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Preconditioning (PC) is a phenomenon wherein a mild insult induces resistance to a later, severe injury. Although PC has been extensively studied in several neurological disorders, no studies have been performed in amyotrophic lateral sclerosis (ALS). Here we hypothesize that a sub-toxic acute exposure to the cycad neurotoxin beta-methylamino-L-alanine (L-BMAA) is able to delay ALS progression in SOD1 G93A mice and that NCX3, a membrane transporter able to handle the deregulation of ionic homeostasis occurring during ALS, takes part to this neuroprotective effect. Preconditioning effect was examined on disease onset and duration, motor functions, and motor neurons in terms of functional declines and severity of histological damage in male and female mice. Our findings demonstrate that a sub-toxic dose of L-BMAA works as preconditioning stimulus and is able to delay ALS onset and to prolong ALS mice survival. Interestingly, preconditioning prevented NCX3 downregulation in SOD1 G93A mice spinal cord, leading to an increased number of motor neurons associated to a reduced astrogliosis, and reduced the denervation of neuromuscular junctions observed in SOD1 G93A mice. These protective effects were mitigated in ncx3+/− mice. This study established for the first time an animal model of preconditioning in ALS and candidates NCX3 as a new therapeutic target.

BACKGROUND: Lemon processing procedures yield a significant amount of waste as peels, which are 57% of processed lemons and represent a possible source of bioactive compounds (essential oils, EOs). EOs were extracted from lemon fruits belonging to four cultivars harvested at four different sampling times (25 October, 23 November, 20 December, 1 February), characterized, and quantified through gas chromatography-mass spectrometry. RESULTS: The chemical composition of EOs highlighted that 26 compounds of the four lemon cultivars at the different ripening stages were clearly identified. The compounds analysed belonged to four chemical classes: monoterpene hydrocarbons, oxygenated monoterpenes, sesquiterpenes, and fatty alcohol esters. Among the monoterpene hydrocarbons, D-limonene,-pinene, and -terpinene were the most abundant; and among the oxygenated monoterpenes, -terpineol, nerol, and geraniol were the most abundant. Quantitative gas chromatography-mass spectrometry analysis of the most abundant monoterpene hydrocarbons ( -pinene, -pinene, myrcene, D-limonene, and -terpinene) highlighted that the amount of EOs decreased during ripening stages. 'Ovale di Sorrento' and 'Sfusato Amalfitano' showed the highest level of EOs in December, whereas in 'Femminello Cerza' and 'Femminello Adamo' this occurred in November. EOs, as well as the phenolic compounds, were positively correlated with the antioxidant activity (2,2 ′ -azino-bis(3-ethylbenzothiazoline-6-sulphonic acid). CONCLUSIONS: EOs reached the highest level in the four lemon cultivars at different ripening stages. Campanian cultivars ('Ovale di Sorrento' and 'Sfusato Amalfitano') showed the greatest EO content in November, whereas in Sicilian cultivars ('Femminello Cerza' and 'Femminello Adamo') this occurred in December. Besides phenolic compounds, measured in lemon peel extracts, EOs can contribute to antioxidant activity, as demonstrated by the positive correlation. Composition and quantification of EOs Chemical composition of EOs during ripening stagesThe chemical composition of extracted EOs was analysed during ripening stages (Table 2). A total of 26 compounds were clearly identified in the fruit peel extracts of the four cultivars and at different ripening stages. Significant variations among cultivars and ripening stages were observed.The compounds analysed were assigned to four chemical classes: monoterpene hydrocarbons, oxygenated monoterpenes, sesquiterpenes, and fatty alcohol esters. Monoterpene hydrocarbons were the dominant fraction of EOs, with an average relative abundance of 94.5%. During the ripening they decreased from 95.2% to 93.3%, and among them the compounds represented most were D-

In Italy, the relationship between income inequality and health is mixed and not universal, in so far as a positive association was observed only in provinces with lower absolute income. Elderly persons living in Southern Italy represent the population subgroup most vulnerable to unequal income distribution. Income inequality can, in part, explain the historically higher mortality among women in Southern Italy compared to women in the North. These results indicate that income inequality affects the health of population subgroups differentially.