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Background:Laryngeal carcinoma involving anterior vocal commissure (AVC) represents a great challenge for staging and treatment.

Summary We have previously shown that prolonged alcohol ingestion leads to neuronal loss in the supraoptic nucleus of the rat and that the surviving neurons, mainly the vasopressinergic ones, display marked increase in volume. In an attempt to establish correlates for the volumetric alterations we have studied the organelles of supraoptic nucleus neurons in three groups of rats-ethanol-fed, pair-fed, and dehydrated, in all cases treated from 2 to 12 months of age. The volume and surface area of the rough endoplasmic reticulum and Golgi apparatus, and the volume of nucleoli and neurosecretory granules were estimated on the basis of the respective volume and surface densities. The volumes and surface areas of all quantified organelles were increased in both alcohol-fed and dehydrated animals, although the increases were greater in the former group. Changes in the organelles studied are commonly regarded as reliable indicators of the neurosecretory activity of magnocellular neurons. Thus, our results suggest that under conditions of chronic alcohol exposure, the synthesizing activity of the surviving supra-optic neurons is augmented to compensate for the alcohol-induced neuronal loss and/or as a consequence of the alcohol-induced hyperosmolality. Changes in the transport and release of the neurosecretory material cannot, however, be ruled out as an additional cause of neuronal enlargement.

Summary We have recently shown that in spite of the absence of receptors for gonadal steroids in the supraoptic nucleus (SON) of the rat hypothalamus, the volume of the nucleus and the size of its neurons are larger in males than in females, and that these differences between male and female rats are correlated with body weight and dependent on the vasopressinergic neurons. As supraoptic neurons and their organelles enlarge when they are engaged in active peptidergic secretion we have carried out a morphometric ultrastructural analysis to determine if cell structures involved in the synthesis and storage of neurosecretory material also display weight-dependent sex dimorphism. Groups of six male and six female rats aged 30,60 and 180 days were used. Nucleoli, rough endoplasmic reticulum and neurosecretory granules were analysed and we estimated their volume or surface densities and the total volume of nucleoli and rough endoplasmic reticulum, and total surface area of rough endoplasmic reticulum. We found that, with the exception of neurosecretory granules, the densities of the organelles did not differ among the groups studied, but total values were higher in males. These differences were found to be weight-dependent. Since the organelles studied are regarded as reliable indicators of the neurosecretory activity of supraoptic neurons, our data fully support the view that the weight-dependent sexual dimorphism observed in this nucleus reflects greater synthetic activity of its vasopressinergic neurons associated with the need to maintain water balance in larger bodies.

Summary Past work on the C.N.S. of nutritionally deprived immature rats shows widespread structural and functional alterations that were not found in nutritionally deprived adults. In the present work we studied cerebellar mossy fibre terminals of adult rats, given a 8% casein diet for periods of 6, 12 and 18 months. After 12 months of the diet, mossy fibre terminals presented a large number of spherical or disc-shaped membrane-free inclusions herein referred to as presynaptic inclusions, with diameters up to 1.3 µm and formed by fine-textured subunits, compacted into 3 nm strands. This material is an extension of the cytoplasmic network of the terminal. No special relationship was observed with the active zones; synaptic vesicles found in the proximity or embedded in these inclusions were often of the flat type, whereas those close to the active zones always appeared spherical. These results show that even in adult rats synaptic terminals are areas sensitive to protein deprivation.

The influence that thyroid hormones have on the development of the cerebellar cortex is well known. Their absence in adults leads to important functional changes probably related to abnormalities in nerve terminal activity, although no morphological alterations have hitherto been described. Using ultrastructural morphometric methods, we have studied the effects of thyroidectomy on the cerebellar cortex mossy fiber terminals of adult rats with different survival periods. No significant changes in the volume and surface area of these terminals were found. The numbers of synaptic vesicles in groups 7, 15 and 30 days after thyroidectomy were significantly greater than in controls. A significant increase in coated pit formation was found when thyroidectomized groups were compared with controls. This increase is due to the lack of thyroxin since it can be counteracted by thyroxin administration. Whether this increased coated pit formation is a membrane retrieval mechanism or is related to the uptake of extracellular molecules remains to be determined.

