constitute the major target for monoaminergic fibres in the cerebellum, monoaminergic terminals persisted in the cerebellar cortex of Purkinje cell degeneration mutant mice. They were ensheathed by astroglial processes in most of the instances. They were also apposed to boutons that contained agranular vesicles, and to stellate cells in the molecular layer. Clear synaptic specializations in the form of thickening of the synaptic membranes were not observed in either control or mutant mice. It is hypothesized that the survival of monoaminergic axons following loss of their target cells may be attributed to the lack of intimate adhesion to their target elements, to a possible functional interaction with the glia, or to the integrity of the extracerebellar terminal fields of the monoamine axon collaterals.

Adrenergic Fibers↗
PubMed1986

Transplantation of ventral mesencephalic anlagen to hosts with genetic nigrostriatal dopamine deficiency.

Attempts to reconstruct the damaged nigrostriatal pathway in experimental models of Parkinson disease have thus far been carried out in animals with neurotoxically induced dopamine deficiency. The present study establishes the weaver (wv/wv) mutant mouse as a genetic model of chronic striatal dopamine denervation by demonstrating a marked decrease of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra pars compacta. Moreover, grafts of embryonic ventral mesencephalon taken from genetically normal mice and transplanted into the lateral ventricle of adult weaver mutants can survive and grow in the mutant host environment, express tyrosine hydroxylase immunoreactivity, and reinnervate the target regions of the recipient. These results provide evidence of integration of graft and host tissue and suggest that transplantation of dopamine neurons may be effectively applied to overcome nigrostriatal degeneration of genetic etiology.

Animals↗
PubMed1985

Residual benzodiazepine (BZ) binding in the cortex of pcd mutant cerebella and qualitative BZ binding in the deep cerebellar nuclei of control and mutant mice: an autoradiographic study.

In mutant mice 'Purkinje cell degeneration' (pcd), there is an almost complete degeneration of Purkinje cells followed subsequently by a partial degeneration of granule cells. Recent neurochemical studies have revealed a 50% decrease in benzodiazepine (BZ) receptors in 45-day-old pcd mutants after degeneration of the Purkinje cells. At 300 days there is an 80% decrease in BZ receptors concomitant with granule cell losses. To determine the histological localization of these receptor changes this autoradiographic analysis was conducted. An in vitro autoradiographic technique was used to explore [3H]flunitrazepam binding. BZ receptors were found to be more concentrated in the molecular than the granular layer of mutant and control cerebellar cortices. There was, nonetheless, no statistically significant difference in grain counts between control and mutant mice in any layer. Substantial atrophy of cerebellar structures, particularly of the molecular layer, occurred in the mutant mice. It began even before 45 days of age but was extreme at 300 days. When the appropriate mathematical correction factor was introduced for the layer atrophy there was a 60% decrease in grain count in 45-day-old mutants in the molecular layer and a 84% decrease in 300-day-old mutants compared to controls. The initial decrease in total BZ receptors in the 45-day-old mutant animals is associated with a selective loss of Purkinje cells. The amount of receptor binding which persists in the 300-day-old mutants in the molecular layer would appear to reflect binding in the remaining parallel fibers from granule cells which remain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Cerebellar plaques in familial Alzheimer's disease (Gerstmann-Sträussler-Scheinker variant?).

A large kindred, with two brothers coming to autopsy, of a syndrome consisting of ataxia, dementia, and some Parkinsonian features is reported; inheritance appears to be autosomal dominant. Neuropathologically, there were plaques and neurofibrillary tangles in the cerebral cortex as well as some in the basal ganglia, particularly reminiscent of the plaques seen in Kuru; there was only minimal spinal cord disease (pyramidal tract field). The problems of classifying this condition--Alzheimer's disease with cerebellar involvement or other entities, such as the Gerstmann-Sträussler-Scheinker condition (1936), especially now that transmission to animals in the latter has been reported--are discussed. Some relevant theoretical considerations derived from animal work, particularly in scrapie, are also reviewed.

Alzheimer Disease↗
PubMed1985

Induction of neurofibrillary tangles in cultured mouse neurons by maytanprine.

