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B Ghetti

Publications and source records attributed to B Ghetti.

213 records · Page 12Linked to original sources
PubMedDate not supplied

The weaver mutant mouse as a model of nigrostriatal dysfunction.

The weaver mutant mouse has a genetic defect that results in the loss of dopamine neurons in the nigrostriatal pathway. Striatal tyrosine hydroxylase and dopamine content are reduced by 60-70%, and dopamine uptake is reduced by as much as 95%. Deficits in all three of these striatal dopamine markers are seen as early as postnatal d 3. The striatal dopamine systems in the weaver apparently have the ability to compensate for this dopamine deficit. Thus, in the weaver, in vitro resting release, as well as amphetamine-evoked fractional release of endogenous dopamine are increased. An additional change seen in the weaver striatum is an elevated serotonin content. These alterations may play an adaptive role in attempting to compensate for the dopamine loss. In summary, the weaver mutant mouse has dramatic deficits in the nigrostriatal pathway, but also seems to develop certain adaptive mechanisms in dopaminergic and other transmitter systems that may compensate functionally for the dopamine deficit. Thus, the weaver mouse provides a unique animal model for studying naturally induced neuronal degeneration that complements those models using surgical and pharmacological protocols.

Analysis of Variance↗
PubMedDate not supplied

Serotonin-immunoreactivity in the cerebellum of two neurological mutant mice and the corresponding wild-type genetic stocks.

Using a serotonin (5-HT)-specific antibody, we examined the 5-HTergic innervation of the cerebellum in the normal mouse (+/+) and in two neurological mutants: weaver (wv/wv), which are characterized by a genetically determined loss of granule cells, and 'Purkinje cell degeneration' (pcd/pcd), which are characterized by a genetically determined loss of Purkinje cells. In normal cerebellum, serotonin-immunoreactive (5-HT-ir) fibers are discrete and ascend to all three layers of the cerebellar cortex. Serotonin-immunoreactive fibers have a much higher density in the atrophic cerebella of both weaver and pcd mutants, where they form multidirectional contours. These anatomical findings provide a profile of 5-HT axon innervation of mouse cerebellum and extend previous neurochemical observations on the metabolic state of cerebellar 5-HT in neurological mutants.

Animals↗
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

Ventral mesencephalic grafts in the neostriatum of the weaver mutant mouse: structural molecule and receptor studies.

Mesencephalic cell suspensions were prepared from E12 wild-type (+/+) mouse embryos and stereotaxically implanted into the dorsal neostriatum of weaver mutant mice (wv/wv), which have a genetic mesostriatal dopamine (DA) deficiency. Survival of DA neurons in the grafts was documented by tyrosine hydroxylase (TH) immunocytochemistry. Axon growth was monitored by immunocytochemistry using a battery of antibody markers, and the cellular localization of structural protein and receptor RNA transcripts was studied by in situ hybridization histochemistry using [32P]oligonucleotide probes. The cell suspension grafts exhibited strong immunoreactivity for neural cell adhesion molecule (N-CAM), growth-associated phosphoprotein GAP-43, microtubule-associated protein 2 (MAP2), beta-amyloid protein precursor (beta APP), and phosphorylated neurofilament epitopes (clone SMI-31); intermediate-to-high levels of immunoreactivity were seen for synaptophysin. High levels of hybridization were found in the grafts for the RNA transcripts of GAP-43, MAP2, and isoforms beta APP695, beta APP714 and beta APP751 of the beta APP. No hybridization signal was detected in the grafts for DA D2 or neurotensin receptor mRNAs, both of which are normally expressed by nigral DA neurons. DA receptor autoradiography using the D2/D3 agonist [3H]CV 205-502 as a ligand showed no binding in the transplants, indicating an apparent abnormality of grafted cells; neurotensin binding sites, labeled with [125I]neurotensin, were visualized in the suspensions, indicating the possibility that receptors could be present but that RNA message levels might be too low to allow detection. These findings offer a molecular correlate of axonal, dendritic and structural protein expression by transplanted mesencephalic neurons; further, they suggest that specific functional properties of grafted nigral cells are maintained after transplantation, while other aspects of their cellular biology may be compromised.

Animals↗
PubMedDate not supplied

Asymmetrical cerebral atrophy in Alzheimer's disease.

In most Alzheimer patients brain atrophy seems to be symmetrical. Recent neuropsychological and brain imaging investigations suggest, however, that in some patients one hemisphere is more severely affected from the onset of symptoms. We have observed four Alzheimer patients with grossly asymmetrical cerebral atrophy at autopsy, in whom the topography of the most severe atrophy was consistent with the earliest clinical signs of focal brain damage. In the three patients who at onset had relevant language disorders, atrophy of the brain was more severe in the association areas surrounding the left sylvian fissure. In the fourth patient, who first complained of visuospatial troubles, the right, nondominant hemisphere was more affected. These clinical and pathological findings suggest that association areas of one hemisphere were involved quite early in the evolution of the disease, conceivably at the same time as the hippocampus and related limbic structures. In these patients, a morphometric analysis of cortical changes in homologous areas of the cortex (area 22) was carried out in order to investigate the effect of the evolution of the disease upon cortical changes. This analysis showed that the numerical densities of nerve cells and tangle-bearing neurons were lower on the more atrophied side and suggested that the severity of cortical atrophy might have affected the size, but not the density, of senile plaques.

Aged↗