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P Fattoretti

Publications and source records attributed to P Fattoretti.

53 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↗
PubMed1986

Impaired adaptive receptor regulation: an index of aging?

Many neuroendocrine functions are altered in old animals and their study may represent important steps in the understanding of the mechanisms of aging. A deeper insight, however, can be achieved by investigating the responsiveness to stimuli, which may reveal alterations not evident in the unstimulated conditions. At this level of study, many of such impairments have been found to be caused by receptor changes. In the present paper a third level of study is suggested in order to gain evidence of some remote failure of adaptive processes strictly linked to intimate mechanisms of aging. As at the second level of study different receptor characteristics can frequently be found at the basis of age-related alterations of biological responsiveness, at the proposed third level altered capacity of receptor regulation may be hypothesized as responsible for altered cell adaptation following hormone and drug stimuli. Experimental data are given which support this view. The possibility that receptor regulation may be used as an index of aging is suggested. This hypothesis leads to the problem of judging the validity of biological parameters deputed to represent good indices of aging. In order to solve this problem, the potential use of a mathematical model of mortality kinetics is discussed.

Adaptation, Physiological↗
PubMed1985

Thymic regulation of brain cortex beta-adrenoceptors during development and aging.

The influence of the thymus on beta-adrenoceptors has been studied in the brain cortex of mice during developing and aging. Affinity of beta-adrenoceptors shows no statistically significant changes in the various animal models investigated. Receptor density shows a fall in both athymic nude mice and in old normal mice. Receptor density, in particular, decreases progressively with advancing age. It has been demonstrated that thymus exerts a regulatory role in both development and aging, as a neonatal thymic graft is capable of reversing the receptor impairments found in young athymic nude mice and in old normal mice.

Aging↗
PubMed1982

Age-dependent decrease of beta-adrenoceptor density in the submandibular glands of mice and its modulation by the thymus.

Beta-adrenergic receptors were characterized in submandibular glands of ageing mice and old mice grafted with a neonatal thymus. No statistically significant changes of receptor affinity were found in the animal models investigated. On the contrary, receptor density showed a progressive decrease with advancing age. The age-related decrease has been found partially corrected in thymus-grafted old animals, which show a statistically significant recovery of receptor density when compared to their untreated littermates. Receptor modulation can be responsible for the age-related impairment and the thymus-dependent correction of beta-adrenergic responsiveness of submandibular glands previously observed in vivo. Hormonal balance and thyroid hormones, in particular, are suggested as being involved in the age- and thymus-dependent regulation of receptor density. In the accompanying Appendix, we describe the mathematical method used to calculate both specific and nonspecific binding from total binding data.

Aging↗
PubMed1980

[High and low affinity beta adrenergic receptor sites from submandibular glands of mice].

Beta-adrenergic receptors from submandibular glands of mice were studied by equilibrium binding experiments. Due to the fact that some discrepancies were previously observed among different author data, we compared two methods for non specific binding substruction, that represents the major source of errors in such experiments. Data were obtained strongly suggesting the presence of multiple population of binding sites and/or negative cooperativity.

Animals↗
PubMedDate not supplied

Beta-adrenoceptor changes in submandibular glands of old mice.

The hypothesis that modifications in beta-adrenergic receptors may be responsible for age-dependent change previously observed in vivo, has been investigated. Beta-adrenoceptor characteristics of submandibular glands of mice were studied by using the beta-adrenergic antagonist (-)-[3H]dihydroalprenolol. Data from such studies indicated the presence of two functional populations of binding sites in membrane preparations from young animals, displaying high and low affinity, respectively. Experiments performed on old mice membrane preparations revealed a 50% decrease in the high-affinity population receptor number when compared to the preparations from young animals. However, the affinity did not change significantly with advancing age. With regard to the low-affinity population, no statistically significant changes were observed. From these data it can be reasonably assumed that beta-adrenoceptor alteration during ageing may play a major role in the age-dependent impairment of beta-adrenergic responses in vivo.

Aging↗
PubMedDate not supplied

Electron microscopic morphometric studies on the effects of idebenone on the synaptic remodelling activity in the hippocampus and cerebellum in normal old as well as in vitamin E-deficient adult rats.

