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P Fattoretti

Publications and source records attributed to P Fattoretti.

At least 19 recordsLinked to original sources
PubMed1998

Impaired succinic dehydrogenase activity of rat Purkinje cell mitochondria during aging.

The perikaryal Purkinje cell mitochondria positive to the copper ferrocyanide histochemical reaction for succinic dehydrogenase (SDH) have been investigated by means of semiautomatic morphometric methods in rats of 3, 12 and 24 months of age. The number of organelles/microm3 of Purkinje cell cytoplasm (Numeric density: Nv), the average mitochondrial volume (V) and the mitochondrial volume fraction (Volume density: Vv) were the ultrastructural parameters taken into account. Nv was significantly higher at 12 than at 3 and 24 months of age. V was significantly decreased at 12 and 24 months of age, but no difference was envisaged between adult and old rats. Vv was significantly decreased in old animals vs. the other age groups. In young and old rats, the percentage of organelles larger than 0.32 microm3 was 13.5 and 11%, respectively, while these enlarged mitochondria accounted for less than 1% in the adult group. Since SDH activity is of critical importance when energy demand is high, the marked decrease of Vv supports an impaired capacity of the old Purkinje cells to match actual energy supply at sustained transmission of the nervous impulse. However, the high percentage of enlarged organelles found in old rats may witness a morphofunctional compensatory response.

Aging↗
PubMed1996

Age-dependent decrease in the activity of succinic dehydrogenase in rat CA1 pyramidal cells: a quantitative cytochemical study.

A computer-assisted morphometric study has been carried out on the ultrastructure of perikaryal CA1 pyramidal cell mitochondria positive to the copper ferricyanide cytochemical reaction for succinic dehydrogenase (SDH) in rats of 3, 12 and 23 months of age. The cytoplasmic volume fraction occupied by the positive mitochondria (Volume density: Vv), the number of organelles/micron 3 of CA1 pyramidal cell cytoplasm (Numerical density: Nv) and the average mitochondrial volume (V) were automatically calculated by means of computer-assisted morphometry. Vv was significantly decreased in 23-month-old animals versus the other age groups. Nv was unchanged between 3 and 12 months of age, but was decreased to a significant extent in old animals. V did not undergo significant changes in the three age groups taken into account. In the old animals the percent of organelles smaller than 0.16 micron 3 is above 20%, while in the young and adult groups the same size of mitochondria accounts for 7 and 3%, respectively. Thus, a reduction in the number of medium sized organelles appears to be responsible for the decrease in Vv due to age. Since SDH activity is known to support maximum rates of respiration, quantitative estimation of the active mitochondria provides information on the metabolic competence of the cells investigated when energy demand is high. In this context, our present findings document that a significant impairment in the efficiency to match actual energy provisions occurs in old CA1 pyramidal cells.

Age Factors↗
PubMed1996

Neuronal plasticity in aging: a quantitative immunohistochemical study of GAP-43 distribution in discrete regions of the rat brain.

Age-related changes in neuroplasticity have been investigated considering the neuronal growth-associated protein GAP-43 as a marker of nerve cell structural adaptive capabilities. We carried out a quantitative immunohistochemical study on the distribution of GAP-43 in the molecular layer of the cerebellar cortex, in the inner molecular layer of the hippocampal dentate gyrus, in the stratum radiatum of the CA1 region, in layer 1 of the cingulate cortex and in the nerve fiber layer of the main olfactory bulb of 3-, 18- and 31-month-old Wistar rats. A decrease of GAP-43 immunoreactivity was observed in the old rats in comparison with the adult animals in all the 5 areas analyzed, although these variations were only statistically significant in the dentate gyrus, cingulate cortex and olfactory bulb. In these latter zones, GAP-43 immunolabeling is reduced by 54, 42 and 38%, respectively, in the old versus the adult group. Comparing these data with the age-dependent decrease of neuron density innervating the areas investigated, we support the hypothesis that the decline of GAP-43 observed in old animals documents a consistent reduction of axon plasticity in the inner molecular layer of the dentate gyrus and in layer 1 of the cingulate cortex. These results suggest an important role of GAP-43 as a marker of age-dependent deterioration of synaptic plasticity, especially in those areas of the brain involved in memory and emotional behavior.

Aging↗
PubMed1996

Synaptic structural dynamics and aging.

