77 research outputs found
Effect of Electrolyzed Reduced Water in an Animal Model of Parkinson-Like Disease
No full textEffect of Electrolyzed Reduced Water in an Animal Model of
Parkinson-Like Disease
Cinzia Nasuti1, Donatella Fedeli1, Laura Bordoni2, Maura Montani3,
Ivan Dus4, Rosita Gabbianelli1
1School of Pharmacy, University of Camerino, Italy; 2School of Advanced
Studies, University of Camerino, Italy; 3School of Biosciences and
Veterinary Medicine, University of Camerino, Italy; 4Head of Research for
Chanson Water Company Taiwan
Objectives: Early life environmental factors, life style and diet have a
profound impact on the organism’s later development and subsequent onset of
age-related diseases such as neurodegenerative diseases. In previous studies, we
developed an animal model where the early life exposure (from postnatal day 6
to 21) to low dose of pesticide permethrin (PERM, 34 mg/kg) induced Parkinsonlike
neurodegeneration in rats characterized by decreased dopamine, Nurr1 and
glutathione levels in the basal ganglia, altered immune responses and gut
disbiosis. The animal model was exposed to a neurotoxin PERM that is an insecticide
widely used for indoor and outdoor applications (i.e. carpets, kitchen
worktops other treated wood furniture, lawn, mosquito control). The presence
of its metabolites in the urine of 98% of population makes this insecticide a
reliable environmental risk factor to health.
The present study aims to test the effect of electrolyzed reduced water
(ERW) on this animal model developing neurodegenerative disease after
exposure to PERM pesticide in neonatal age.
Methods: The effect of ERW is determined by cognitive tests, dopamine and
Nurr1 levels measured in basal ganglia and Tyrosine Hydroxylase (TH) immunostaining
in the Substantia Nigra pars compacta (SNc) in 60-day-old rats.
Results: When working memory is assessed in a T-maze, PERM group has a
worst performance compared with healthy controls, whereas the performance
of PERM+ERW is similar to control group. The same trend is observed for the
average of perseverative errors.
With regard to dopamine levels measured by HPLC in basal ganglia,
decreased levels are observed in PERM group compared to control group,
whereas the co-treatment with PERM+ERW protects against the damage induced
by the pesticide even increasing the levels of dopamine. Similar results are
obtained with regard to Nurr1 levels measured by western blot in basal ganglia.
Immunohistochemical analysis with anti-TH antibody marking dopamine
neurons in SNc shows a reduced number of TH-positive neurons in PERM rats
compared to control rats, whereas a slight increase (not statistically significant)
was observed in the PERM+ERW group with respect to PERM group.
Conclusion: The use of ERW as functional water could be helpful as a therapeutic
tool in the prevention of neurodegenerative diseases
Early life permethrin treatment induces in striatum of older rats changes in alpha-synuclein content
No full textObjectives: Many reports have demonstrated the strong relationship between environmental exposure during the first stages of life and the development in adult phase of neurodegenerative disorders. Previous studies performed in rats exposed from postnatal day 6 to 21 to low dose of permethrin (PERM) induced Parkinson-like neurodegeneration characterized in the striatum by a decrease of Nurr1 gene and protein expression, reduced dopamine level, together with its accelerated turnover (1-3). α-Synuclein is a presynaptic neuronal protein that contributes to Parkinson pathogenesis through its aggregation in oligomeric conformations called protofibrils that mediate disruption of cellular homeostasis and neuronal death. The present work aims to analyze in the striatum of early PERM treated rats the -sinuclein content in the adolescent, adult and old rats.
Methods PERM was dissolved in corn oil and administered orally to Wistar rats for 15 days, once a day in the morning from PND6 to PND21. Control rats were treated with vehicle (corn oil 4 ml/kg) on a similar schedule. Rats were sacrificed after 90 days (adolescent age), 180 days (adult age) and 300 days (old age) from the treatment and the striatum collected and kept at -80°C. Tissue lysates were prepared using two different buffers that solubilize -sinuclein in the free and aggregated forms. 40 g of protein were used for western blot analysis, separated using SDS–PAGE (7,5%) and electrophoretically blotted on a nitrocellulose support (Hybond C, Amersham Bioscience, Little Chalfont, UK). -synuclein antibody was purchased by Santa Cruz.
