Age-related changes in brain deactivation but not in activation after motor learning.

It is poorly understood how healthy aging affects neural mechanisms underlying motor learning. We used blood-oxygen-level dependent (BOLD) contrasts to examine age-related changes in brain activation after acquisition and consolidation (24 h) of a visuomotor tracking skill. Additionally, structural magnetic resonance imaging and diffusion tensor imaging were used to examine age-related structural changes in the brain. Older adults had reduced gray matter volume (628 ±â€¯57 ml) and mean white matter anisotropy (0.18 ±â€¯0.03) compared with young adults (741 ±â€¯59 ml and 0.22 ±â€¯0.02, respectively). Although motor performance was 53% lower in older (n = 15, mean age 63.1 years) compared with young adults (n = 15, mean age 25.5 years), motor practice improved motor performance similarly in both age groups. While executing the task, older adults showed in general greater brain activation compared with young adults. BOLD activation decreased in parietal and occipital areas after skill acquisition but activation increased in these areas after consolidation in both age groups, indicating more efficient visuospatial processing immediately after skill acquisition. Changes in deactivation in specific areas were age-dependent after consolidating the motor skill into motor memory. Young adults showed greater deactivations from post-test to retention in parietal, occipital and temporal cortices, whereas older adults showed smaller deactivation in the frontal cortex. Since learning rate was similar between age groups, age-related changes in activation patterns may be interpreted as a compensatory mechanism for age-related structural decline.

Intermittent treatment with high dose nebulized beclomethasone for recurrent wheezing in infants due to upper respiratory tract infection.

BACKGROUND: To investigate if high dose inhaled beclomethasone dipropionate started early after upper respiratory tract infection (URTI) could reduce recurrent wheezing in infants. METHODS: Twenty-six ambulatory infants, 7-12 months of age, with recurrent wheezing during upper respiratory tract infection participated. All experienced at least three wheezing attacks. Those with underlying lung or systemic disease were excluded. Infants were divided into two groups in an open unblinded manner, until 13 patients had been recruited for each group. The groups were similar in risk factors for recurrent wheezing. Four treatment periods of 5 days were planned for group 1. The dose regimen was nebulized beclomethasone 400 mg by mask tid for 5 days. Treatment was started at the very first sign of URTI prior to any sign of wheezing. Group 2 did not receive any preventive treatment and constituted the control group. Symptoms scores were recorded. The number of emergency room visits, hospital admissions and short courses with oral steroids was also noted. RESULTS: Twelve infants completed 48 treatment periods. Five visited the emergency room, only one during beclomethasone therapy. Six received oral steroids, two receiving beclomethasone. No patient was admitted to the hospital. Symptom scores were significantly lower during beclomethasone treatment (p<0.05). No apparent adverse events were reported. CONCLUSIONS: The infant with recurrent wheezing during URTI is a therapeutic challenge. Most of these infants have prodromal symptoms for about 24 hours before wheezing starts. In the present study we observed favorable results, decrease in the number the child wheezed and the number of acute attacks, when high dose inhaled beclomethasone is administered during this critical time.

Radial maze performance and open-field behaviours in aged C57BL/6 mice: further evidence for preserved cognitive abilities during senescence.

C57BL/6 mice, aged 2 or 24 months, were tested in a radial maze and observed for an 8-min period, repeated on 3 consecutive days, in an open-field situation with a novel object. In the eight-arm maze, the number of unrepeated path choices made by old mice does not significantly increase with training, whereas it does in young mice. Older animals also take significantly longer to solve the task but the two age groups do not differ with respect to how many paths they run before making the first error or in the strategies used to solve the task. In the open-field situation, the two age groups differ with regard to grooming and rearing behaviour, while in the novelty situation, older animal show a higher level of locomotor activity, perform less freezing, and interact more with the novel object. Habituation curves for all parameters, except grooming in the open field, do not differ between the two groups, thus indicating that this form of nonassociative learning does not vary substantially with increasing age. Results are discussed in terms of preserved cognitive abilities during senescence in that strain.

Effects of oxotremorine on inhibitory avoidance behaviour in two inbred strains of mice: interaction with 5-methoxy-NN-dimethyltriptamine.

