Biomedical subjects
S Algeri
Publications and source records attributed to S Algeri.
Lyophilized red wine administration prolongs survival in an animal model of amyotrophic lateral sclerosis.
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The effect of caloric restriction on the aortic tissue of aging rats.
Connective tissue shows peculiar and complex age-related modifications, which can be, at least in part, responsible for altered functions and increased susceptibility to diseases. Food restriction has long been known to prolong life in rodents, having antiaging effects on a variety of physiologic and pathologic processes. Therefore, the aorta has been investigated in rats fed normal or hypocaloric diet, from weaning to senescence. Compared with controls, caloric-restricted animals showed less pronounced age-dependent alterations such as elastic fiber degradation, collagen accumulation and cellular modifications. Immunocytochemical analyses revealed that elastic fibers were positively labelled for biglycan, decorin, ApoB100 (LDL), ApoA1 (HDL) and elastase and that the intensity of the reactions was time- and diet-dependent. With age, the major changes affecting aortic elastic fibers were increased positivity for decorin, LDL and elastase. Compared with age-matched normal fed rats, caloric restricted animals revealed lower content of LDL, decorin and elastase and higher positivity for HDL. These data suggest that a caloric restricted diet might influence the aging process of the arterial wall in rats, delaying the appearance of age-related degenerative features, such as structural alterations of cells and matrix and modified interactions of elastin with cells and with other extracellular matrix molecules.
Aging prolongs the stress-induced release of noradrenaline in rat hypothalamus.
A stress-induced increase in noradrenaline (NA) release was measured by intracerebral microdialysis in the hypothalamic paraventricular nucleus of freely moving Wistar-Kyoto rats at three different ages (6, 18 and 24 months). NA levels in 20-min dialysate samples were measured by high-performance liquid chromatography with electrochemical detection. Microdialysis sampling was done at the baseline during a 20-min immobilization stress and for the next 100 min. Basal NA release was not significantly different in the three age groups. The immobilization stress increased NA levels (247, 197 and 234% of the baseline for the 6-, 18- and 24-month animals, respectively) which was not significantly different in the three groups. In the two younger groups NA returned to the baseline in the first sample after the end of the stress (t = 40 min) whereas in the 24-month group it remained significantly higher for longer (until t = 60 min). Stress-induced release of hypothalamic NA thus appears to be prolonged in old rats.
Potential strategies against age-related brain deterioration. Dietary and pharmacological approaches.
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Effect of oxiracetam on scopolamine-induced amnesia in the rat in a spatial learning task.
The effects of the nootropic agent 4-hydroxy-2-oxopyrrolidinoacetamide (oxiracetam) on memory and performance impairments induced by scopolamine were evaluated in the Morris water maze task. No effect was seen on the performance of rats when treated with oxiracetam (30 mg/kg, IP) alone. Task performance of scopolamine (0.2 mg/kg, SC)-treated rats was impaired as compared to that of control animals. The behavioral deficits expressed in the task by scopolamine treatment were attenuated by the same dose of oxiracetam.
Correlation between electroencephalogram isoelectric time and hippocampal norepinephrine levels, measured by microdialysis, during ischemia in rats.
It is suggested that norepinephrine (NE) plays a role during transient forebrain ischemia. NE may have a protective action against neuronal cell death in the hippocampus, or it may be one of the causes of injurious ischemic effects. We used the microdialysis technique to study extracellular NE levels in the rat hippocampus before, during, and after 30 min of transient incomplete forebrain ischemia (induced by four-vessel occlusion) to describe the time course of NE in this condition. There was a maximal increase (fivefold) in extracellular NE after 10 min of reflow only when the electroencephalogram was isoelectric. NE levels returned to baseline 40 min after release of the carotid clamps and remained constant for the next 80 min. Thus there appears to be a transient NE overflow in the hippocampus during ischemia, closely related to the complete loss of brain electrical activity.
Effect of lifelong hypocaloric diet on discrete memory of the senescent rat.
