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S Algeri

Publications and source records attributed to S Algeri.

102 records · Page 6Linked to original sources

Age-related changes in metabolic responses to chronic monoamine depletion in central dopaminergic and serotonergic systems of rats treated with reserpine.

Groups of 5, 15, and 27-month-old rats were treated with reserpine (5 mg/kg IP) and killed after 1, 7, 14, and 21 days. Reserpine's effects on dopamine (DA) and serotonin (5HT) metabolism were studied in the striata and limbic areas, on the basis of changes in metabolite concentrations and a calculated index [delta(C/M)] expressing changes in the molar ratio between metabolite and parent monoamine. Twenty-four hours after drug treatment, when the two monoamines reached a new steady-state, about 10% of the normal concentration, there was evident enhancement in the metabolism of striatal DA, indicated by HVA levels and delta(C/M) changes. This increase was significantly lower in the senescent rats. In contrast with HVA, the levels of DOPAC were lowered in reserpinized rats. This effect, present in all three age groups, lasted up to 21 days in young and 14 days in adult and old rats. However, for this metabolite too, the delta(C/M) indicated an increase in its formation which was lower in 27-month-old rats. Similar effects were observed in limbic areas, but here the age-related differences were less evident. Serotonin metabolism was also increased by reserpine as indicated by the delta(C/M). This parameter was lower in young than in adult and old rats, at least in limbic area. Similarly, 5HIAA increased only in the senescent rats. These age-related differences were not evident in striata. In this rat population, aging apparently modified the compensatory metabolic responses of some dopaminergic and serotonergic systems. The direction of these changes, however, depends on the system and the brain region considered.

3,4-Dihydroxyphenylacetic Acid↗

Effect of life-long hypocaloric diet on age-related changes in motor and cognitive behavior in a rat population.

Aged (24 months), adult (12 months), and young (4 months) rats kept on standard or hypocaloric diets from the age of three weeks old were tested in a range of behavioral tests to determine the effects of aging on sensory-motor and cognitive behavior and to assess whether such effects were prevented by life-long calorie restriction. An age-related deterioration of sensory-motor functions, motility and exploratory activity was observed in all the senescent animals independent of diet. Swimming ability did not deteriorate with age. Spatial memory, evaluated by the Morris water maze test, showed some deterioration in normally fed adult rats as indicated by the deceleration in the learning curve. In aged rats, not only was learning slowed down, but memory utilization was also impaired. These cognitive deficiencies were absent in rats fed the hypocaloric diet.

Aging↗

Age-related ability of rats kept on a life-long hypocaloric diet in a spatial memory test. Longitudinal observations.

Cognitive behavior was assessed in a test specific for spatial memory, according to a longitudinal experimental model, in populations of 12-, 24- and 30-month-old rats which were fed ad lib either a standard (ST) or a hypocaloric (HY) diet, that had been shown to reduce age-related pathologies and to increase survival. Already at 12 months of age, some cognitive deficits were observed in ST but not in HY rats. When retested 12 and 18 months later, the animals performed better at the beginning of the test than when tested for the first time, indicating that some aspects of previous experience lead to a preservation of spatial memory. Deficits which had been previously observed in 2-year-old groups in a cross-sectional experimental model were not evident this time. Some of the differences between the two diet groups observed 12 months before disappeared. When testing was repeated for the third time at 30 months of age, ST fed rats presented very marked deficits in learning and in memory, which were not seen in the HY group. It thus appears that a dietary regimen in which part of the calorie-rich components, such as lipids and carbohydrates, are replaced with vegetable fibers, retards some of the age-related deteriorations of brain functions.

Aging↗

Aging and food restriction: effect on lipids of cerebral cortex.

In experimental animals dietary restriction reduces the body weight increase due to aging, increases longevity and delays the onset of age-related physiological deterioration, including age-related changes in serum lipids. Little is known about the influence of food restriction on brain lipids, whose concentration and composition have been shown to change with age. We studied whether some biochemical and biophysical parameters of rat brain membranes, known to be modified with age, were affected by a diet low in calories, in which 50% of lipids and 35% of carbohydrates have been replaced by fibers. The diet was started at weaning and maintained throughout the animal's entire life span. Animals fed the low calorie diet survived longer and gained less body weight than standard diet fed rats. Age-related increases in microviscosity, cholesterol/phospholipid and sphingomyelin/phosphatidylcholine ratios were reduced or restored to the levels of young animals in cortex membranes of 32 old rats fed the low calorie diet, while the age-related increase in mono- to polyunsaturated fatty acid ratios in phospholipids was further raised. In conclusion we have shown that a diet low in calories and high in fibers affects lipid composition in the rat brain, in a direction opposite to that normally believed to reduce age-related deterioration of brain functions.

Aging↗

Deterioration of spatial and nonspatial reference and working memory in aged rats: protective effect of life-long calorie restriction.

Two different aspects of learning (spatial and nonspatial) and two different types of memory (reference and working) were simultaneously measured in populations of 3- (young), 11- (adult), and 25-month-old (aged) rats fed ad libitum either a standard (ST) or a hypocaloric (HY) diet. All groups, regardless of age or diet, showed ability in learning all four versions of the task. However, old ST rats were significantly slower and less efficient at learning than the young and adult ST rats. In contrast, senescent HY rats' cognitive abilities did not differ from those of their young and adult counterparts. The decline in reference and working memory in the aged ST rats was more pronounced in the spatial than the nonspatial version of the task. This study confirms and extends to more specific aspects of memory our earlier finding that age-related cognitive deterioration in rats was antagonized by life-long calorie restriction.