Synaptic junctional areas are not immutable structures, on the contrary, they are remodelled throughout the individual's lifespan as a consequence of environmental stimulations. This adaptive capacity of the synapses is discussed from a morphological standpoint with reference to aging. In old subjects, the number of contacts and the total surface area of synaptic appositions per unit volume of tissue decrease significantly, while the average synaptic size increases at a different extent according to the CNS area taken into account. This increase in synaptic average area is due to a higher percent of a subpopulation of enlarged contacts supposed to represent either the degenerating junctional zones or a compensatory phenomenon counteracting the synaptic reduction in number. Recent studies on perforated synapses support that the enlarged junctions are possible intermediates in synaptic physiological restructuring, thus the higher percentage of this type of contacts in the old CNS may witness unaccomplished synaptic turnover cycles. Taking into account the high metabolic rate of nerve cells, an age-related impairment in energy provision at synaptic terminal regions may constitute an early and subtle alteration affecting synaptic dynamic morphology in aging.

Aging↗
PubMed1996

Morphologic changes in cerebellar mitochondria during aging.

OBJECTIVE: To seek age-dependent morphofunctional changes in mitochondrial metabolic competence in the rat cerebellum. STUDY DESIGN: Three-, 12- and 24-month-old female Wistar rats were used for the present study. Each group consisted of five animals. The cytoplasmic fraction occupied by mitochondria (volume density, Vu), number of organelles per cubic micrometer (numerical density, Nu) and mitochondrial average volume (V) were measured in Purkinje cell perikaryal organelles histochemically stained to reveal succinic dehydrogenase activity in the three groups analyzed. RESULTS: Vu did not show significant differences due to age. Nu was constant between 3 and 12 months of age but decreased significantly in old rats. V did not show significant age-dependent differences. CONCLUSION: The present findings further extend the results of our previous studies on the ultrastructure of synaptic mitochondria and support the concept of marked metabolic impairment as a basal detrimental condition in the process of brain aging. As a marker of metabolically active mitochondria at high rates of cellular respiration, our present data document that with advancing age the number of efficient organelles decreases and that this may be of critical importance for the proper function of nerve cells when the energy demand is high.

Aging↗
PubMed1996

Deterioration threshold of synaptic morphology in aging and senile dementia of Alzheimer's type.

OBJECTIVE: To search for a deterioration threshold of synaptic ultrastructure in physiologic aging and senile dementia of Alzheimer's type (SDAT). STUDY DESIGN: The numerical density (Nu), average area (S) and surface density (Su) of the synaptic contact zones were investigated in the hippocampus and cerebellum from adults, elderly and SDAT patients by means of computer-assisted morphometry. RESULTS: The Nu and surface Su densities of the synapses decreased while the size of S enlarged in elderly and SDAT patients vs. the adults. By plotting Nu vs. S, the adult group showed a very high percentage of small junctions. In contrast, elderly and dementia patients demonstrated two overlapping populations of enlarged contacts. In SDAT the synapse-to-neuron ratio was decreased by 48% in the hippocampus and by 56% in the cerebellum. CONCLUSION: Our findings support the concept that the degeneration of synaptic contacts per se should be considered a crucial step in the progression of senile dementia, but the identification of a discrete deterioration threshold of synaptic morphology between aging and SDAT is not feasible at present.

Aged↗
PubMed1996

Acetylcarnitine modulation of the morphology of rat hippocampal synapses.

OBJECTIVE: To measure the effect of chronic administration of acetylcarnitine (ALCAR) on the morphologic plasticity of rat hippocampal synapses. STUDY DESIGN: Computer-assisted morphometry was carried out on the ultrastructure of hippocampal synapses in 6-, 12- and 22-month-old rats and in age-matched animals chronically treated with ALCAR from the age of 1 month up to when they were killed. Synaptic numeric (Nv) and surface (Sv) densities as well as the synaptic average area (S) were measured in the dentate gyrus supragranular layer. RESULTS: In control animals, Nv was constant between 6 and 12 months of age but significantly decreased in 22-month-old rats, S did not show significant differences due to age and Sv was unchanged between 6 and 12 months but decreased significantly in the old animals. In ALCAR-treated rats, Nv increased and S decreased significantly vs. age-matched controls. Sv showed lifespan constancy among the age groups analyzed. In ALCAR-treated rats the number of synapses smaller than 0.08 microns 2 increased by 18%, 9% and 10% at 6, 12 and 22 months of age, respectively. CONCLUSION: We interpret these findings to represent positive modulation of the synaptic structural dynamics in ALCAR-treated animals through improvements in energy provision at nerve terminals.

Acetylcarnitine↗
PubMed1995

Vitamin E deficiency as a model of precocious brain aging: assessment by X-ray microanalysis and morphometry.