Electron microscopic morphometric investigation has been carried out on the synaptic junctions of the hippocampal dentate gyri and cerebellar glomeruli of normal, old female Wistar rats (29 months of age), and vitamin E-deficient, female adult rats (11 months of age) of the same strain. The vitamin E-deficient diet was maintained from the age of 1 month for the subsequent 10-month period. Both the normal old and the vitamin E-deficient rats were treated with a daily dose of 50 mg oxidized idebenone/kg body w/day or with its solvent (5% gum arabic) through a gastric tube during the last month before killing them. The following morphometric parameters were evaluated in the hippocampal dentate gyrus and cerebellar glomerulus: the average length of the synapses (L) the surface density (S(v)) and the numerical density (N(v)) of the synaptic contact zones. Although the idebenone treatment caused a tendency to improve these parameters in both brain compartments studied, these improvements did not reach statistical significance in the cerebellum, but did so in the case of hippocampal N(v). Vitamin E deprivation caused the usual, known alterations of the synaptic parameters. Idebenone treatment during the last month of this experiment compensated the decrease of S(v) in both the hippocampus and the cerebellum; however, its protective effect was significant only in the case of hippocampus. Idebenone effect manifests itself in the increase of L, contributing mainly to the increase of S(v), since N(v) remained practically invariate. Placebo treatments did not result in any significant alterations in the vitamin E-deficient group.

Journal Article↗
PubMedDate not supplied

Neurobiology of the aging brain: morphological alterations at synaptic regions.

Computer-assisted morphometric studies have been carried out on nerve cell terminal regions in rats of different ages. The numerical density (Nv), the average area (S) and the surface density (Sv) of ethanol phosphotungstic acid stained (E-PTA) synaptic junctions were evaluated in cerebellar glomeruli and dentate gyrus supragranular layers. The volume density (Vv), the average volume (V) and the numerical density (Nvm) of synaptic mitochondria were measured in the cerebellar glomeruli of young (3 months), adult (11 months) and old (28 months) animals. We found that during aging Nv and Sv undergo a significant decrease, whereas S is significantly increased. The mitochondrial Vv is unchanged in all the age groups analysed, whereas in old rats V is increased and Nvm decreased, respectively. We interpret our results as supporting that the old CNS retains part of its remodelling activity and is capable of adaptive morphological response at synaptic terminal regions.

Journal Article↗
PubMedDate not supplied

The effects of ageing and a vitamin E-deficient diet on the lipopigment content of rat hippocampal and Purkinje neurones.

This study examined associations between a vitamin E-deficient diet, ageing and aspects of the morphology of neuronal lipopigment in rat hippocampal and Purkinje neurones. Groups of rats given a standard diet were killed at 6, 12, 18 and 25 months of age, while a group which had received a vitamin E-deficient diet from 1-18 months were killed at 18 months of age. Lipopigment within a neuronal cell body consists of a number of discrete regions of varying size. These were identified by fluorescence microscopy and a photograph for each individual neurone was projected onto paper, so that the outlines of the discrete regions of lipopigment could be drawn and subjected to morphometric measurements. Both ageing and vitamin E deficiency in relation to hippocampal neurones and vitamin E deficiency in relation to Purkinje neurones (in which ageing effects were not examined), were associated with a significant (< 0.05) increase in the mean total area (per rat) enclosed by the lipopigment outlines. For both vitamin E deficiency and ageing this increase was associated with both an increase in the number of relatively large discrete lipopigment regions and a decrease in the number of relatively small discrete lipopigment regions. The findings in relation to vitamin E deficiency could be explained by an increased rate of lipopigment formation, involving processes which also occur in ageing.

Journal Article↗
PubMedDate not supplied

Synaptic mitochondria and ageing: computer-assisted morphometry in rat cerebellar glomeruli.

The ultrastructural features of synaptic mitochondria have been investigated by means of computer-assisted morphometry in the cerebellar glomeruli of young, adult and old rats. The volume fraction occupied by mitochondria (volume density: Vv), the number of organelles/ microm(3) (numerical density: Nv), the average volume (V) and the average length (Sk) of the mitochondria were the parameters measured in electron microscopic photos taken at an enlargement of x 8000. Vv showed a lifespan constancy. Nv was increased in the adult group vs. the young, but it was decreased in old animals as compared with the other 2 groups of age studied. V and Sk showed the same age-dependent changes: a significant decrease in the adults and a significant increase in the old rats vs. the other groups analysed, respectively. We interpret these findings to represent age-dependent morphofunctional adaptations occurring at synaptic mitochondria as a response to actual energy demands from the synaptic connectivity they subserve. Although impaired, the dynamic morphology of synaptic mitochondria appears to be capable of consistent compensative ultrastructural rearrangements in the central nervous system of old individuals.

Journal Article↗
PubMedDate not supplied

Morphometry of axon cytoskeleton at internodal regions of rat sciatic nerve during aging.