The effects of the cholinergic muscarinic agonist, oxotremorine (0.005, 0.01, 0.02 and 0.04 mg/kg), the serotonergic agonist, 5-methoxy-NN-dimethyltriptamine (5-MeODMT) (0.5, 1 and 2 mg/kg), and their combination, were investigated in C57BL/6 and DBA/2 mice using a one-trial inhibitory avoidance task, drug treatment being given immediately after the acquisition trial. Post-trial administration of oxotremorine facilitated, while post-trial administration of 5-MeODMT inhibited memory retention of both strains in a dose-dependent fashion. The DBA/2 strain was more affected by oxotremorine than the C57BL/6 mice; no strain-dependent sensitivity to serotonergic agonist administration was observed. In both strains, the combination of oxotremorine plus 5-MeODMT inhibited the performance improvement shown by the administration of the cholinergic agonist alone. The facilitatory role of cholinergic stimulation on retention performance was confirmed and an inhibitory action of the serotonergic system on memory processes was suggested. Moreover, the present results support a functional interaction between cholinergic and serotonergic systems on memory consolidation.

Genotype-dependent involvement of limbic areas in spatial learning and postlesion recovery.

Male C57BL/6 (C57) and DBA/2 (DBA) mice with hippocampal, amygdaloid, or sham lesions were tested in a radial eight-arm maze 1 or 4 weeks after surgery. The results show that the effect of the lesions varied according to the performance level of the strain considered. In the high-learner C57 strain, the two lesions impaired acquisition at both postlesion intervals. Conversely, in the low-learner DBA strain, only hippocampal lesions impaired acquisition 1 week but not 4 weeks after lesioning. It is hypothesized that if more limbic areas are involved in controlling spatial learning in C57 mice, these structures could be processing distinct but complementary memory attributes, thus contributing to a high baseline performance. This, however, also entails an increased sensitivity of C57 performance to brain damage with reduced possibilities of long-term recovery.

Serotonergic influence on cholinergic-induced analgesia: differences in two inbred strains of mice.

C57BL/6 (C57) and DBA/2 (DBA) inbred mice showed different analgesic responses to cholinergic stimulation. The simultaneous administration of muscarinic and serotonergic agonists, oxotremorine and 5-methoxy-NN-dimethyltryptamine (5-MeODMT), lowered the antinociceptive effect of the cholinergic drug in DBA mice, while no effects were detectable in the C57 strain. These results suggest a strain-dependent behavioural effect of the interaction of cholinergic and serotonergic neuronal systems.

Dose-dependent effect of GM1 ganglioside during development on inhibitory avoidance behaviour in mice: influence of the period of administration.

Groups of C57BL/6 mice were injected intraperitoneally with GM1 monosialoganglioside at different ages during development and subsequently tested for the retention of an inhibitory avoidance task 24 h after training. Results show improvements in inhibitory avoidance retention according to the age of the animals, the doses of GM1 used and the length of treatment. The effective doses ranged from 20 mg/kg for all age groups after 7 days treatment to 280 mg/kg for 6- and 7-week old animals after pre-trial treatment. Six- and 7-week-old mice are more sensitive to GM1 treatment than 5-week-old animals and, with decreasing lengths of treatment, increasing doses of GM1 are needed to improve the performance of the animals. These findings show that short treatment durations can be effective in improving inhibitory avoidance retention as long as the doses of GM1 administered are increased and that animals are more sensitive to the treatment when they are 6 or 7 weeks of age than when they are 5 weeks old.

Spatial learning in two inbred strains of mice: genotype-dependent effect of amygdaloid and hippocampal lesions.

Spatial learning performance and maze-running strategies were estimated in two inbred strains of mice, C57BL/6 and DBA/2, submitted to an 8-arm radial maze task. Subsequently the genotype-dependent effect of hippocampus and amygdala on the mastering of this task was examined as a function of the different acquisition model provided by each strain. The results firstly show that unoperated C57BL/6 mice reach a higher level of performance and develop a stronger preference for adjacent arms - 45 degrees angle - turns than unoperated DBA/2 mice. In the high learner C57BL/6 strain, both hippocampal and amygdaloid lesions impair performance and modify maze-running strategies. With practice, however, the difference between amygdala-lesioned mice and controls disappears while that between hippocampus-lesioned mice and controls persists. Conversely, in the low learner DBA/2 strain, hippocampal lesions have a negative effect on a single parameter of performance, while amygdaloid lesions only affect maze-running strategies. Taken together, these results confirm the specific control exerted by the hippocampus on spatial learning. Moreover, they suggest that the amygdala can parallel the role of the hippocampus as far as the baseline level of performance of the strain considered is high.