Vitamin E (alpha-tocopherol) is a known biological antioxidant able to quench the lipid peroxidation chain and to protect the cellular structures (e.g., plasma membranes) from the attack of free radicals which are reported to play a primary role in aging. To assess whether the absence of alpha-tocopherol from the diet of young laboratory animals may be considered a reliable model of precocious brain aging, intracellular ionic content of brain cortex pyramidal cells, ultrastructural features of synaptic contact zones, synaptic mitochondria and perykarial mitochondria positive to the succinic dehydrogenase (SDH) histochemical reaction with copper ferrocyanide have been investigated by X-ray microanalysis and computer-assisted morphometry in young, adult, old and 11-month-old vitamin E deficient rats. Our data document significant alterations of intracellular ionic content, synaptic contact areas and synaptic and perykarial mitochondria in aging. Vitamin E deficiency caused similar alterations in adult animals. Taking into account the known role of alpha-tocopherol in protecting the cellular membrane structure, we support that the common process underlying the changes found in aging and vitamin E deficiency is an excessive deterioration of the neuronal membrane.

Aging↗
PubMed1994

Dynamic morphology of the synaptic junctional areas during aging: the effect of chronic acetyl-L-carnitine administration.

The ultrastructural features of hippocampal synaptic contact zones have been investigated by means of computer-assisted morphometry in rats of 6, 12 and 22 months of age and in age-matched animals chronically treated with ALCAR at a daily dose of 50 mg/100 g body weight from the age of 1 month up to the day of sacrifice. The number of synapses/microns 3 (Nv), the average size of the junctional areas (S) and the total area of the synaptic contact zones/microns 3 (Sv) were measured in tissue samples stained by means of the ethanol phosphotungstic acid (E-PTA) preferential technique for synaptic membranes. In control animals Nv was constant between 6 and 12 months of age, but significantly decreased in 22-month-old rats; S did not show significant differences due to age; Sv was unchanged between 6 and 12 months, but it decreased significantly in the old animals. In ALCAR treated rats Nv increased and S decreased significantly vs. Age-matched controls. Sv showed a lifespan constancy among the groups of age analysed. In ALCAR treated rats the number of contact areas smaller than 0.08 micron 2 increased by 18, 9 and 10% at 6, 12 and 22 months of age, respectively. ALCAR administration resulted in a lifespan modulation of synaptic structural dynamics. A proper metabolism at nerve terminals is accounted to play a crucial role in synaptic remodelling potential: on the basis of current research data, it is suggested that ALCAR may improve neuronal bioenergetic mechanisms.

Acetylcarnitine↗
PubMed1993

Morphological plasticity of synaptic mitochondria during aging.

A morphometric investigation has been carried out on the synaptic mitochondria of cerebellar glomeruli in young, adult and old rats by means of a computer-assisted image analysis technique. Mitochondrial volume density (Vv), numerical density (Nv), average volume (V) and average length (Skeleton = Sk) were investigated in tissue samples fixed, embedded and sectioned according to conventional electron microscopic methods. Vv was unchanged in the three groups of age taken into account. Nv was significantly increased in adult vs. young animals, whereas it was decreased in the old group as compared to both the other two groups investigated. V and Sk showed the same age-dependent changes: they significantly decreased in the adult vs. the young and the old groups of rats while increased significantly in the old rats vs. both the adult and young animals. A percentage distribution of Sk demonstrated that in the old group 20.6% of the population of synaptic mitochondria accounts for elongated organelles (> 5 microns) as compared to 8.6% and 5.3% in young and adult animals, respectively. The present findings match the changes previously reported by us on the ultrastructure of synaptic contact zones both in rats and human beings, and support the idea of an age-dependent dynamic adaptation in the morphology of synaptic mitochondria to cope with the metabolic needs of the pattern of synaptic connectivity they subserve.

Aging↗
PubMed1993

Ultrastructure of phosphotungstic acid (PTA) positive deposits in the hippocampus of senile demented patients.

To perform a quantitative investigation on synaptic ultrastructural features in the human hippocampus in normal old and senile demented patients we stained our tissue samples by means of the ethanol-phosphotungstic acid (E-PTA) preferential technique. In addition to the synaptic contact zones, we found that structures similar to neurofibrillary tangles (NFT) and senile plaques (SP) were remarkably positive to our staining procedure, while the background was faintly electron lucent. On the basis of the E-PTA staining properties and specificity, we support that the reactive sites of these positive structures are represented by basic amino acids. The recently demonstrated presence of 4 basic amino acids (1 arginine, 3 histidine) in the cleaved fragment of the amyloid precursor protein (APP) suggest us to hypothesise that this APP portion may represent the common constitutive element of the many morphologically different alterations found in the brains of senile demented patients.

Aged↗
PubMed1993

Compensatory enlargement of synaptic size in aging and senile dementia.

Synaptic contact zones in the dentate gyrus supragranular layer and cerebellar glomeruli of autoptic samples from adult, old and demented patients have been investigated by means of computer-assisted morphometric techniques. In physiological aging and senile dementia, the synaptic average area was significantly increased as compared with 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. In animal models, the enlarged contact zones are reported to 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 decrease in number and total contact area of the synaptic junctions.

Aged↗
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↗