Results -synuclein free resulted more expressed in striatum from adolescent treated rats with respect to control while in samples from adult and old rats we observed an opposite situation with decreased level of -sinuclein in treated respect to their controls. Different oligomeric conformations of the protein were also observed when we analyzed by western blotting the lysate with solubilised aggregated protein. Striatum from adolescent treated rats shows higher expression of protein respect to the control with the formations of oligomers
Conclusions The early life treatment with PERM induces more significant effect on adolescent rats with the increase of -synuclein in both form, free and aggregated. This behavior could be explained with a more effective impairment of dopaminergic system in the first important phase of the life such as adolescence.
References:
1) Carloni M et al. 2012, Exp Gerontol. 47(1):60-66 2) Nasuti C et al.2013, Toxicology 303:162-168 3) Nasuti C et al. 2007, Toxicology 229(3):194-20
Revised conditions for MRI due to isorotation theorem
No full textWe re-analyze the physical conditions for Magneto-rotational Instability (MRI) within a steady axisymmetric stratified disk of plasma, in order to account for the so-called isorotation theory (the spatial profile of differential angular velocity depends on the magnetic flux surface). We develop the study of linear stability around an astrophysical background configuration, following the original derivation in [15], but implementing the isorotation condition as the orthogonality between the background magnetic field and the angular velocity gradient. We demonstrate that a dependence on the background magnetic field direction is restored in the dispersion relation and, hence, the emergence of MRI is also influenced by field orientation. © 2017 The Author(s
Semiclassical and quantum behavior of the Mixmaster model in the polymer approach for the isotropic Misner variable
No full textWe analyze the semi-classical and quantum behavior of the Bianchi IX Universe in the Polymer Quantum Mechanics framework, applied to the isotropic Misner variable, linked to the space volume of the model. The study is performed both in the Hamiltonian and field equations approaches, leading to the remarkable result of a still singular and chaotic cosmology, whose Poincaré return map asymptotically overlaps the standard Belinskii–Khalatnikov–Lifshitz one. In the quantum sector, we reproduce the original analysis due to Misner, within the revised Polymer approach and we arrive to demonstrate that the quantum numbers of the point-Universe still remain constants of motion. This issue confirms the possibility to have quasi-classical states up to the initial singularity. The present study clearly demonstrates that the asymptotic behavior of the Bianchi IX Universe towards the singularity is not significantly affected by the Polymer reformulation of the spatial volume dynamics both on a pure quantum and a semiclassical level. © 2018, The Author(s)
Bianchi I model as a prototype for a cyclical Universe
No full textWe analyze the dynamics of the Bianchi I model in the presence of stiff matter, an ultrarelativistic component and a small negative cosmological constant. We quantize this model in the framework of the polymer quantum mechanics, in order to introduce cut-off features in the minisuperspace dynamics. We then apply to the polymer Wheeler–DeWitt equation, emerging from the Dirac constraint, an adiabatic approximation a la Vilenkin, which treats the Universe volume as a quasi-classical variable, becoming de facto the dynamical clock for the pure quantum degrees of freedom, here identified in the Universe anisotropies. The main issue of the present analysis consists of determining a cyclical evolution for the Bianchi I model, oscillating between the Big-Bounce induced by the cut-off physics and the turning point due to the small cosmological constant. Furthermore, the mean value of the Universe anisotropy variables remains finite during the whole evolution, including the phase across the Big-Bounce. Such a feature, according to a suitable choice of the initial conditions makes the present cosmological paradigm, a viable scenario for the description of a possible primordial and late phases of the actual Universe. © 2017 The Author(s
Influence of toroidal magnetic field in multiaccreting tori
