Giovanna Sanna

Increasing Incidence of Multiple Sclerosis in the Province of Sassari, Northern Sardinia

Sardinia is a high-risk area for multiple sclerosis (MS), with prevalence rates of 150 per 100,000 population. The study included 689 MS patients (female-male ratio 2.6) with disease onset between 1965 and 1999 in the province of Sassari. The mean annual incidence rate increased significantly from 1.1 per 100,000 population in 1965–1969 to 5.8 in 1995–1999, with no significant difference for gender and province sub-areas. The mean age at onset increased significantly during the same period from 25.7 to 30.6 years, while the proportion of patients with progressive initial course declined over time. The marked increase of MS incidence and the change of MS clinical phenotype over time cannot be explained by ascertainment bias only, thus pointing to a corresponding change in the distribution of exogenous risk factors in this highly genetically stable population.

Epidemiology of Multiple Sclerosis in Northwestern Sardinia: Further Evidence for Higher Frequency in Sardinians Compared to Other Italians

The Sardinians are an ethnically homogeneous population, having a genetic structure quite different from that of all other Italian and European populations. All epidemiological studies carried out in Sardinia since 1975 indicate that this Mediterranean island shows twice the prevalence of multiple sclerosis (MS) compared to continental Italy, but the size of the Sardinian communities so far surveyed has been too small to draw definitive conclusions. To overcome this draw-back, we have studied the frequency of MS in a well-defined area of north-western Sardinia, with a population of about 270,000 in the 1991 census. Based on 276 MS cases, the prevalence on December 31st, 1991, was 102.6 per 100,000. The incidence, averaging 2 per 100,000 in the period of 1962 to 1971, rose to 5 in the period from 1977 to 1991. The present study confirms the higher frequency of MS among Sardinians compared to other Italian populations. Genetic, linguistic and historical data suggest a role of environmental and genetic factors in determining the notable difference in MS risk between Sardinia and the rest of Italy.

LRRK2 affects vesicle trafficking, neurotransmitter extracellular level and membrane receptor localization

The leucine-rich repeat kinase 2 (LRRK2) gene was found to play a role in the pathogenesis of both familial and sporadic Parkinson’s disease (PD). LRRK2 encodes a large multi-domain protein that is expressed in different tissues. To date, the physiological and pathological functions of LRRK2 are not clearly defined. In this study we have explored the role of LRRK2 in controlling vesicle trafficking in different cellular or animal models and using various readouts. In neuronal cells, the presence of LRRK2G2019S pathological mutant determines increased extracellular dopamine levels either under basal conditions or upon nicotine stimulation. Moreover, mutant LRRK2 affects the levels of dopamine receptor D1 on the membrane surface in neuronal cells or animal models. Ultrastructural analysis of PC12-derived cells expressing mutant LRRK2G2019S shows an altered intracellular vesicle distribution. Taken together, our results point to the key role of LRRK2 to control vesicle trafficking in neuronal cells.

Epidemiology of Myasthenia gravis in Northwestern Sardinia

A previous epidemiological study on myasthenia gravis (MG) in Sardinia indicated a prevalence rate of 4.5 per 100,000 population and an incidence of 0.25 per 100,000 population in the period 1958-1986. This study, however, investigated the entire Sardinian population (about 1,500,000) and the reported rates are likely to be underestimated. Because the use of a very large population has been found to cause major bias in case finding, the present study was designed to overcome this bias by determining the prevalence and incidence of MG in a well-defined area of Northwestern Sardinia, with a population of about 270,000 (1991 census). Potential MG cases were ascertained using all possible medical sources. The diagnosis of MG was based on the clinical, neurophysiological and conventional pharmacological findings (Tensilon test, response to anticholinesterases). On prevalence day (December 31, 1994) 29 MG patients were living in the study area (17 women and 12 men). Since the total population on prevalence day was 268,926 (137,284 women and 131,642 men), the calculated prevalence was 11.1 per 100,000 population (12.4 women and 9.9 men). The present study shows that the risk of MG in Sardinia is higher than previously suggested. The risk, however, is not significantly different from that found in other comparable Italian and European areas. It contrasts with what has been found for other autoimmune diseases such as multiple sclerosis and insulin-dependent diabetes mellitus in Sardinians, both showing frequencies up to 3-5 times higher than in the rest of Italy.

Bcl2-A1 interacts with pro-caspase-3: Implications for amyotrophic lateral sclerosis

Expression of mutant SOD1 typical of familial amyotrophic lateral sclerosis (ALS) induces the expression of Bcl2-A1, a member of the Bcl2 family of proteins, specifically in motor neurons of transgenic mice. In this work, we have used immortalized motor neurons (NSC-34) and transgenic mice expressing mutant SOD1 to unravel the molecular mechanisms and the biological meaning of this up-regulation. We report that up-regulation of Bcl2-A1 by mutant SOD1 is mediated by activation of the redox sensitive transcription factor AP1 and that Bcl2-A1 interacts with pro-caspase-3 via its C-terminal helix α9. Furthermore, Bcl2-A1 inhibits pro-caspase-3 activation in immortalized motor neurons expressing mutant SOD1 and thus induction of Bcl2-A1 in ALS mice represents a pro-survival strategy aimed at counteracting the toxic effects of mutant SOD1. These data provide significant new insights on how molecular signaling, driven by expression of the ALS-causative gene SOD1, affects regulation of apoptosis in motor neurons and thus may have implications for ALS therapy, where prevention of motor neuronal cell death is one of the major aims.

Effects of Some Yeast on Resveratrol Content During Alcoholic Fermentation

The variability of the content of four monomeric forms of resveratrol (3, 5,4’-trihydroxystilbene): trans and cis -resveratrol, , trans and cis -β-Dglucopyranoside in musts of Cagnulari grapes grown in northwest Sardinia, using different strains of the yeast Saccharomyces cerevisiae , was determined by HPLC at different stages of vinification. The first sample was taken after three days, the second 10 days after inoculation of the yeasts and the third after the samples had been stored for two months at 10°C. The data were elaborated by multivariate statistical analysis, considering the variability of the concentrations of the four stilbene forms at different times. The results showed that from the beginning of sampling the form of resveratrol present in the highest amounts was the glucosylated form, but this had already decreased significantly in the second sample. The decrease in the glucosylated forms was not, however, accompanied by a proportional increase in the free forms. In addition, some yeast strains were identified that do not substantially change the total content of the four monomeric forms of resveratol.

Content of Resveratrols as a Function of Red Wine Cultivar and of the Year Production (2000-2001-2002)

As a continuation of a previous research project, the variability of trans - and cis -resveratrol and their glucosides in red wines, from 14 different species of vine, was determined. The wine came from grapes grown on two plots of land at two separate locations differing in pedo-climatic conditions. The content of total resveratrol is between 1.55 and 16.76 mg/L with an average value of 6.71 mg/L. Moreover the results showed that trans - and cis -resveratrol are more correlated (r = 0.83) than trans - and cis -glucoside (r = 0.72), due to the uniformity of vinification treatments. The species of vine, having a higher mean content of total resveratrol, are: Refosco, Pinot Nero, Ciliegiolo, Montepulciano e Gaglioppo. The data, elaborated by multivariate statistical analyses (Principal Component Analysis and Discriminant Analysis), pointed out a good separation between the three vintages as a function of resveratrol content.