The memory retention abilities of aged rats fed different diets were assessed in two different avoidance tasks. The standard passive avoidance procedure revealed an age-related memory impairment in old rats fed a standard diet (ST), whereas old rats fed a hypocaloric diet (HY) behaved similarly to young animals. To clarify whether this deficit could be attributed only to cognitive decay and not other factors, such as the tendency of old rats to prefer darkness to light more than young and adult animals, a multiple passive avoidance task was performed. This test offers rats the possibility to escape to a dark chamber in which they have never been shocked, and thus provides a means of checking factors other than memory retention abilities. All the old rats showed a more marked preference to escape to darkness compared to young and adult animals. However, senescent animals fed a ST diet had poor memory retention abilities compared to aged animals fed the HY diet, and young and adult rats. The results of this test confirmed the findings of the standard passive avoidance task.
The effect of caloric restriction on a rat model of aging: biological, pathological, biochemical and behavioral characterization.
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Previous experience facilitates preservation of spatial memory in the senescent rat.
In an attempt to evaluate whether previous training antagonizes age-related memory deficits, aged rats with previous training experience were compared with aged and young naive rats in the Morris water maze test. The findings of our study indicate that experience seems to facilitate the preservation of the spatial reference memory for 12 months in the aged rat, whereas senescent naive animals showed the usual age-related memory deficits. However, experience seems task-specific since the same aged rats fail to acquire a new different task.
Effect of Org2766, an ACTH(4-9) analogue, on recovery after bilateral transection of the fimbria fornix in the rat.
Facilitation of recovery after peripheral or central damage of the nervous system induced by neuropeptides was recently extensively reported. In a previous study we reported that Org2766, an ACTH(4-9) analogue, enhances recovery as assessed in a spatial orientation task after unilateral transection of the fimbria fornix in the rat. It was suggested that cross-lateral compensation by the intact fimbria fornix hippocampal system could account for the peptide-induced recovery. Therefore, the facilitatory effect of this neuropeptide was investigated in the present study after bilateral transection of the fimbria fornix. The present results indicate that Org2766 also attenuated the behavioral deficit of bilaterally transected animals in a spatial learning task, but does not affect behaviour of the lesioned animals in a passive avoidance test.
Org2766 improves performance of rats with unilateral lesions in the fimbria fornix in a spatial learning task.
ACTH and related peptides are known for their effects on behavior and for their efficacy on peripheral nerve regeneration. More recently, evidence demonstrating neurotrophic effects of Org2766 on recovery after damage of the central nervous system has become available. Aging studies indicated that particularly the hippocampus appears susceptible to peptide treatment. Therefore, in this study the neurotrophic influence of Org2766 on recovery of hippocampal functioning was studied after transection of the fimbria fornix connection. Analogous to results obtained with recovery of sensorimotor function following peripheral nerve damage a chronic treatment with Org2766 facilitates recovery of the impaired function, i.e. spatial learning in a Morris maze. However, the lesion-induced impairment of avoidance behavior was not influenced by the peptide treatment.
Behavioral and biochemical changes monitored in two inbred strains of mice during exploration of an unfamiliar environment.
Mice of the C57BL/6 (C57) and DBA/2 (DBA) strains were introduced individually in an unfamiliar environment (a large cage where food, water and sawdust had been removed). Over a 90-min period of observation, both strains presented a time-dependent decrease of locomotion and leaning and an increase of grooming. C57 mice were characterized by more cage cover climbing than DBA mice during the first 15-min stay in the new cage and by a significant decrease of this behavior after 90 min. During the first 60 min in the new environment, the DBA mice were less active than C57 mice, and both strains presented a significant increase of immobility after 90 min of test. After 30 min in the test situation, C57 presented a larger increase of plasma corticosterone levels than DBA mice. The plasma corticosterone levels were back to control values after 60 min of test in mice of the C57 strain and after 90 min in the DBA strain. Finally, both C57 and DBA mice presented a significant increase of homovanillic acid concentrations in the nucleus accumbens, but not in the striatum at 30, 60 and 90 min of testing. These results are discussed in terms of the possible involvement of mesolimbic dopaminergic system in mouse behavioral responses to an unfamiliar environment and of possible habituation to the stressful properties of this experience.
Miniaturized optoelectronic system for telemetry of in vivo voltammetric signals.