Neurofibrillary (neurofilament) tangles were induced in cultured neurons of newborn mouse dorsal root ganglia by exposure to maytanprine, an anti-microtubule drug. By 12-24 h of treatment, small short neurofilament bundles were found in the neuronal perikarya and proximal portions of the neurites. By 48-72 h of treatment, small neurofilament bundles were assembled into larger masses, and after 72 h and onward several neurofilament bundles coalesced into single large distinctive perinuclear rings in the neuronal perikarya. A histometric analysis of maytanprine treated axons demonstrated that the density of microtubules decreased rapidly, while that of neurofilaments decreased more slowly. As a result of microtubule depolymerization by maytanprine treatment, neurofilaments change their distribution pattern in neuronal perikarya and subsequently form tangles.

Animals↗
PubMed1985

Progressive dialytic encephalopathy and the problem of aluminum neurotoxicity.

Some clinical, epidemiological, and pathological aspects of the progressive dialytic encephalopathy have been considered with the aim to clarify the nature of the disease as well as to identify factors that possibly favor the neurotoxic effect of aluminum in uremic patients. The role of the blood-brain barrier has been outlined. The concept of a delayed neurotoxicity of aluminum has been introduced to face the problem of the risk of mental deterioration and neuromyopathies in patients on oral aluminum administration. A comparison has been made with the dementias of the Alzheimer type and with amyotrophic lateral sclerosis in which aluminum is regarded as a possible etiologic factor. Finally, a proposal has been made of monitoring aluminum levels in blood serum and cerebrospinal fluid as well as the results of electrodiagnostic tests, CT scan, and language and psychometric examinations, that may help in clarifying the problem of aluminum neurotoxicity in uremic patients.

Aluminum↗
PubMed1983

Comparative immunocytochemical characterization of neurofibrillary tangles in experimental maytansine and aluminum encephalopathies.

The neurofibrillary tangles induced by maytansine and aluminum are stained by the peroxidase-anti-peroxidase method, using antibodies raised against the 68, 150 and 200 kdaltons polypeptide subunits of normal neurofilaments. The immunoreaction with each of the 3 antisera occurs regardless of the location of the neurofilament accumulation, whether in perikarya, dendrites or axons. It is very likely that the filaments of the neurofibrillary tangles induced by both aluminum and maytansine contain all the 3 neurofilament subunits.

Aluminum↗
PubMed1983

Loss of Purkinje cell-associated benzodiazepine receptors spares a high affinity subpopulation: a study with pcd mutant mice.

In order to identify the relative number of benzodiazepine (BZ) receptors in Purkinje and granule cells, the Purkinje cell degeneration (pcd) mutant mouse was used at different ages. In these mice, Purkinje cells have degenerated almost completely by 45-50 days of age. Granule cell loss occurs only later, and is most severe between 180 and 300 days. [3H]Flunitrazepam (FNZ) and [3H]ethyl-carboline-3-carboxylate (beta-CC) were used as ligands. In the 45-50-day-old pcd mice, it was found that there is approximately a 50% decrease in the number of receptors as labeled by [3H]beta-CC or [3H]FNZ, when the binding is expressed as fmol/cerebellum. The binding decreased by approximately 80% in 300-day-old pcd mice (fmol/cerebellum). [3H]FNZ was not displaced by 1 microM RO5-4864, ruling out binding to glial cells. Nonlinear regression analysis of FNZ saturation data provided evidence for two populations of receptors (high and low affinity sites). Only the low-affinity sites were reduced in number at 45 days. [3H]beta-CC saturation data showed, however, only one population of receptors. The total number of receptors (Bmax) was significantly lower for beta-CC than for FNZ in the control mice. It appears that 50% of the total BZ receptors is associated with Purkinje cells. In addition, our data on 300-day-old pcd mutants strongly suggest the existence of granule cell-associated BZ receptors.

Animals↗
PubMed1983

Neurofibrillary changes in human brain. An immunocytochemical study with a neurofilament antiserum.

Brain samples from cases of Alzheimer's disease, postencephalitic Parkinson's disease, progressive supranuclear palsy, amyotrophic lateral sclerosis, and Pick's disease, as well as from a case of Alzheimer's disease with a large number of Hirano bodies, were stained with the peroxidase-anti-peroxidase method using an antiserum previously shown to immunoreact with normal neurofilaments and neurofilament polypeptides. The specificity of this serum was confirmed by absorption an purified neurofilament proteins. Neurofibrillary tangles of Alzheimer's disease, postencephalitic Parkinson's disease, and progressive supranuclear palsy, Pick's bodies, and the fibrillary inclusions of amyotrophic lateral sclerosis were all immunostained. Hirano bodies showed no immunostaining. Thus, with the exception of the Hirano bodies, all the neuronal fibrillary inclusions examined appeared to share common antigenic characteristics. The orgin of all these structures from normal neurofilaments is postulated.

