Intracranial V. cholerae Sialidase Protects against Excitotoxic Neurodegeneration

Converging evidence shows that GD3 ganglioside is a critical effector in a number of apoptotic pathways, and GM1 ganglioside has neuroprotective and noötropic properties. Targeted deletion of GD3 synthase (GD3S) eliminates GD3 and increases GM1 levels. Primary neurons from GD3S−/− mice are resistant to neurotoxicity induced by amyloid-β or hyperhomocysteinemia, and when GD3S is eliminated in the APP/PSEN1 double-transgenic model of Alzheimer's disease the plaque-associated oxidative stress and inflammatory response are absent. To date, no small-molecule inhibitor of GD3S exists. In the present study we used sialidase from Vibrio cholerae (VCS) to produce a brain ganglioside profile that approximates that of GD3S deletion. VCS hydrolyzes GD1a and complex b-series gangliosides to GM1, and the apoptogenic GD3 is degraded. VCS was infused by osmotic minipump into the dorsal third ventricle in mice over a 4-week period. Sensorimotor behaviors, anxiety, and cognition were unaffected in VCS-treated mice. To determine whether VCS was neuroprotective in vivo, we injected kainic acid on the 25th day of infusion to induce status epilepticus. Kainic acid induced a robust lesion of the CA3 hippocampal subfield in aCSF-treated controls. In contrast, all hippocampal regions in VCS-treated mice were largely intact. VCS did not protect against seizures. These results demonstrate that strategic degradation of complex gangliosides and GD3 can be used to achieve neuroprotection without adversely affecting behavior

The modular systems biology approach to investigate the control of apoptosis in Alzheimer's disease neurodegeneration

Apoptosis is a programmed cell death that plays a critical role during the development of the nervous system and in many chronic neurodegenerative diseases, including Alzheimer's disease (AD). This pathology, characterized by a progressive degeneration of cholinergic function resulting in a remarkable cognitive decline, is the most common form of dementia with high social and economic impact. Current therapies of AD are only symptomatic, therefore the need to elucidate the mechanisms underlying the onset and progression of the disease is surely needed in order to develop effective pharmacological therapies. Because of its pivotal role in neuronal cell death, apoptosis has been considered one of the most appealing therapeutic targets, however, due to the complexity of the molecular mechanisms involving the various triggering events and the many signaling cascades leading to cell death, a comprehensive understanding of this process is still lacking. Modular systems biology is a very effective strategy in organizing information about complex biological processes and deriving modular and mathematical models that greatly simplify the identification of key steps of a given process. This review aims at describing the main steps underlying the strategy of modular systems biology and briefly summarizes how this approach has been successfully applied for cell cycle studies. Moreover, after giving an overview of the many molecular mechanisms underlying apoptosis in AD, we present both a modular and a molecular model of neuronal apoptosis that suggest new insights on neuroprotection for this disease

Esercizio fisico e salute nei diabetici di tipo 2. Una ricerca empirica sui costrutti di autoefficacia e concetto di Sé fisico

In the last years an increasing interest was manifested towards physical activity as tool to promote healthier lifestyles. Adults with diabetes are less prone to engage in regular exercise and when they adopt an active lifestyle are prone to disrupt it, before to gain some physical benefit or a psychological wellness. The present study analyses some useful predictors of exercise adherence as self efficacy and the physical self concept in a sample of 105 subjects with type 2 diabetes mellitus (62 men and 43 women; mean age 53.08 years). Previous experience in motor activities and usual barriers against motor practice were also taken into account. Results show that perceived self-efficacy and barriers against exercise are the best predictors of a regular motor activity; while body image discriminates only between females who practice or not a physical activity

Somatostatin- and Substance P-ergic neurons and Glial cell line-derived neurotrophic factor in the human archicortex

By means of immunohistochemistry, the localization of Somatostatin (SOM)- and Substance P (SP)-ergic neuronal populations was compared to the occurrence of Glial cell line-derived neurotrophic factor (GDNF) in the human hippocampus from prenatal to adult life stages. The results obtained i) confirm previous reports on the distribution of SOM and SP; ii) show that GDNF-like immunoreactivity occurs in an ample population of hippocampal neurons, with a main location in the pyramidal cells; iii) identify regions of codistribution of either neuropeptide with GDNF-positive elements. Although coexistence of GDNF with SOM or SP was not detected, the possibility that the trophic factor may act on the neuropeptide-containing neurons can be envisaged and is worth further analysis