Lipofuscin deposition in nerve cells is one of the most reliable and consistent neurocytological features correlated with ageing. Purkinje cells of long-term alcoholfed rats show large agglomerates of lipofuscin granules after six months of alcohol experiment, whereas in normal biological ageing, this happens only after 25 months of age. Cerebellar interneurons have specific patterns of lipofuscin accumulation during ageing concerning both its morphological type and chronology of deposition. We studied the effects of chronic alcohol treatment on cerebellar interneurons taking particular account of lipofuscin pigment accumulation. Control and alcohol-fed groups for 1, 3, 6, 12 and 18 months were used. A precocious and progressive accumulation of lipofuscin granules occurred in granule, Golgi and basket cells. Stellate cells remained pigment-free. The lipofuscin deposited in the granule and Golgi cells was of the granular type, whereas that of basket and stellate cells was lamellar (fingerprint-like pattern). These results parallel those observed during normal ageing, and reinforce the hypothesis of the existence of a close relationship between chronic alcohol consumption and precocious nerve cell ageing.

The association connexions of the peri-auditory (SF, Ea and INS) and auditory (AI, AII and Ep) areas of the cat cortex were studied in silver impregnated material of 32 experiments with cortical lesions.

Biopsy fragments from the frontal cortex of three patients with subacute sclerosing panencephalitis (SSPE) were studied by light- and electronmicroscopy. Special attention was given to the neuropil. Electron-dense degenerating dendrites were observed in all cortical layers, more abundantly in layers I, II, and III. Mitochondria, with electron-dense deposits between disrupted cristae, were often recognized within these dendrites. The deposits were enzymatically extracted by pronase. These findings are in keeping with recent alterations found in dendrites of patients with other cerebral disorders, and they may be related to the mental changes seen in SSPE.

Biopsy fragments from the frontal cortex of two patients with early forms of subacute sclerosing panencephalitis (SSPE) were studied with ultrastructural methods. Special attention was given to mitochondrial abnormalities observed in dendrites from the three superficial cortical layers. Some of the mitochondria presented atypical elongated cristae parallel to the longer axis of the organelle and closely apposite each other. The surface of these cristae is undulated, and the intracristal space is regularly septate. As these abnormal mitochondria appeared in dendrites, which in later stages of the disease are supposed to degenerate, it is advanced that these abnormalities could be precursors of dendritic changes and be possibly related to the precocious, insidious mental changes which characterize the early forms of the disease, as it is known that the disruption of the dendritic domain is linked with neuronal dysfunction.

Biopsy fragments from the frontal cortex of one patient with SSPE were studied with ultrastructural methods. Special attention was given to the presence of neurofibrillary tangles observed in all cortical layers. These tangles were composed either of filaments with a diameter of 10–12 nm or of paired helical filaments 22–24 nm at their widest and periodically reduced to 10 nm about every 80 nm. These tangles were observed in all cortical layers, while those formed by single filaments were only visualized in layer 3. The simultaneous appearance of both types of tangles in the same patient suggests that they may be chemically related, which is in keeping with recent chemical data concerning the nature of the neurofilament protein subunit.

Golgi studies of three cortical biopsies from patients with SSPE reveal an abnormal pyramidal dendritic domain spine-loss, and reactive gliosis. These findings support results obtained in a previous ultrastructural study of this disease, and are in keeping with the pathological features observed in other situations in which mental changes occur.