Amyotrophic Lateral Sclerosis↗
PubMed1982

Progressing encephalomyelopathy with muscular atrophy, induced by aluminum powder.

The injection of aluminum powder into the cerebrospinal fluid of adult rabbits induced a slowly progressing encephalomyelopathy characterized at first by alteration of posture and then by myoclonic jerks and muscle weakness. Neurofibrillary degeneration was the hallmark of the disease and involved most of the gray areas. Giant axonal swellings were also numerous, particularly in the proximal axonal segment of neurons of the anterior horns. In the anterior horns the number of neurons with neurofibrillary degeneration decreased with time, while the images of neuronophagia increased in number in the rabbits killed in the second and third month after aluminum injection. In these animals there were also pathologic changes in the peripheral nerves and muscles. The peripheral nerve showed wallerian-like degeneration. Furthermore, in some animals, the presence of nodal axonal swellings and of paranodal myelin retraction were expression also of a distal axonopathy. Neurogenic muscular atrophy appeared in animals sacrificed in the second and third month after injection.

Aluminum↗
PubMed1982

Dopamine deficiency in the weaver mutant mouse.

The dopamine system in weaver mutant mice (B6CBA-Aw-J/A background) was studied. Dopamine was 27% lower in the olfactory tubercle, 77% lower in the frontal cortex, and 75% lower in the striatum of 6-month-old weaver mice compared to control mice of the same age. Norepinephrine and serotonin were not lower in these brain areas. Tyrosine hydroxylase activity in the striatum was measured with a radiometric assay and was 70% lower in weaver mice. Examination of mice from 11 to 180 days of age revealed that the dopamine system failed to develop in weaver mice. Motor activity in individual animals was assessed using circular photocell activity cages with minimal illumination. Apomorphine and pergolide, direct dopamine agonists, increased activity more in weaver mice than in normal littermates. Amphetamine, which releases endogenous stores of dopamine, was less active in mutant mice. These findings provide suggestive evidence that postsynaptic dopamine receptors in weaver mutants might have become supersensitive as a result of lower levels of dopamine in motor areas of the brain. Anatomical evidence of dopamine system abnormalities was found in weaver mice by examination of serial sections cut from the midbrain of mutant and normal mice. The pars compacta of the substantia nigra in weaver mice appeared hypocellular when compared with the corresponding sections from controls. Fewer large neurons were seen in the affected animals. This study illustrates that weaver mice have specific deficiencies in the dopamine system. The weaver mouse might provide a way of examining the biochemical and behavioral effects of long term dopamine deficiency and a way to examine drugs to treat dopamine-deficient states in vivo.

Animals↗
PubMed1981

Human brain protein phosphorylation in vitro: cyclic AMP stimulation of electrophoretically-separated substrates.

In vitro phosphorylation of electrophoretically-separated brain proteins was studied in human frontal cortex obtained 3-16 h post-mortem from 13 patients ages 3 days-82 years with extensive, mild or no neuropathological involvement. In 12 of the 13 cases, cyclic AMP increased incorporation of phosphate into acid-precipitable protein. Analysis of the autoradiographic profiles of separate proteins indicated that phosphorylation of the doublet of molecular weight 86-80,000 was stimulated by cyclic AMP in certain samples. This doublet corresponded to the cyclic AMP stimulated doublet from rat frontal cortex we have termed band D-1,2 (proteins Ia and Ib of Ueda and Greengard). Of special interest was the fact that, while co-migration was observed in the other phosphoprotein bands studied, band D-1,2 of humans consistently migrated slightly less than rat protein band D-1,2. This difference was not a function of post-mortem time, subcellular fraction or buffer used in the reaction phosphorylation assay. The use of post-mortem tissue was not a contributing factor as the retardation in band D-1,2 migration was still observed when post-mortem rat brain was used for comparison. In two human post-mortem samples, there was no measureable band D-1,2 phosphorylation even in the presence of cyclic AMP. This was the case in both homogenate and crude synaptosome/mitochondrial preparations. Band F-1 (mol. wt. = 47,000) was not observed in any of the human samples studied. This is consistent with prior studies in rat which show that band F-1 phosphorylation is not detected in post-mortem brain, Band F-2 (mol. wt. 41,000) recently identified as pyruvate dehydrogenase, was lightly phosphorylated under the reaction conditions used in this study.