In vivo voltammetry is an electrochemical technique that uses carbon fiber microelectrodes stereotaxically implanted in brain areas to monitor monoamine metabolism and release continuously, in freely moving animals. Electric wires connect the polarograph to the animal. A wire-less transmission system (optoelectronic transmission, OPT) of voltammetric signals is described here. It uses infrared diffused light, exploiting the diffusion of the transmitted light over walls and ceiling towards a receiver. The transmission system consists of a main unit and a satellite unit (40 x 30 x 5 mm) positioned on the animal's back. Voltammetric recordings obtained by the classical system (with wires) and by OPT are well defined and almost identical in shape. The power supply is provided by two thin lithium batteries (+/- 3V) that can record for up to 20 h. OPT permits detailed behavioral observations since the animal can be left free to move in a spacious environment. Voltammetry using OPT allows simultaneous recording of neuronal firing activity as well as electroencephalographic recordings (EEG) since there is no cross-talk between the circuits used. The results illustrate the reliability and usefulness of this wire-less transmission system for studying relationships between neurochemical, behavioral and electrophysiological activities.
Effect of [D-Ala2,MePhe4,Gly-ol5]enkephalin and [D-Ala2,D-Leu5]enkephalin on ion and amino acid transport in rabbit ileum.
The selective mu-opioid agonist [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO) (10 microM) reduced the short circuit (Isc) and the L-valine induced increase of the transepithelial potential difference and Isc(delta Vms and delta Isc) measured in-vitro in rabbit ileum, with a mechanism antagonized by naloxone (1 microM). [D-Ala2,D-Leu5]enkephalin (DADLE) (10 microM) had no significant effect on the transepithelial potential difference (Vms), Isc, delta Vms and delta Isc. In the ileum deprived of the serosa and muscolaris, DAGO reduced the delta Vms and delta Isc, but not the Vms and Isc, suggesting localization of the receptors responsible for this latter effect in the myenteric plexus and/or the muscularis mucosae. These preliminary results suggest that in the rabbit ileum opioids influence electrolyte and amino acid transport and these effects may be at least partly mediated by mu-receptors.
Multiple and complex effects of buspirone on central dopaminergic system.
The effects of the anxiolytic drug buspirone and its metabolite 1-PP on the dopaminergic system were investigated. A single buspirone administration was found to decrease DA levels and increase its metabolite DOPAC in striatal samples. The levels of the other DA metabolite, 3MT, were unaffected; however its formation rate after inhibition of its metabolism, was found to be increased by buspirone. 1-PP did not affect either DOPAC or 3MT levels and formation. Striatal microdialysis showed that buspirone enhances DA release. In vivo voltammetry indicates that the increase of DA metabolism is identical in the two sampled dopaminergic areas, striatum and nucleus accumbens. On the basis of the results obtained ex vivo and in vivo the multiple effect of buspirone on dopaminergic system is discussed.
Aspartame and the rat brain monoaminergic system.
A high dose of aspartame (APM) was administered to rats to study possible effects on brain monoaminergic systems. APM and its metabolite phenylalanine (Phe) were given orally at doses of 1000 and 500 mg/kg, respectively. Significant increases were seen in brain Phe and tyrosine (Tyr) levels. Two different approaches were used to study monoaminergic systems: whole tissue measurements by HPLC-ED and in vivo voltammetry in freely moving rats. Dopamine, serotonin and their metabolites were taken as indexes of neuronal activity. In spite of the high dose used, no modification was found in monoamines or their metabolites in striatum, hippocampus and nucleus accumbens.
Peripheral effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its main metabolite 1-methyl-4-phenylpyridinium ion (MPP+) in the rat.
The effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its main metabolite 1-methyl-4-phenyl-pyridinium ion (MPP+) on catecholamine concentrations was tested in some peripheral organs of the rat. Acute injection of either compound caused a marked depletion of heart noradrenaline (NA). MPP+ had more effect than the parent compound. MPTP had no effect on adrenal catecholamines while its metabolite was effective, but only after several hours. Repeated MPTP and MPP+ injections (20 mg/kg X 5) resulted in marked depletion of heart NA and adrenal gland adrenaline. Clear recovery was observed in both organs 10 days after treatment.