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Aubert A.E.,The Interdisciplinary Center | Verheyden B.,The Interdisciplinary Center | D'Ydewalle C.,Laboratory of Neurobiology | Beckers F.,The Interdisciplinary Center | Van Den Bergh O.,Catholic University of Leuven
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2010

Sustained weightlessness affects all body functions, among these also cardiac autonomic control mechanisms. How this may influence neural response to central stimulation by a mental arithmetic task remains an open question. The hypothesis was tested that microgravity alters cardiovascular neural response to standardized cognitive load stimuli. Beat-to-beat heart rate, brachial blood pressure, and respiratory frequency were collected in five astronauts, taking part in three different short-duration (10 to 11 days) space missions to the International Space Station. Data recording was performed in supine position 1 mo before launch; at days 5 or 8 in space; and on days 1, 4, and 25 after landing. Heart rate variability (HRV) parameters were obtained in the frequency domain. Measurements were performed in the control condition for 10 min and during a 5-min mental arithmetic stress task, consisting of deducting 17 from a four-digit number, read by a colleague, and orally announcing the result. Our results show that over all sessions (pre-, in-, and postflight), mental stress induced an average increase in mean heart rate (Δ7 ± 1 beats/min; P = 0.03) and mean arterial pressure (Δ7 ± 1 mmHg; P = 0.006). A sympathetic excitation during mental stress was shown from HRV parameters: increase of low frequency expressed in normalized units (Δ8.3 ± 1.4; P = 0.004) and low frequency/high frequency (Δ1.6 ± 0.3; P = 0.001) and decrease of high frequency expressed in normalized units (Δ8.9 ± 1.4; P = 0.004). The total power was not influenced by mental stress. No effect of spaceflight was found on baseline heart rate, mean arterial pressure, and HRV parameters. No differences in response to mental stress were found between pre-, in-, and postflight. Our findings confirm that a mental arithmetic task in astronauts elicits sympathovagal shifts toward enhanced sympathetic modulation and reduced vagal modulation. However, these responses are not changed in space during microgravity or after spaceflight. Copyright © 2010 the American Physiological Society. Source

Herman W.A.,Outpatients Unit of Endocrine Diseases | Krzoska A.,Poznan University of Medical Sciences | Lacka K.,Metabolism and Internal Medicine | Bugaj R.,Laboratory of Neurobiology | Dorszewska J.,Laboratory of Neurobiology
Polski Merkuriusz Lekarski | Year: 2013

Metabolic syndrome (MS) is associated with low-grade systemic inflammation. Hyperhomocysteinemia is considered recently as a consequence of immune activation. Acute phase proteins, proinflammatory cytokines and probably homocysteine (hHcy) are involved in the pathogenesis of MS, atherosclerosis and ageing. The aim of our study was to investigate the reciprocal links between hHcy and selected negative and positive acute phase reactants as well as interleukin-18 in men over 40 years of age suffering from MS compared to healthy subjects. Material and methods. In 160 randomly selected men aged 40 to 70 years hHcy, C-reactive protein, transferrin, α1- antichymotrypsin and IL-18 were evaluated and features of MS using IDF (International Diabetes Federation-2005) criteria were estimated. Results. Hcy plasma levels are not correlated with age. Men suffering from MS revealed significantly higher serum hHcy levels than healthy subjects (11.52 ±6.87 μM/L vs 10.08 ±5.44 μM/L, p=0.0074). A weak but positive (r=0.099; p=0.014) correlation between hHcy and the numbers of MS traits is shown. However, the plasma hHcy level is correlated only with HDL-cholesterol serum levels (r= -0.132; p=0.035) and fasting blood glucose (r=0.164; p=0.009). hHcy concentration is strongly positively correlated with IL-18 (r=0.276; p=0.005), although not with CRP, α1-ACT and transferrin. Conclusions. In men over 40 years of age suffering from MS significant higher serum Hcy levels than healthy subjects are presented, but hHcy (as opposed to acute phase reactants) correlates only with IL-18 plasma concentrations. Source

Cole A.A.,Laboratory of Neurobiology | Dosemeci A.,Laboratory of Neurobiology | Reese T.S.,Laboratory of Neurobiology
Biochemical Journal | Year: 2010

