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C Bertoni-Freddari

Publications and source records attributed to C Bertoni-Freddari.

At least 55 records · Page 3Linked to original sources
PubMed1992

Enlargement of synaptic size as a compensative reaction in aging and dementia.

A quantitative investigation has been carried out on synaptic contact zones of dentate gyrus supragranular layer and cerebellar glomeruli in autoptic samples from adult, old and demented patients. During physiological aging and senile dementia, the synaptic average area was significantly increased as compared to adult values in both the CNS areas investigated. Conversely, the number of contacts and their total surface contact area per unit volume of tissue were decreased. Current literature reports that, in animal models, enlarged synapses undergo perforations and splitting to modify synaptic connectivity. As against these assumptions, the increased synaptic size observed in our study appears to represent a compensative reaction of old and demented CNS to counteract the reduction in number and in total contact area of the synaptic junctions.

Aged↗
PubMed1990

Morphological adaptive response of the synaptic junctional zones in the human dentate gyrus during aging and Alzheimer's disease.

A computer-assisted morphometric study has been carried out on ethanol phosphotungstic acid (E-PTA) stained synaptic junctions in the human dentate gyrus supragranular layer from adult, old and Alzheimer's disease (AD)-affected patients. The number of synapses per unit volume of tissue (Nv = numerical density), the average area of the single junction (S) and the total area of the synaptic contact zones in a unit volume of tissue (Sv = surface density) were the 3 parameters taken into account. The synapse to neurone ratio was also calculated for each patient. During physiological aging, Nv and Sv significantly decreased and S increased, respectively. In the AD hippocampi, Nv and Sv underwent a further decrease which was in the range of more than 40% with reference to the adult values. S was the same as the old control group. In comparison with the adult values, the number of synapse/neurone decreased by 15.6 and 48% in old and AD patients, respectively. Nv, S and Sv, while reporting on discrete ultrastructural features of the synaptic junctional zones, are closely related to each other and, taken together per group of patients, may represent a reliable index of the morphological adaptive changes taking place at the synapses. Thus, the significant increase of S both in old and AD hippocampi may be regarded as a CNS plastic response to aging and disease, although the marked decrease of Nv and Sv supports that in AD synaptic ultrastructural alterations proceed beyond a critical threshold for functional recovery.

Aged↗
PubMed1989

Computer-assisted morphometry of synaptic plasticity during aging and dementia.

A computer assisted morphometric study has been carried out on synaptic membranes in the dentate gyrus supragranular layer and cerebellar glomerulus from adult, old and demented patients. Numerical (Nv) and surface (Sv) densities as well as average area (S) of the synaptic contact zones were calculated directly on electron microscopic negatives by means of an ASBA (Wild Leitz, AG) image analyzer properly programmed. The results showed a decrease of Nv in both the CNS areas investigated during aging and, to a higher extent, in senile dementia. S was found to be significantly increased in old and demented CNS as compared with adult values. In the old hippocampus Sv was decreased by 40% whereas no significant difference was present between old and adult cerebellum; in senile dementia this parameter underwent a significant decrease in both areas investigated. We interpret the present findings in terms of morphological remodelling capability of the synaptic junctional zones during aging and disease.

Aged↗
PubMed1989

Quantitative morphology of the zinc-iodide-osmium (ZIO) stained synaptic vesicles.

A computer assisted morphometric method has been elaborated to quantify synaptic vesicles evidenced by means of the Zinc-Iodide-Osmium (ZIO) staining procedure in nerve endings of a very discrete area of the cerebellar granular layer: the glomerulus. The following parameters were calculated directly on electron microscopic negatives of 4.67 microns 2 of surface terminal area: number of vesicles per unit area (Na), and per unit volume (Nv), volume density (Vv), average diameter (d) and average volume of the single vesicle (V). Ultrastructural changes taking place at nerve endings also cover synaptic vesicles, thus quantitative studies regarding vesicle population at synaptic regions can be correlated to functional changes occurring in the process of chemical transmission and reflect the plasticity of synaptic junctional zones. Although this histochemical staining method generally is referred to as unspecific, after comparing our data with the available literature reports, we propose that ZIO-positive vesicles could have a physiological significance. These ZIO-positive organelles could take part in the intraterminal homeostatic control of Ca++ ions.

Animals↗
PubMed1988

Age-dependent deterioration of neuronal membranes and the pathogenesis of Alzheimer's disease: a hypothesis.

