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Biomedical subjects

O Bugiani

Publications and source records attributed to O Bugiani.

At least 127 records · Page 7Linked to original sources
PubMed1976

Fucosidosis: a neuropathological study.

The involvement of the central nervous system in fucosidosis is related to severe lesions of both nerve and glial cells. The morphology of cells degeneration is characterized by both vacuoli containing water-soluble fuco-derivatives (fuco-oligosaccharides) and/or granular substances probably constituted by fuco-sphingolipds. The cerebral cortex is the most severely affected. The involvement of the white matter is related to the glial cells degeneration. The relationship between the morphology of nerve and glial cells lesions, and the accumulation of oligosaccharides and sphingolipids following the absence of alpha-L-fucosidase, is briefly discussed.

Brain↗
PubMedDate not supplied

Apoptosis-mediated neurotoxicity induced by beta-amyloid and PrP fragments.

The neurotoxic activity of beta-amyloid (beta A) and prion protein (PrP) fragments contributed to the hypothesis concerning a causal role of amyloid deposits in Alzheimer disease (AD) and in prion-related encephalopathies. In this study, we investigated some aspects of the molecular mechanisms associated with neurotoxic activity of synthetic peptides homologous to beta A (beta 25-35) or PrP (PrP106-126) fragments. Chronic (5-7 d) exposure to both peptides induced neuronal death by apoptosis, as suggested by biochemical and morphological analysis. The apoptotic mechanism was confirmed by ultrastructural examination. The intracellular cascade of events activated by peptides was investigated by Northern blot and PCR analysis of expression of early genes (c-fos, c-jun, c-myc) and other proteins (p53, SGP-2 bcl-2, HSP70, Ich-1) potentially involved in apoptosis. With the exception of bcl-2 mRNA decrease and a slight increase of SGP-2 in PrP106-126-treated cells, no consistent alterations of these mRNA expressions were found in neuronal cells exposed to beta 25-35 or PrP106-126. Furthermore, we synthesized amidated homologs of both peptides with low amyloidogenic activity to test directly the relationship between amyloid fibrils and cell death. The neurotoxicity exhibited by PrP106-126-NH2 was similar to that observed with original peptide, whereas the amidation of beta 25-35 partially reduced the neurotoxicity of this peptide.

Alzheimer Disease↗
PubMedDate not supplied

Changes in excitability of CA1 pyramidal neurons in slices prepared from AlCl3-treated rabbits.

Intracellular recordings in 'in vitro' hippocampal slices, prepared from intracisternally AlCl3-intoxicated rabbits, were obtained from 43 CA1 pyramidal neurons. The experiments were performed 12-20 days after aluminum administration. The electrotonic length was significantly shorter than that of 33 control neurons, in agreement with morphological evidence of an Al-induced dendritic impairment. Both postsynaptic and Ca2(+)-dependent K+ hyperpolarizing potentials were also found to be significantly decreased, with reciprocal enhancement of excitatory postsynaptic potentials and depolarizing after-potentials. The former finding is ascribed to a selective neurotoxic effect of aluminum on GABAergic interneurons; the latter can be accounted for by an Al-induced increase in cyclic AMP, which is known to block the Ca2(+)-activated K+ conductance responsible for after-hyperpolarizing potentials. It is concluded that aluminum can exert its epileptogenic effect through multiple neurotoxic mechanisms involving membrane electrotonic properties, K+ conductances, and synaptic influences, thus resulting in a neuronal hyperexcitable state. Such changes are detectable in the early stages of the Al-induced encephalopathy, when there is only slight evidence of cytoskeleton alterations (i.e., neurofibrillary degeneration).

Action Potentials↗
PubMedDate not supplied

Intracellular mechanisms mediating the neuronal death and astrogliosis induced by the prion protein fragment 106-126.

Prion encephalopathies include fatal diseases of the central nervous system of men and animals characterized by nerve cell loss, glial proliferation and deposition of amyloid fibrils into the brain. During these diseases a cellular glycoprotein (the prion protein, PrP(C)) is converted, through a not yet completely clear mechanism, in an altered isoform (the prion scrapie, PrP(Sc)) that accumulates within the brain tissue by virtue of its resistance to the intracellular catabolism. PrP(Sc) is believed to be responsible for the neuronal loss that is observed in the prion disease. The PrP 106-126, a synthetic peptide that has been obtained from the amyloidogenic portion of the prion protein, represents a suitable model for studying the pathogenic role of the PrP(Sc), retaining, in vitro, some characteristics of the entire protein, such as the capability to aggregate in fibrils, and the neurotoxicity. In this work we present the results we have recently obtained regarding the action of the PrP 106-126 in different cellular models. We report that the PrP 106-126 induces proliferation of cortical astrocytes, as well as degeneration of primary cultures of cortical neurons or of neuroectodermal stable cell lines (GH(3) cells). In particular, these two opposite effects are mediated by the same attitude of the peptide to interact with the L-type calcium channels: in the astrocytes, the activity of these channels seems to be activated by PrP 106-126, while, in the cortical neurons and in the GH(3) cells, the same treatment causes a blockade of these channels causing a toxic effect.