Biochemical studies have suggested that certain synaptic proteins associate with lipid rafts to perform key functions within the synapse. However, variability in biochemical preparations raises questions as to which synaptic proteins actually associate with lipid rafts. In the present study, we use both electron microscopy and biochemistry to investigate AMPA (α-amino-3- hydroxy-5-methylisoxazole-4-propionic acid) receptor localization in synaptic membrane subfractions prepared in two different ways, by Triton X-100 detergent treatment or without detergent by sonication at high pH. Immunogold electron microscopy shows that a detergent-resistant synaptosomal membrane subfraction consists of empty vesicles 0.1-1.0 μm in diameter. A subpopulation of these vesicles labelled for glycosphingolipid GM1 ganglioside, a marker of lipid rafts, and 46%of the labelled vesicles also labelled for the AMPA receptor subunit GluR2. This co-segregation into specific vesicles does not depend on effects of detergent because a similar distribution of label was found in vesicles isolated without the use of detergent. Our results suggest that AMPA receptors localize within specific regions of synaptic membranes rich in G M1 ganglioside. © The Authors. Source

Gianni M.,Laboratory of Molecular Biology | Peviani M.,Laboratory of Neurobiology | Bruck N.,University of Strasbourg | Rambaldi A.,Ospedali Riuniti di Bergamo | And 6 more authors.
Leukemia | Year: 2012

All-trans retinoic acid (ATRA) is the only clinically useful differentiating agent, being used in the treatment of acute promyelocytic leukemia (APL). The use of ATRA in other types of acute myelogenous leukemia (AML) calls for the identification of novel strategies aimed at increasing its therapeutic activity. Here, we provide evidence that pharmacological inhibition of the mitogen-activated protein kinase, p38α, or silencing of the corresponding gene sensitizes APL and AML cell lines, as well as primary cultures of AML blasts to the anti-proliferative and cyto-differentiating activity of ATRA and synthetic retinoids. P38α inhibits ligand-dependent transactivation of the nuclear retinoic acid receptor, RARα, and the derived chimeric protein expressed in the majority of APL cases, PML-RARα. Inhibition is the consequence of ligand-independent binding of p38α, which results in stabilization of RARα and PML-RARα via blockade of their constitutive degradation by the proteasome. The inhibitory effect requires a catalytically active p38α and direct physical interaction with RARα and PML-RARα. Ser-369 in the E-region of RARα is essential for the binding of p38α and the ensuing functional effects on the activity of the receptor. © 2012 Macmillan Publishers Limited. Source

Gelosa P.,University of Milan | Mura E.,Laboratory of Neurobiology | Mauro A.,Laboratory of Neurobiology | Mauro A.,University of Turin | And 12 more authors.
Journal of Hypertension | Year: 2013

BACKGROUND AND OBJECTIVES: Spontaneously hypertensive stroke-prone rats (SHRSPs) develop hypertension, cerebrovascular abnormalities and a stroke phenotype in association with higher levels of proteinuria. Here, we focus on cerebral abnormalities preceding lesions detectable by MRI. METHODS: Longitudinal assessment of brain histology was performed in salt-loaded male SHRSPs (na=26) and Wistar-Kyoto (WKY) normotensive control animals (na=27). Groups of rats were sacrificed at different time points: Time 0, before the salt diet administration; Time 1, when proteinuria achieved 40mg/day; Time 2, when proteinuria exceeded 100mg/day. RESULTS: At Time 0, no brain lesions were observed. At Time 1, changes of the cortical penetrating arteries, vasogenic oedema, lacunae and focal cell loss appeared in SHRSPs and worsened at Time 2, although no lesions were yet detected by MRI. Staining for proliferation markers revealed a significant boost of cellular mitosis in the subventricular zone (SVZ) of SHRSPs. Moreover, we observed higher immunopositivity for nestin, glial fibrillary acidic protein and doublecortin (markers for neural stem cells, astrocytes and immature neurons, respectively). At Time 2, apoptotic caspase-3 as well as 4-hydroxynonenal-positive neurons were associated to decreased nestin and doublecortin staining. High expression levels of glial fibrillary acidic protein were maintained in the SVZ. No comparative alterations and SVZ activation were recorded in WKYs. CONCLUSION: Appearance of vascular changes in SHRSPs, before any MRI-detectable brain lesion, is coupled to active neural proliferation in the SVZ. With disease progression, only newborn astrocytes can survive, likely because of the neurotoxicity triggered by brain oedema and oxidative stress. © 2013 Wolters Kluwer Health / Lippincott Williams & Wilkins. Source

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