Senile dementia of the Alzheimer's type (SDAT) is considered either a specific pathological condition unrelated to normal aging or an accumulation of brain aging alterations leading to clinical dysfunction. In the present paper a hypothesis is formulated to reconcile these two issues to a common denominator, i.e. the increased age-dependent deterioration of the neuronal membrane. If this holds true, normal aging and SDAT may be considered as two different aspects of the same problem and specific interventions to slow down the former can delay the onset of the latter to older ages.

Aging↗
PubMed1988

Quantitative morphology of synaptic plasticity in the aging brain.

Quantitation of synaptic ultrastructural changes is of great importance in neurobiology, since merely qualitative alterations, if not extreme, are not readily detectable. In the present paper we discuss our previous and present findings on the number (numerical density: Nv), size (average length of the synaptic profiles: L) and surface contact area (surface density: Sv) of the synaptic junctions in aging rodent and human brains. We found that number and size of the synapses are in a close inverse relationship so as to maintain the total surface contact are among the nerve cells constant. These three parameters are closely related to each other, their quantitation may thus represent a reliable index of the morphological aspects of synaptic plasticity, i.e. the modification of ultrastructure occurring at synaptic membranes after transient changes in synaptic activity. During aging, the morphological plasticity of synapses appears to be seriously impaired: the number of synapses and the total surface contact area among the nerve cells are markedly reduced. However, old nerve cells seem to retain the ability to modify their synaptic endings and to partially compensate for the reduced surface density of the contact zones by expanding the average size of the persisting junctions. Our recent studies on synaptic plasticity in human brains from old and demented subjects showed that while the size of the synaptic contacts remains constant, the numerical and surface densities undergo a further decrease in demented brains relative to that in normal aging.

Adult↗
PubMed1987

The effect of chronic hydergine treatment on the plasticity of synaptic junctions in the dentate gyrus of aged rats.

The number of synapses (Nv), the surface density of contact zones (Sv) as well as the average size (S) of E-PTA stained synapses in the supragranular layer of the dentate gyrus from adult (12 months), old (30 month), and Hydergine-treated old (30 months) rats were measured by using quantitative morphometric techniques. In old animals, Nv and Sv were significantly reduced, whereas S was significantly increased as compared with the values in adult rats. Hydergine (Codergocrine mesylate) treatment of old animals (3 mg/Kg/day for 4 weeks) influenced these three parameters, differentially. The Sv in aged animals receiving Hydergine, relative to that in untreated old rats, was significantly increased; the number and size of synapses in the treated old rats were significantly higher and smaller, respectively, than that in old controls. We interpret the present findings to indicate a modulating effect of Hydergine on the morphological plasticity of synaptic junctions in the dentate gyrus of aged rats.

Aging↗
PubMed1986

Quantitative investigation of the morphological plasticity of synaptic junctions in rat dentate gyrus during aging.

The morphological plasticity of synaptic junctions was investigated by means of quantitative stereology in the dentate gyrus supragranular layer of young (3 months), adult (12 months) and old (30 months) female Fisher 344 rats. The numerical (Nv) and surface (Sv) density and the average surface area (S) of EPTA-stained synaptic junctions were calculated on 100 EM pictures per age group. We found that Nv significantly increased between the young and adult group and decreased in old animals when compared both to 3 and 12 months of age. Sv was unchanged in young and adult rats, whereas it underwent a significant reduction in the old group. The percentage distribution of S showed that at 3 months of age the majority of the synaptic population had an average size ranging between 0.12 and 0.20 micron 2, whereas during adulthood and aging there was a shift towards smaller and larger synaptic contacts, respectively. Taking into account Nv, Sv and S all together per age group, the present findings demonstrate that the morphological aspect of synaptic plasticity is markedly influenced by time and that during aging it undergoes a serious impairment. The possible involvement in memory and learning processes of these synaptic age-related morphological adaptations and the fact that the investigated junctions are supposed to be cholinergic is discussed.

Aging↗
PubMed1986

Vitamin E deficiency alters the in vivo Rb+ discrimination of rat brain cortical cells.