We have recently shown that lengthy periods of low-protein feeding of the adult rat lead to deficits in the number of hippocampal granule and pyramidal cells, and in the number of mossy fiber synapses. These findings prompted us to analyze the dendrites of these neurons to evaluate whether, under the same experimental conditions, degenerative and/or plastic changes also take place at the dendritic level. The hippocampal formations from five 8-month-old rats fed a low-protein diet (casein 8%) for 6 months from the age of 2 months and from five age-matched controls were Golgi-impregnated and the morphology of the dendritic trees quantitatively studied. We found that in malnourished animals there was a reduction in the number of dendritic branches in the dentate granule cells and in the apical dendritic arborizations of CA3 pyramidal neurons. In addition, in the dentate granule cells the spine density was markedly increased and the terminal dendritic segments were elongated in malnourished animals. No alterations were found in the apical dendrites of CA1 pyramidal cells. The results obtained show that long periods of malnutrition induce marked, although not uniform, changes in the dendritic domain of the hippocampal neurons, which reflect the presence of both degenerating and regrowing mechanisms. These alterations are likely to affect the connectivity pattern of the hippocampal formation and, hence, the activity of the neuronal circuitries in which this region of the brain is involved.

We have previously demonstrated that prolonged low-protein diet leads to irreversible cell loss in the hippocampal formation of the adult rat. Because the extent of the resulting hippocampal synaptic alterations is not well characterized, we studied the contacts between mossy fibers and the dendritic excrescences of CA3 pyramidal cells (MF-CA3 synapses) using quantitative methods. Moreover, we investigated whether rehabilitation from undernutrition would influence the morphology of hippocampal synapses. To address these issues, three groups of adult rats were compared: (a) rats fed with a normal diet for 12 months (control rats); (b) rats treated during the same period with low-protein diet (undernourished rats); and (c) rats undernourished for 6 months and then switched to normal diet for 6 months (recovery rats). Timm staining and electron microscopy were employed to estimate the volume of the mossy fiber system and the number and related quantitative features of MF-CA3 synapses. The volume of the suprapyramidal bundle of the mossy fiber system and its total number of synapses were smaller in undernourished rats than in control and recovery animals. These parameters did not differ between the latter two groups. The size of mossy fiber terminals and dendritic excrescences and the surface area of synapses were smaller in undernourished than in control and recovery groups. Conversely, in recovery animals, the volume of the suprapyramidal bundle of the mossy fiber system, the size of mossy fiber terminals and dendritic excrescences, and the total number and surface area of synapses were similar to those of controls. These findings indicate that, following rehabilitation, the pre- and postsynaptic compartments of MF-CA3 synapses undergo structural alterations which compensate for the neuronal loss induced by undernutrition.

Exposure of rats to sustained stress has been associated with behavioural impairments, the degree of impairment being greater with increasing age of the subject. Although the behavioural deficits have been frequently attributed to stress-induced neuronal loss in the hippocampus, the validity of that view may be disputed since it is based on data collected using conventional morphometric methods which are subject to bias. The question of whether stress per se does indeed induce hippocampal cell losses was therefore re-examined using unbiased stereological tools in the present work. Specifically, we used the optical fractionator and the Cavalieri principle, to respectively estimate the total number of neurons and volumes of the main divisions of the hippocampal formation of young and old rats which had been exposed for 1 month to an unpredictable stress paradigm. The efficacy of the treatment was confirmed by elevated serum corticosterone levels measured at various intervals during the experimental period. In order to evaluate whether any deleterious effects might have occurred merely due to the stress-induced elevations in corticosterone secretion, we conducted a parallel study on animals that were injected with corticosterone over a similar duration. Neither stress nor treatment with corticosterone was found to result in significant cell losses in any division of the hippocampal formation; likewise, neither treatment produced significant volumetric differences. Further, these results were not influenced by age of the experimental subjects. The present findings therefore call for a reappraisal of the hypothesis that hippocampal cell loss accounts for the behavioural impairments observed by others following prolonged stress and/or chronic elevation of serum corticosterone levels.

Large numbers of nuclear inclusions have been found in the nerve cells of the sphenopalatine ganglia of six healthy adult dogs. Their morphological characteristics are similar to those previously described elsewhere. The presence of simple and granular bodies in normal cells seems to support the hypothesis that these nuclear structures might be considered as normal nuclear organelles related to cellular metabolic activity.