Amino Acid Sequence↗
PubMedDate not supplied

Nerve cell loss in the progressive encephalopathy induced by aluminum powder. A morphologic and semiquantitative study of the Purkinje cells.

The injection of aluminum powder into the cerebrospinal fluid induces a slowly progressing encephalomyelopathy with cerebellar atrophy. We have studied the changes in the cerebellar cortex in order to establish whether Purkinje cell loss takes place. The rabbits were killed by perfusion with paraformaldehyde and glutaraldehyde at intervals from 3 to 85 days after injection of aluminum. Changes were observed in all animals killed between 12 and 85 days after the injection. Neurofibrillary degeneration with 10 nm neurofilaments was observed in the perikaryon of Purkinje cells. The neurofibrillary tangles extended into the proximal part of the dendrites and of the axons. A time-related deterioration of the Purkinje cells was observed. These cells appeared atrophic with eccentric and shrunken nuclei and with dark cytoplasm. By electron microscopy debris of Purkinje cell perikarya, dendrites and axons were found. The semiquantitative analysis revealed a time-related loss of Purkinje cells. Atrophy of the molecular and granule cell layers was observed. A marked proliferation of glial cells contrasted with the severe neuronal losses. Such findings may be relevant to several human diseases in which the central nervous system is exposed to aluminum over long periods of time.

Aluminum↗
PubMedDate not supplied

Ventral root axonopathy and its relation to the neurofibrillary degeneration of lower motor neurons in aluminum-induced encephalomyelopathy.

The injection of metallic aluminum (Al) into the cerebrospinal fluid of adult rabbits induces neurofibrillary degeneration of lower motor neurons. We studied the ventral roots and the corresponding motor neurons of Al-treated animals to clarify the modality and extent of reaction of the axon in relation to the severity of perikaryonal involvement. Moreover, the involvement of dorsal root ganglion cells was compared to that of lower motor neurons. Rabbits received 0.15 ml of a 1% Al slurry intracisternally and were perfused through the heart with aldehydes at 14-62 days after injection. Spinal cords and roots were embedded in Epon and examined morphologically and by morphometric techniques. An axonopathy was observed in the ventral roots, characterized by neurofilamentous axonal swellings and myelin attenuation in several size classes of axons. Results obtained from axons traced in serial sections indicate that there may be a unifocal or a multifocal axonopathy. Dorsal root ganglion cells showed milder changes by comparison with motor neurons and their axons in the ventral roots. The most severe axonopathy was associated both with an incidence of 66-81% of motor neurons showing neurofibrillary degeneration and with a rapidly progressing motor weakness. These findings are related in the discussion section to the pathological expression of human neurological disorders in which the lower motor neurons are selective targets.

Aluminum↗
PubMedDate not supplied

Burst suppression and impairment of neocortical ontogenesis: electroclinical and neuropathologic findings in two infants with early myoclonic encephalopathy.

We report the electroclinical and neuropathologic correlations in 2 children aged 2.5 months affected by early myoclonic encephalopathy characterized by epileptic seizures, erratic myoclonus, and an EEG pattern of burst suppression. Despite different etiologies, the neuropathologic findings showed similar abnormalities in both cases, with no substantial impairment of the myelination processes. Islands of matrix tissue scattered in the periventricular region and neurons aligned marginally in the bulbar olives were detected. The presence of numerous large spiny neurons dispersed in the white matter along the axons of the cortical gyri was the most striking finding. The neurons have been interpreted as abnormally persisting interstitial cells in 2.5-month-old children. These early generated neurons, normally present during neocortical histogenesis, are programmed to die near the end of gestation or soon after birth. The interstitial cells are regarded as a waiting compartment of afferent fibers during cortical development. Their persistence in our patients represents an anatomic condition for cortical disconnection providing a pathophysiologic basis to burst-suppression phenomena.

Brain↗