The in vivo Rb+ uptake and release of rat brain cortical cells of 11-months-old rats fed with a vitamin E deficient diet was investigated. The animals were treated with a daily dose of 30 mg RbCl/100 g body weight for 14 days. After discontinuation of the RbCl treatment the animals were killed at intervals of 2, 4, 9 and 15 days, respectively. The intracellular Rb+ and K+ contents were analyzed by energy dispersive X-ray microanalysis, whereas concentrations of these two ions were determined by atomic absorbtion spectrophotometry in the serum and cerebrospinal fluid. Vitamin E deficient rats accumulate more Rb+ than age-matched normally fed animals at any time taken into account. Rb+-discrimination ratios calculated on the basis of Rb+ and K+ contents of both, cortical cell cytoplasm and cerebrospinal fluid, are higher in vitamin E deficient rats than in the controls (+20%), which supports the view that the enhanced membrane lipid peroxidation induced by vitamin E deficiency impairs the passive membrane permeability for Rb+ (and K+).

Aging↗
PubMed1986

Age-related morphological rearrangements of synaptic junctions in the rat cerebellum and hippocampus.

A quantitative investigation has been carried out on the age-related morphological changes of the synaptic junctions in the cerebellar glomeruli and in the supragranular layer of the hippocampal dentate gyrus of young (3 months), adult (12 months) and old (28-30 months) rats. The numerical (Nv) and surface (Sv) density as well as the average length (L) of E-PTA stained synapses was calculated by means of morphometric methods. The results we obtained showed a similar trend in both these areas of the CNS. Nv significantly increased between young and adult rats and significantly decreased in the old group, when compared both to young and adult animals. Sv appeared to be unchanged comparing young and adult animals, whereas it was significantly reduced in the old group. L showed a decrease between 3 and 12 months of age and appeared to be markedly increased in the old animals when compared to adult values. From the present findings it can be inferred that number (Nv) and size (L) of the synapses are in a close inverse relationship which, through the organism's life span, aims to maintain the constancy of the surface contact area (Sv) among the dendritic network. By considering Nv, L and Sv altogether per age group, we were able to obtain a reliable measurement of the morphological aspect of synaptic plasticity through different periods of the life. With regard to aging we found that, despite the 'compensative synaptogenesis' brought about by the increased size (L) of the synaptic appositions, the reactive capacity of old nerve cells is seriously impaired.

Age Factors↗
PubMed1985

Amiloride inhibits the PHA-evoked mouse splenic lymphocyte proliferation.

The present study was aimed to ascertain whether Na+ influx can be involved in regulation of blastogenesis and proliferation of PHA stimulated mouse splenic lymphocytes. The cells were cultivated in the presence of different concentrations of amiloride, an inhibitor of passive Na+ influx, and cellular activation was monitored by 3H-thymidine incorporation and blast index determination. The drug was not toxic and inhibited cell growth in concentrations ranging from 1 X 10(-3) to 1 X 10(-5) mmol/ml. The results are in agreement with the hypothesis that Na influx is necessary for PHA evoked mouse splenic lymphocyte activation.

Amiloride↗
PubMed1985

Chronic dietary choline modulates synaptic plasticity in the cerebellar glomeruli of aging mice.

A morphometric investigation was carried out on ethanolic phosphotungstic acid (E-PTA) stained synaptic junctions in the cerebellar glomeruli of adult, old, old choline-deficient and old choline-supplemented mice. Numerical (Nv) and surface (Sv) density as well as average length (L) of the synapses were calculated on 100 pictures per group. A significant reduction of Nv and Sv, as well as an increase of L was found during aging. Choline deficient animals did not show any change as compared to old animals of the same age. In choline supplemented mice Nv and Sv were significantly increased and L significantly decreased, respectively, as compared to old control littermates. No difference was found between adult and choline supplemented mice. In the cerebellar glomeruli only a small fraction of fibers are cholinergic, therefore the present findings support the idea that dietary choline can influence systems other than cholinergic. The possible role of choline supplementation in the modulation of synaptic plasticity via the synthesis and/or turnover of neuronal membrane choline phospholipids, is discussed.

Animals↗
PubMed1985

A modulating effect of Hygergine on the synaptic plasticity of old rats.

The morphological plasticity of E-PTA stained synaptic junctions was investigated by means of quantitative morphometry in the dentate gyrus supra-granular layer of adult, old and old-Hydergine treated rats. Numerical (Nv) and surface (Sv) density as well as average size of the synapses (S) were the three parameters considered. During aging, Nv and Sv significantly decrease whereas S increases. Hydergine treatment to old rats resulted in a significant increase of Nv and Sv and a significant decrease of S. Present findings are interpreted as a modulating effect of Hydergine on the synaptic plasticity of old rats.

Aging↗
PubMed1984

Effect of chronic vitamin E deficiency on the synapses of cerebellar glomeruli in young rats.