Aged↗
PubMed1981

Exaggerated cyclic AMP accumulation and glial cell reaction in the cerebellum during Purkinje cell degeneration in pcd mutant mice.

The Purkinje cell degeneration mutant (pcd) is characterized by a complete loss of cerebellar Purkinje cells. Norepinephrine causes an accumulation of cyclic AMP in the cerebellum of pcd that is far greater than in normal mice. Experiments were conducted 1) to correlated changes in the cyclic-nucleotide response with a histologic examination of the cerebellum during neuronal loss and 2) to examine the role of cyclic AMP catabolism and adenosine receptor interactions in the phenomenon. The greatest elevation in cyclic AMP occurred between 30 and 128 days of age when a severe astrocytic response was demonstrated throughout the cerebellar cortex. Purkinje cells had degenerated by 45 days of age. Norepinephrine elicited a smaller increase in cyclic AMP from 155-day-old mice than at earlier ages, and the response continued to decrease with age; at 270 days, equal accumulation, and at 365 days. lower accumulation of cyclic AMP was detected in pcd cerebella. During this time, the Purkinje cell debris had been removed, the granule cell layer was depleted of granule cells, and the molecular layer was deprived of a large number of parallel fibers. However, although phagocytosis of neuronal debris was completed, large numbers of astrocytic processes were still seen in the neuropil. Biochemical experiments in vitro established that the exaggerated accumulation of cyclic AMP in the presence of norepinephrine was not due to lower catabolism of cyclic AMP, a synergistic interaction with adenosine, or a result of lower protein in the pcd cerebellum. The correlates of heightened norepinephrine-stimulated accumulation of cyclic AMP with neuronal loss and the glial cell reaction might indicate that cyclic nucleotides play a role in controlling some glial cell functions, ie, proliferation, migration, and phagocytosis.

Animals↗
PubMed1981

Purkinje cell loss and the noradrenergic system in the cerebellum of pcd mutant mice.

Purkinje cells in the cerebellum receive inhibitory noradrenergic input from the locus coeruleus. In pcd mutant mice all Purkinje cells degenerate by 45 days of age. The purpose of the present studies was to determine if the loss of these cerebellar neurons affects the amounts of norepinephrine in the cerebellum of mice 25-280 days of age. No significant changes in norepinephrine content were detected during or after Purkinje cell degeneration. However, since degeneration led to a reduction in cerebellar weight, the norepinephrine concentration was increased in pcd mutants. These results indicate that despite the loss of a major postsynaptic target (Purkinje cells), the cerebellar noradrenergic input remains stable.

Age Factors↗
PubMed1980

Neurofibrillary degeneration in cultured adult mouse neurons induced by maytansine.

The effects of maytansine, an antimitotic compound isolated from an African plant, were studied by light and electron microscopy in dissociated cell cultures of adult mouse dorsal root ganglia. Maytansine at 10-100 ng/ml concentration caused reversible, concentration-dependent, inhibition of microtubule assembly and induction of a large amount of 10 nm filaments in the cytoplasm of cultured neurons and Schwann cells.

Animals↗
PubMed1980

Exaggerated norepinephrine-stimulated accumulation of cyclic AMP in vitro in cerebellar slices from pcd mutant mice following Purkinje cell loss.

Norepinephrine caused in vitro an accumulation of cylic AMP in slices of the cerebellum from pcd mice which was 300 percent greater than in cerebella from age-matched, heterozygous, normal mice. Purkinje cells had disappeared in the pcd mice at the time when the exaggerated hormonal response was seen. The data indicate that high cyclic AMP accumulation can take place in cerebellar cells other than Purkinje cells.

Animals↗
PubMed1980

Cyclic AMP-dependent protein kinase activity in human brain across age.

Cyclic AMP-dependent protein kinase activity was measured in the cerebral cortex of humans 2 days to 83 years of age and in the cortex of F344 rats 3, 22, or 30 months of age. Protein kinase activity was detected in the human brain, but no age-related differences in activity were observed in the presence or absence of cyclic AMP. Age differences were also not seen in protein kinase in the rat cerebral cortex. Enzyme activities in rat and human brain were similar.

Adult↗