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Stefano Govoni

Publications and source records attributed to Stefano Govoni.

25 records · Page 2Linked to original sources
PubMed2002

Selective impairment of p53-mediated cell death in fibroblasts from sporadic Alzheimer's disease patients.

In this study, we evaluated the response of different human skin fibroblast cultures obtained from eight probable Alzheimer's disease patients and eight non-Alzheimer's disease subjects to an acute oxidative injury elicited by H(2)O(2). This treatment generates reactive oxygen species, which are responsible for DNA damage and apoptosis. To compare the sensitivity of fibroblasts from Alzheimer's disease or non-Alzheimer's disease patients to H(2)O(2) exposure, we evaluated different parameters, including cell viability, the extension of DNA damage and the ability of the cells to arrest proliferation and to activate an apoptotic program. We found that fibroblasts from Alzheimer's disease patients were more resistant that those from control subjects to H(2)O(2) treatment, although the extent of DNA damage induced by the oxidative injury was similar in both experimental groups. The protective mechanism of Alzheimer's disease fibroblasts was related to an impairment of H(2)O(2)-induced cell cycle arrest and characterized by an accelerated re-entry into the cell cycle and a diminished induction of apoptosis. Fibroblasts from Alzheimer's disease patients also have a profound impairment in the H(2)O(2)-activated, p53-dependent pathway, which results in a lack of activation of p53 or p53-target genes, including p21, GADD45 and bax. This study demonstrates a specific alteration of an intracellular pathway involved in sensing and repairing DNA damage in peripheral cells from Alzheimer's disease patients.

Aged↗
PubMed2002

Ischemia-induced glutamate release in rat frontoparietal cortex after chronic alcohol and withdrawal.

High doses of ethanol increase stroke risk: in this context, a role for excitatory amino acids has been proposed. The present results show that, in frontoparietal cerebral cortex, chronic ethanol treatment (10% v/v in drinking water for 28 days) was able to slightly reduce glutamate release (evaluated through transdialysis coupled with high-pressure liquid chromatography) following focal ischemia as regards non-treated ischemic rats. This reduction was, however, not associated with decreased cerebral damage. In 24-h withdrawing rats, histological and morphometric analyzes showed an exacerbated cerebral damage coupled with higher glutamate and aspartate release compared to controls. These results suggest that adaptive changes following chronic ethanol consumption lead to an increased excitotoxicity that is particularly evident during the withdrawal condition.

Alcoholism↗
PubMed2002

Antiradical activity of water soluble components in common diet vegetables.

The antiradical activity of water-soluble components contained in mushrooms (Psalliota campestris), onions (Allium cepa), white cabbage (Brassica oleracea var. alba), and yellow bell peppers (Capsicum annuum) against hydroxyl radicals was tested in a chemical and biological system. The vegetable juices were obtained by centrifugation of a vegetable homogenate processed at 2 degrees C or heated at 102 degrees C. The chemical system consisted of a buffered reaction mixture composed of Fe(III)-EDTA, 2-deoxy-D-ribose, ascorbic acid, and H(2)O(2) generating the hydroxyl radical. The antiradical activity was expressed as an inhibition of deoxyribose degradation. The biological system consisted of IMR32 neuroblastoma cells exposed to H(2)O(2) in the presence or absence of the vegetable juices. Cells were pretreated for either 24 h or 1 h with the vegetable juices, and reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was used as a cell viability assay. All vegetable juices inhibited the degradation of deoxyribose and increased the viability of H(2)O(2) treated cells. Raw mushroom juice proved to be the most active in both cases. Boiling significantly affected the activity of mushroom juice, but did not change significantly the effect on onions and yellow bell peppers, and partially increased the activity of white cabbage juice. Mushroom antiradical activity was also confirmed by a cytofluorimetric analysis.

Agaricales↗
PubMed2002

In vivo dehydroepiandrosterone restores age-associated defects in the protein kinase C signal transduction pathway and related functional responses.

Elderly subjects are at increased risk of pneumonia, influenza, and tuberculosis. Besides the known age-related decrease in mechanisms for mechanical clearance of the lungs, impaired alveolar macrophage function contributes to the increased risk of illness in the elderly. We have previously shown that age-induced macrophage immunodeficiencies are associated with a defective system for anchoring protein kinase C. Castration of young male rats produces effects on alveolar macrophages similar to those of aging, suggesting a relationship between circulating sex hormones, particularly androgens, and the decreases in the receptor for activated C kinase (RACK-1) and macrophage function observed. The aging process in humans and rats is associated with a decline in the plasma concentrations of dehydroepiandrosterone (DHEA) and its sulfate, among other steroid hormones. We report here that in vitro and in vivo administration of DHEA to rats restores the age-decreased level of RACK-1 and the LPS-stimulated production of TNF-alpha in alveolar macrophages. DHEA in vivo also restores age-decreased spleen mitogenic responses and the level of RACK-1 expression. These findings suggest that the age-related loss in immunological responses, linked to defective pathways of signal transduction, are partially under hormonal control and can be restored by appropriate replacement therapy.

Aging↗
PubMedDate not supplied

The pharmacology of amyloid precursor protein processing.

The possibility to understand the causes and treat the symptoms of Alzheimer's disease patients is still a great challenge. The triggering events leading to the selective neurodegeneration observed in Alzheimer's brains are not completely understood. This lack of understanding of the pathophysiological processes posses an important theoretical challenge for the rational design of pharmacological intervention. The scientific community is divided over the pathogenesis of the disease which is historically divided between 'baptists' and 'tauists'. Baptists suggest that beta-amyloid, the peptide deposited in neuritic plaques, is the cause of all damages while tauists suggest that hyperphosphorylated tau, the cytoskeletal protein that forms neurofibrillary tangles, is the culprit for the disease. This review will be focused on the pharmacological modulation of the amyloid precursor protein metabolism, with the goal of reducing the formation of beta-amyloid. Over the years such an approach has led to the identification of a complex intracellular mechanism, which may be regulated by neurotransmitters and other ligands. More recently, these efforts have contributed to the characterization of the enzymes which regulate the formation of beta-amyloid.

Aged↗
PubMedDate not supplied

Effects of hormone therapy on brain morphology of healthy postmenopausal women: a Voxel-based morphometry study.

OBJECTIVE: Estrogens are known to be protective in age-associated cognitive changes in humans and in neurodegeneration in animal models. The aim of this study was to evaluate the potential effects of estrogen therapy (ET) on human gray matter volume in vivo. DESIGN: Forty healthy postmenopausal women underwent three-dimensional high-resolution magnetic resonance imaging: 17 were never treated, 16 were currently receiving ET, and 7 had had ET in the past. Voxel-based morphometry (VBM) with SPM2 was used, according to an optimized protocol, to compare women under past and current ET to those never treated. Significance threshold was set at P = 0.01, corrected by false discovery rate. RESULTS: Voxel-based morphometry indicated that estrogen use was associated with greater gray matter volumes in the whole group of treated women, which included the cerebellum (cluster size, Z coordinates: 5,527; 5.15; -14 -54 -10), the amygdaloid-hippocampal complex (left: 19; 3.55; -22 -4 -18; right: 45; 3.61; 16 -6 -16), and extended to the frontal, temporal, parietal, and occipital neocortex. The comparison current ET versus past ET use showed that women who underwent treatment in the past had greater volumes of gray matter compared to women under current treatment. CONCLUSIONS: ET might slow down age-related gray matter loss in postmenopausal women. The structures that exhibited greater volume in association with ET included the cerebellar and cerebral cortices and, typically involved in Alzheimer's disease, the medial temporal structures and the temporoparietal junction.

Aging↗