A morphometric investigation has been carried out on the synaptic junctions in the cerebellar glomeruli of young-adult rats chronically deprived of vitamin E for 10 months and control animals of the same age. The following parameters were evaluated: the average length of the synapses (L), the numerical (NV) as well as the surface (SV) density of the synaptic contact zones. The results from these experimental groups were compared with data from young, adult and old rats. The results obtained show a significant decrease of the surface density of the synaptic contact zones in old and alpha-tocopherol deprived young-adult (11-month-old) rats as compared to younger and normally fed animals. This reduction of the synaptic contact area seems to be due to the marked decline in the number of synapses found in both cases. The average size (L) of the synaptic junctions, on the other hand, was increased in alpha-tocopherol deficient rats as compared to normally fed littermates. The significant reduction of the synaptic contact area in old and vitamin E deprived young rats supports the hypothesis that a common denominator may be responsible to explain this alteration. Because of the recognized protective role of alpha-tocopherol against free radical attacks on plasma membranes, the present findings support an involvement of membrane structural alterations in aging as well as in vitamin E deficiency.

Aging↗
PubMed1984

Amiloride inhibition of triiodothyronine stimulated hepatocyte proliferation in vivo, and involvement of the intracellular Na+ content in mitotic regulation: an X-ray microanalytic study.

Energy dispersive X-ray microanalysis was carried out on the nuclei of hepatocytes stimulated to proliferate by the injection of a pharmacological dose of triiodothyronine (T3). The Na+ content displayed a continuous time-dependent increase in T3 stimulated animals. The Cl- concentration followed the same pattern as did the sodium, but its increase was lower. In contrast to Na+ and Cl- concentrations, the alteration in K+ content displayed a slight but statistically significant decrease at 8 h and 16 h from T3 injection and returned to the control levels by 22 h. The modifications of the Na+ and K+ content of the nuclei are reflected in their Na+:K+ molar ratios. A positive correlation was found between the increase of this parameter and the DNA synthesis rate of T3 stimulated hepatocytes. Amiloride was able to inhibit the stimulatory effect of the hormone, blocking the increase of both the intranuclear Na+:K+ ratio and of the DNA synthesis rate of hepatocytes. The findings are consistent with the hypothesis that a high Na+ content is associated with mitogenesis and, moreover, that an increased Na+ influx plays a causal role in regulating cell proliferation.

Amiloride↗
PubMed1983

In vitro block of murine L 1210 leukemia cell growth by amiloride, an inhibitor of passive Na+ influx.

The present study was aimed to decide whether Na+ influx can be involved in regulation of murine L 1210 leukemia cell growth. Cells were cultivated in the presence of different concentrations of amiloride and cellular growth was monitored by 3H-thymidine incorporation/10(5) cells. This drug inhibited cell growth in concentrations ranging from 1 X 10(-5) to 1 X 10(-3) mmol/ml. Even short time treatments with amiloride caused irreversible alterations: the cells, although survived, lost their ability to divide. The results support the hypothesis that Na+ influx is necessary for the duplication of tumor cells.

Amiloride↗
PubMed1983

Alterations of the synaptosomal membrane 'microviscosity' in the brain cortex of rats during aging and centrophenoxine treatment.

Synaptosomal and myelin fractions were isolated from the brain cortex of young, adult and old male CFY rats (2, 12 and 24 mth, respectively). The purity of the fractions was tested by transmission electron microscopy and marker enzyme assays. The cholesterol content of the fractions was also determined. Samples of the fractions were labelled with diphenylhexatriene (DPH) and the fluorescence anisotropy (r) of the label was measured at various optical densities. The values of r extrapolated to zero optical density were compared in the age groups and used for calculating the 'microviscosity' of the membranes. The 'microviscosity' of synaptosomal membranes displayed a significant age-dependent increase: from 2.3 +/- 0.02 (SD) in the young group it increased to 2.6 +/- 0.03 poise by the age of 24 mth at 37 degrees C. Most of this increase occurred between the adult and old age. The cholesterol content of the synaptosomes also increased significantly during aging. Centrophenoxine (CPH)-treatment with 100 mg/kg body weight daily dose for 2 mth was able to reverse the age-dependent alterations of both the membrane 'microviscosity' and the cholesterol content in the synaptosomes: the values returned nearly to the adult level. The results obtained are interpreted in terms of the membrane hypothesis of aging attributing to primary role to the free-radical induced membrane damage in cellular aging.

Aging↗