Biomedical subjects

C Bertoni-Freddari

Publications and source records attributed to C Bertoni-Freddari.

82 records · Page 5Linked to original sources

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

Muscle involvement in rheumatoid arthritis: an ultrastructural study.

An electron microscopic investigation has been carried out on muscle bioptic samples from patients affected by rheumatoid arthritis (RA). This study was undertaken to seek further ultrastructural alterations affecting striated muscles in RA pathology. Bioptic samples were collected on a total of 30 surgical interventions of hip (10), knee (8), and foot (12). This yielded three muscle types: gluteus maximus, vastus lateralis, and extensor digitorum communis. Muscle samples from 12 patients with no RA stigmata, selected to match RA patients by age and gender, constituted the control group. Tissue samples were prepared both for conventional histochemical methods and according to conventional electron microscopic procedures, including morphometric analysis. Although to a different extent in each sample, in muscles from RA vs. controls the authors observed the simultaneous presence of discrete muscular alterations such as wider separation of myofibrils, myelin figures, dilated sarcotubular system, pleomorphic mitochondria, myofibril flaking, and lipofuscin deposition in the subsarcolemmal region. In addition to a progressive atrophy, the above findings are suggestive of rheumatoid myositis and lend further support to the still poorly documented presence of an idiopathic inflammatory myopathy and inclusion body myositis associated with RA.

Adult↗

PubMedDate not supplied

Mitochondrial genome lesions in the pathogenesis of sporadic Alzheimer's disease.

BACKGROUND: The recent, magnificent results of molecular biology concerning beta-amyloid (betaA) metabolism in early onset Alzheimer's disease (AD) have generated a series of new findings and, in turn, a new etiological concept. Attention on the early events in the pathogenesis of AD has been shifted from the chromosomal abnormalities in the nucleus of nerve cells onto genetic changes in the mitochondrial genome. This offers a new pathogenetic approach which also opens new pharmacological challenges particularly for the episodic forms of AD. OBJECTIVE: Alterations occurring at the mitochondrial genome result in major consequences of oxidative phosphorylation and, if a specific threshold is exceeded, they may constitute important causative events in the apoptosis of selected nerve cells. The fact that the main source of mitochondrial metabolism is its glucose turnover allows monitoring brain changes in glucose metabolism by 18F-2 deoxyglucose positron emission tomography. In the demented brain, a low glucose turnover causes a cholinergic deficit by decreasing the synthetic rate of acetyl coenzyme A (AcCoA). AcCoA represents the key substrate for the acetylation of choline to acetylcholine by choline acetyltransferase. The consistent energy need for AcCoA synthesis appears obvious when considering that 1 molecule of glucose generates just 2 molecules of AcCoA, but 38 molecules of ATP. In the brain, AcCoA is exclusively synthesized in the glycolitic pathway. Generation of betaA is increased if the synthetic rate of ATP drops below a critical threshold: under these conditions, the betaA precursor protein (betaAPP) is inserted only in part into synaptic membranes which have the highest betaAPP turnover. In conditions of short ATP supply, betaAPP is not split at the beta region by an ATP-activated protease and this results in a substantial increase in uncleaved betaA molecules. CONCLUSION: Peroxidative alterations in mitochondrial DNA are of importance in degenerative diseases of postmitotic tissues, particularly in degenerative diseases. This offers a new pharmacological approach for the treatment of AD. Neurotrophic factors and estrogen seem to be the first pharmacological leads.

Aging↗

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 significance of glucose turnover in the brain in the pathogenetic mechanisms of Alzheimer's disease.

This paper presents a comprehensive survey of the pathogenesis and pathophysiology of Alzheimer's disease (AD). Two mechanisms are of etiological importance in the development of a degenerative dementing brain disease: 1. Lesions in the mitochondrial genome that are caused by free radicals. Primary degenerative AD is characterized by a tendency to acquire random lesions within mitochondrial DNA that are produced by free radicals. The consequence of these lesions is a decrease in glucose turnover and a decline in oxidative phosphorylation. Point mutations on chromosome 21 are hypothesized to increase the susceptibility of mitochondrial DNA to lesions created by free radicals. 2. Ischemic brain lesions as well as traumatic brain damage cause an increase in the release of excitotoxic amino acids (glutamate, aspartate, etc.). These neurotransmitters increase CA(+2) influx into the nerve cell and significantly lower energy production. From a pathogenetic point of view, AD is characterized by a decrease in glucose turnover in the brain. The progression of AD can be monitored by F18- deoxyglucose PET studies. This technique also allows the recognition of patients who are prone to develop AD. The actual development of a cognitive deficit is a threshold phenomenon that occurs if glucose turnover in the hippocampus or temporoparietal cortex drops below a critical level of about 40% of the level of age-matched controls. The low glucose turnover in AD causes a cholinergic deficit by decreasing the synthesis of AcCoA, which is used by choline acetyltransferase in the acetylation of choline to acetylcholine. The decrease in glucose turnover also reduces oxidative phosphorylation. The resulting decrease in ATP triggers the hyperphosphorylation of tau protein by activating protein kinase 40erk. The hyperphosphorylation leads to the development of paired helical filaments. The generation of beta amyloid and the loss of neuronal synapses are also caused by a decrease in oxidative phosphorylation, since beta amyloid precursor proteins are not inserted into the membranes of nerve cells in the absence of a sufficient amount of ATP. This results in the generation of intact beta amyloid molecules and leads to amyloidosis in the brains of patients with Alzheimer's disease.

Aged↗

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↗