Open field behaviours and spatial learning performance in C57BL/6 mice: early stage effects of chronic GM1 ganglioside administration.

One month intact C57BL/6 mice were treated with GM1 ganglioside for 3 consecutive weeks. At 2 months of age, treated and control mice were observed in the open-field situation and tested for spatial learning in a radial eight-arm maze. The results showed that, in the open-field, treated mice displayed less freezing but more rearing behavior than control animals. In the radial maze, GM1-treated mice made more correct path choices before the first error within each trial than control mice. However, this improvement was limited to the first stage of training. These results suggest an early stimulating effect of the GM1 ganglioside treatment which could facilitate adaptive reactions to new situations.

Chronic administration of phosphatidylserine during ontogeny enhances subject-environment interactions and radial maze performance in C57BL/6 mice.

A longitudinal behavioral study was performed in mice exposed to the bovine brain phospholipid phosphatidylserine (BC-PS) from birth until sixty days. Examination of treated and control pups revealed no effect of the treatment on body weight nor on sensorimotor reflexes. At one and two months of age, when placed in an open field and, particularly, in the presence of a novel object, treated mice were found more interactive with their environment than control mice. Finally, when submitted to a radial eight-arm maze problem, choice accuracy was higher and maze-running strategies more adaptive in treated than in control adult mice. These results suggest a stimulating effect of the treatment on subject-environment interactions during ontogeny underlying improved cognitive abilities in adulthood.

[Gardner syndrome. A report of 3 cases in members of the same family]. / Sindrome di Gardner. Descrizione di tre casi componenti una stessa famiglia.

The aim of the present report is to describe the overall mandibular and extramandibular lesions correlated to Gardner's syndrome which were found in the same family (mother and two daughters). In two cases (mother and one daughter) mandibular lesions consisted of osteoma. In the latter, these were associated with composite odontoma. In the other daughter the lesions consisted of desmoid fibroma. The two daughters revealed single colonic polyposis whereas the mother was affected by multiple colonic polyposis and subcutaneous lipoma. Such a constellation of lesions may be attributed to Gardner's syndrome, a Mendelian hereditary syndrome which is often incomplete. In fact, intestinal polyposis can only be associated with one of the various extraintestinal manifestations of the syndrome. The recognition of the syndrome is important given the high percentage of intestinal polyp-adenocarcinoma associations.

Age-related cholinergic drug effects on analgesia in two inbred strains of mice.

The two inbred strains of mice C57BL/6 and DBA/2 are characterized by a different behavioral reactivity to cholinergic agents during development. The present experiment revealed that the strain-dependent differences in cholinergic-mediated analgesia during development disappeared during adult life. In fact, oxotremorine administration (0.0025 and 0.005 mg/kg) exerted the same analgesic effect in both strains at 6 months of age, in contrast with the finding of the lack of any effect of the drug in C57 mice at two months of age in comparison with DBA.

Effect of chronic GM1 ganglioside administration on passive avoidance retention in mice.

Chronic administration of GM1 ganglioside to C57BL/6 mice during development improved passive avoidance retention. A significant weight increase was also evident in the treated animals in comparison with the control group. The results are discussed in terms of the possible effects exerted by GM1 upon the cholinergic mechanisms of this inbred strain.

Developmental differences of antinociceptive effects of oxotremorine in two inbred strains of mice.

During development the C57BL/6 and DBA/2 mouse strains present morphological variations in cholinergic forebrain structures correlated with different behavioral reactivities to cholinergic agents. The present research assessed that these strain-dependent differences are also present in cholinergic-mediated analgesia. The administration of oxotremorine (0.0025, 0.005 and 0.01 mg/kg) to 30- and 60-day-old C57 and DBA mice resulted in dose- age- and strain-dependent analgesia. In particular oxotremorine is more effective in DBA/2 than in C57BL/6 mice and the latter strain showed a significant decrease of analgesic response in adulthood.