BACKGROUND: Nerve endings undergo a lifespan morphofunctional modulation which is reported to be markedly impaired with aging. Neurone structural remodelling is in charge of processes occurring in the nerve cell soma, however the axonal transportation of organelles and molecules by cytoskeletal elements plays a very important role in the morphological rearrangements taking place at peripheral compartments. OBJECTIVE: To assess the involvement of axonal ultrastructure in the reported age-related decline of slow axoplasm flow mechanisms, we carried out a morphometric study of axon cytoskeleton in aging. METHODS: Female Wistar rats (3, 12 and 30 months of age) were anesthetized and perfused with saline followed by a fixation solution (glutaraldehyde 5% + formalin 2% in 0.1 cacodylate buffer pH 7.4). The excised sciatic nerves were processed according to conventional electron microsopic procedures. Axons sectioned perpendicularly to their longitudinal axis at the internodal region (mean axoplasm area: 18.25-26.5 microm(2)) were sampled by a systematic random procedure. The overall number of neurofilaments (No.Nfs) and microtubules (No.Mts) per total axoplasm area analysed, the numeric density (number/microm(2) of axoplasm area) of neurofilaments (NaNfs) and microtubules (NaMts), the myelin thickness, the number of myelin lamellae and the R proportion [No. Nfs/(No.Nfs + No.Mts)] were the parameters measured by computer-assisted semiautomatic methods. RESULTS: No.Nfs, NaNfs, myelin thickness and the number of myelin lamellae did not change between 12 and 30 months of age, while a significant increase of these parameters was found in a comparison with younger rats. No.Mts and NaMts were significantly increased at 12 vs. 3 as well as at 30 vs. 12 months of age, respectively. R proportion did not show any difference due to age. CONCLUSIONS: The present findings support that the dynamic condition of the axonal cytoskeleton appears to be preserved at a high extent in aging. Thus, the intra-axonal defective spacing of cytoskeletal elements (e.g. neurofilaments), rather than their number, is proposed to contribute to the decline of the slow axonal transport of organelles and molecules reported in aging.

Actin Cytoskeleton↗
PubMedDate not supplied

The effect of vitamin E deficiency on the plasticity of cholinergic synapses: a computer-assisted morphometric study.

A computer-assisted morphometric study has been carried out on the ultrastructural features of the cholinergic synaptic junctional areas in the dentate gyrus supragranular layer of 11-month-old female Wistar rats and in littermates fed a vitamin E deficient diet for 10 months. The number of synapses/micro m(3) (numerical density: Nv), the average area of the junctional zones (S) and the total synaptic contact area/micro m(3) (surface density: Sv) were the three parameters taken into account. Nv and Sv significantly decreased, while S increased in the vitamin E deficient group. A size distribution of S showed that while in the normally fed animals the percentage of an enlarged synapses (0.16 micro m(2)>) accounts for 19% of the whole population, in the vitamin E deficient rats it raises at 44%. Relating the number of synapses to the number of dentate gyrus granule cells, the synapse-to-neurone ratio appeared to be decreased by 30% in the vitamin E deficient animals. It is currently reported that number (Nv) and size (S) of the synapses are in a close inverse relationship which aims at maintaining constant the total synaptic surface area (Sv) in a discrete volume of the neuropil, therefore, taken together per experimental group of rats, these parameters represent a reliable index of the synaptic morphological plasticity. Our present findings clearly document that the structural dynamics of the hippocampal cholinergic synapses are markedly affected by the absence of vitamin E from the diet and, in turn, support that an increased peroxidative stress may play a central role in the widely reported vulnerability of the cholinergic terminals with advancing age.

Acetylcholine↗
PubMedDate not supplied

Specificity of the zinc-iodide-osmium (ZIO) reagent in the nervous tissue: evaluation of the Ca++ binding sites hypothesis.

We tested the Ca(2+) binding sites detection hypothesis of the zinc-iodide-osmium (ZIO) staining on synaptic vesicles of rat cerebellar glomerulus using three different approaches based on the previous observation that Ca(2+) chelator EGTA can impede the staining reaction: (a) ZIO staining of "en bloc" tissue samples after EGTA exposure, (b) staining of ultrathin sections with ZIO reagent after EGTA treatment, (c) ZIO staining of isolated synaptic vesicles, preincubated in calcium ionophore A23187. The results of our investigation do not support the hypothesis. We conclude that ZIO staining can be referred to different molecules located mainly in secretory organelles.

Animals↗