Aging↗

A reduced calorie-high fiber diet retards age-associated decreases in muscarinic receptor sensitivity.

The effects of a reduced calorie-high fiber diet (RCHF) were examined on three cholinergic signal transduction (ST) parameters: (a) oxotremorine enhancement of K(+)-evoked dopamine release and (b) carbachol-stimulated low KM GTPase activity [an indicator of muscarinic receptor (mAChR)-G protein coupling/uncoupling], and (c) [3H]Quinuclidinyl benzilate (QNB) autoradiography. Comparisons were made among: young control (6 months), old normal control, old reduced calorie high fiber [both 24 months)]. The results indicated that old reduced calorie high fiber rats (1900 kcal/kg/day, 2.4%, lipids 2.4%, fiber 28%, carbohydrates 40.7%) as compared to the old normal control rats (3000 kcal/kg/day, 4.8% lipids, 4.2% fiber, carbohydrates 61.5%) showed a retardation of age-related deficits in dopamine release (a above) and GTPase activity (b above). These parameters were 25% higher in the old reduced calorie high fiber rats as compared to old normal controls and did not differ from young controls, even though there was no increase in mAChR concentration in the restricted group. Thus, these results indicate that a reduced calorie high fiber diet as utilized in these experiments was effective in retarding the age-related decrements in two of three signal transduction parameters. They are discussed in terms of the induction of membrane changes (e.g., fluidity) or related decreases in oxidative stress by the restricted diet that may be involved in these signal transduction effects.

Aging↗

Differential response to immobilization stress of striatal dopaminergic and hippocampal noradrenergic systems in aged rats.

The effect of restraint stress on synthesis of central norepinephrine (NE) and dopamine (DA) was studied in adult and old rats. The rate of in vivo synthesis of the two catecholamines was determined in hippocampus (a prevalently noradrenergic area) and in striatum (a prevalently dopaminergic area) by measuring the accumulation of DOPA for 60 min after decarboxylase inhibition. NE synthesis was stimulated by stress in the first 30 min, after which the accumulation of DOPA declined. The stimulation was much greater in old rats. In striatum, endogenous DOPA concentration was significantly lower in old rats. Stress significantly enhanced DOPA accumulation in the first 30 min in both age groups but after this interval accumulation continued linearly only in young rats. These results indicate that in aged rats the response to stress of some noradrenergic and dopaminergic systems may be altered in opposite directions.

Aging↗

Subunit and region-specific decreases in nicotinic acetylcholine receptor mRNA in the aged rat brain.

We have investigated possible changes in the mRNA levels for several alpha and beta subunits of the nicotinic acetylcholine receptor (nAChR) and the level of binding for nicotinic ligands in 7- to 32-month-old rats. Alpha4 and beta2, and to a lesser extent alpha6 and beta3, mRNA levels showed decreases between 20 and 30% at 29 months of age which in some areas reached 50% at 32 months of age. Alpha7 showed a small increase from 7 to 14 months and then a progressive decrease from 14 to 32 months down to the 7-month levels. 3H-epibatidine binding did not significantly change from 7 to 32 months of age in rat tel- and diencephalon. Binding in the substantia nigra was exceptional in that it showed a significant decrease starting from 23 months of age. 125I-alpha-bungarotoxin binding showed a pattern of change which roughly paralleled that of alpha7 mRNA. These findings show that an alteration in some steps of nAChR biosynthesis takes place during aging, which may be related to functional changes in nicotinic transmission.

Aging↗

Nutritional antioxidants as antidegenerative agents.

In this study, primary cultures of cerebellar granule neurons were prepared from eight-day-old Wistar rats, and maintained in an appropriate medium containing a high (25 mM) concentration of KCl. All experiments were performed with fully differentiated neurons (eight days). To induce apoptosis, culture medium was replaced with a serum-free medium (containing 5 mM KCl) eight days after plating. In another series of experiments, apoptosis was induced by application of glutamate (50 microM) to the cell cultures. Apoptosis was measured by flow cytometry, the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick end-labeling) method, and by the classical method of DNA fragmentation. Since there is evidence that an increased formation of reactive oxygen species (ROS) is involved in the apoptosis induced by both low K(+) concentrations and glutamate, a series of natural antioxidants and a red wine lyophilized extract (which is rich in antioxidant compounds) were tested in our experimental model. It was found that ascorbic acid (30 microM) and a red wine lyophilized extract (5 microgram/ml) were capable of blocking the apoptotic process. Addition of the following natural antioxidants did not have any protective effect on apoptosis induced by low K(+) concentrations: trans- and cis-resveratrol (5-200 microM), alpha-tocopherol (100-200 microM), reduced glutathione (100-400 microM), 3-hydroxytirosol (25-100 microM), epicatechin (25-100 microM), or quercetin (25-50 miroM). It is concluded that only a limited number of natural antioxidants are provided with antiapoptotic activity in cultured cerebellar granule neurons. This effect is probably exerted by reducing ROS formation, and by blocking caspase-3 activity.

Animal Nutritional Physiological Phenomena↗