Phosphatidylserine administration during postnatal development improves memory in adult mice.

Postnatal administration of an aqueous suspension of phosphatidylserine (BC-PS) to C57BL/6 mice resulted in improvement of memory processes in adulthood, as assessed in a passive avoidance task. These findings are discussed in terms of the effects of BC-PS on cholinergic mechanisms and of cholinergic patterns of this inbred strain.

The first agonist and antagonist burst in patients with an upper motor neuron syndrome.

Rapid elbow flexion movements were studied in patients with an upper motor neuron syndrome following a stroke. The velocity of movements was slower than normal. The initial bursts of electromyographic (EMG) activity in both the agonist and antagonist muscles were prolonged. As in normal subjects, the first agonist burst increased in duration with larger movements, but it generally remained about 40 ms longer than normal. The size of the first agonist burst also increased with larger movements. A fixed linkage between burst duration and level of motor unit recruitment, together with a deficient corticospinal command, could explain the prolonged burst duration with preserved ability to modulate the burst.

Distribution of two aminotransferases and D-amino acid oxidase within the nephron of young and adult rats.

In the adult rat kidney, alanine aminotransferase (EC 2.6.1.2), aspartate aminotransferase (EC 2.6.1.1) and D-amino acid oxidase (EC 1.4.3.3) were measured in glomeruli, 4 parts of the proximal tubule, 2 parts of the distal tubule and in patches from the thin limb area and the papilla. These enzymes were measured in more limited parts of the nephron during postnatal development. Adult aspartate aminotransferase activities (percentage of the highest) ranged from 100 in the distal straight segment to 25 in the late part of the proximal straight segment to 10 in the thin limb and papillary area. Alanine aminotransferase (lower by a factor of 100 in absolute terms) was distributed as the mirror image of aspartate aminotransferase within proximal and distal tubules. D-Amino acid oxidase was 850-fold higher in proximal straight segments than in medullary structures. During development alanine aminotransferase increased 6-fold and D-amino acid oxidase, 4.5-fold in proximal straight tubules but aspartate aminotransferase increased in distal straight tubles 8-fold.

Distribution along the rat nephron of three enzymes of gluconeogenesis in acidosis and starvation.

Methods were devised or modified which made it possible to measure phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase in seven defined parts of single nephrons and in patches from thin limb and papilla areas dissected from freeze-dried microtome sections of rat kidney. All three enzymes were essentially confined to the proximal tubule. In normal kidneys, the levels were highest in the proximal convoluted tubule. Glucose-6-phosphatase was 20 times higher in the early part of the convoluted segment than in the late part of the straight segment. With one exception, in acidosis, only phosphoenolpyruvate carboxykinase increased (fourfold in the proximal convoluted segment but much less in the straight portion). In starvation, phosphoenolpyruvate carboxykinase increased about as much as in acidosis in the proximal straight tubule, but not as much in convoluted portions, whereas glucose-6-phosphatase rose modestly in both parts of the proximal tubule and fructose bisphosphatase rose only in the straight tubule, especially the early segment. It is suggested that ammoniagenesis can accompany gluconeogenesis in the proximal convoluted tubule but not in the straight segment.

Gluconeogenic enzymes in defined structures of developing rat nephron.

Three gluconeogenic enzymes, P-pyruvate carboxykinase (PPCK), fructose-1-6 bisphosphatase (FBPase), and glucose-6-phosphatase (G6Pase) were measured in identified structures of rat nephron from 2 days before birth to maturity. In the proximal convoluted tubule, the three enzymes increased from the earliest age assayed to +14 days (PPCK, 7-fold, FBPase, 2-fold and G6Pase, 50-fold). Among the 7 defined structures that were analyzed, highest levels at all ages were in the proximal convoluted tubule with almost no activity in the distal convoluted tubule. All three enzymes had negligible activity in the neogenic zone and mesenchyme. Supported by grants from the Public Health Service (HD 03891 and NS-05221) and the American Cancer Society (P-78).