Nuclear rods and sheets are described in neurons from the cerebellar cortex of rats alcoholized through ingestion of a 20 % aqueous ethanol solution over a period of 90 and 180 days. An eventual relationship between these nuclear inclusions and alcoholization is advanced.

Summary Applying a morphometric analysis, the effects of chronic alcohol consumption on Golgi-impregnated Purkinje cells from the rat cerebellar cortex were evaluated. Alcohol-fed animals received ethanol up to 1, 3, 6, 12 and 18 months and controls were given the same amount of food and an aqueous solution with sucrose replacing the ethanol isocalorifically. The following parameters of Purkinje cell dendritic trees were studied: dendritic field area, branching density, total branch length, spine density and total number of spines. Results showed a progressive decrease of all parameters in alcohol-fed animals. Significant differences were found in all rats after 12 months of alcohol intake. The reduction of the dendritic network was found to be related to a drop in mean total number of dendritic branches after 6 months of alcohol consumption. It is concluded that long-term alcohol consumption induces a decrease of the synaptic receptive area of Purkinje cells which may well lead to functional changes in the cerebellum.

Meganeurites have been described by light and electron microscopy in several neuronal lipid storage diseases. In neuronal ceroid lipofuscinosis (NCL), they appear to be less frequent.We present the first combined Golgi-electron microscopy study of a patient with NCL, which shows that the axons from neurons with meganeurites arise from their distal poles.Our results reinforce the assumption that neuronal malfunction in this disorder, as in other neuronal storage diseases, is also due to the presence of such meganeurites in the area of the axon hillock-initial axon segment.

The presence of sexual dimorphism in the hippocampal formation has long been recognized. Differences between male and female rats have been detected with respect to the number of dentate granule cells and branching patterns of dentate granule and hippocampal pyramidal cell dendrites. Groups of 6 male and 6 female Sprague-Dawley rats were studied at 180 days of age. Based on light microscopical Timm-staining and Golgi-impregnation and electron microscopy, and applying morphometric techniques, we now report that the total number of synapses between mossy fibers and the apical dendritic excrescences of CA3 pyramidal cells is the same in male and female rats, despite a higher numerical density in the latter. Moreover, the volume of the mossy fiber system was found to be smaller in females. Because the number of dentate granule cells is smaller in females than in males, the increased numerical density of synapses may be thought of as a compensatory mechanism to equalize the number of synaptic contacts between dentate granule and CA3 pyramidal cells in the two sexes. We demonstrate that an increase in the number of mossy fiber boutons in female rats is a determining factor for the sexual differences found.

Primitive neuritic plaques were observed in the inner third of the molecular layer of the cerebellar cortex of rats following chronic alcohol consumption. Neurites were indentified as dystrophic parallel fiber bouton. Amyloid material dispersed among neurites was not clearly recognized, dystrophic some fibrils were frequently seen among them. Astrocytic processes were noted in the periphery of the plaque. Microglial reaction, however, was non-existent. The rarity of these lesions in the rat cerebellum and their probable relation to long periods of alcohol consumption is discussed.

Quantitative parameters concerning synapses were studied in the cerebellar molecular layer of 4 cats using ultrastructural morphometric methods. The number of parallel fibre-Purkinje dendrite synapses was estimated to be about 200,000.

The mossy fibre ending organelles of 6 men were studied, using morphometric methods. The numerical densities of agranular, coated and dense core vesicles, as well as the number of agranular vesicles per μm2of the synaptic surface and per synapse were calculated.

Cilia in stellate neurons of the normal rat cerebellum are described. 8 cilia were observed in a total of 60 cells studied. An 8+1 pattern was found throughout their length. Furthermore, no arms, spokes or other accessory structures necessary for ciliary motion were seen. These findings make it possible to suggest that these cilia are probably without function and are related to the epithelial origin of these cells.