No full textWe analysed the effects of a toroidal magnetic field in the formation of several magnetized accretion tori, dubbed as ringed accretion discs (RADs), orbiting around one central Kerr supermassive black hole (SMBH) in active galactic nuclei (AGNs), where both corotating and counterotating discs are considered. Constraints on tori formation and emergence of RADs instabilities, accretion on to the central attractor and tori collision emergence, are investigated. The results of this analysis show that the role of the central BH spin-mass ratio, the magnetic field and the relative fluid rotation and tori rotation with respect the central BH, are crucial elements in determining the accretion tori features, providing ultimately evidence of a strict correlation between SMBH spin, fluid rotation, and magnetic fields in RADs formation and evolution. More specifically,we proved that magnetic field and discs rotation are in fact strongly constrained, as tori formation and evolution in RADs depend on the toroidal magnetic fields parameters. Eventually, this analysis identifies specific classes of tori, for restrict ranges of magnetic field parameter, that can be observed around some specific SMBHs identified by their dimensionless spin. © 2018 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society
Bianchi I cosmology in the presence of a causally regularized viscous fluid
No full textWe analyze the dynamics of a Bianchi I cosmology in the presence of a viscous fluid, causally regularized according to the Lichnerowicz approach. We show how the effect induced by shear viscosity is still able to produce a matter creation phenomenon, meaning that also in the regularized theory we address, the Universe is emerging from a singularity with a vanishing energy density value. We discuss the structure of the singularity in the isotropic limit, when bulk viscosity is the only retained contribution. We see that, as far as viscosity is not a dominant effect, the dynamics of the isotropic Universe possesses the usual non-viscous power-law behaviour but in correspondence to an effective equation of state, depending on the bulk viscosity coefficient. Finally., we show that, in the limit of a strong non-thermodynamical equilibrium of the Universe mimicked by a dominant contribution of the effective viscous pressure, a power-law inflation behaviour of the Universe appears, the cosmological horizons are removed and a significant amount of entropy is produced. © 2017, The Author(s)
α-synuclein and DNMT imbalance, following early life permethrin treatment, leads to Nurr1 down regulation
No full textEnvironmental factors interface the genotype-phenotype correlation and result conferring a stable memory of activity status of genes. Early-life exposure (postnatal day 6-21) to low doses of the pesticide permethrin leads to down regulation of Nurr1 expression and also dopamine levels. This is correlated with hyper methylation of CpG in the promoter region of Nurr1 in adolescent rats exposed to permethrin while no alteration in methylation was seen in the age-matched control group. In order to define the mechanisms associated with the decreased Nurr1 gene expression, DNMTs and -synuclein levels were measured in adolescent, adult and old rats. The results obtained confirm their imbalance depending on the treatment and the age of rats
Leukocyte Nurr1 as peripheral biomarker of early-life environmental exposure to permethrin insecticide
No full textThe effect of a low dose of the insecticide permethrin administered during early-life was evaluated on leukocytes
inflammation mediators on 300- and 500-day-old rats. Nurr1, NF-κB-p65, Nrf2, lipid peroxidation and GSH levels
increased with age but compared to the control group, treatment with permethrin induced a significant increase only
of Nurr1 and lipid peroxidation in oldest rats. TNF-α and Rantes increased, while IL-1β, IL-2, IL-13 decreased in oldest
treated rats. The results propose Nurr1, TNF-α, Rantes, GSH and plasma lipid peroxidation as peripheral biomarkers
for monitoring the impact of early-life environmental exposure to xenobiotics in old age
Early life permethrin exposure induces long-term brain changes in Nurr1, NF-kB and Nrf-2
No full textPesticide exposure during brain development represents an important risk factor for the onset of brain-aging processes. Here, the impact of permethrin administered to rats from 6th to 21st day of life, at a dose near to "no observed adverse effect level" (NOAEL), was studied when animals reached 500 day-old. The permethrin treatment induced a decrease in Nurr1 gene expression in striatum, an increase in hippocampus and cerebellum, while the protein level changed only in striatum where it was increased. NF-kB p65 gene expression was increased in cerebellum, while its protein level augmented in cerebellum and in prefrontal cortex and decreased in hippocampus of treated rats compared to control ones. Nrf-2 gene expression resulted significantly higher only in cerebellum of treated animals. The results suggest that early life permethrin treatment induces long-lasting effects leading to dopaminergic neuronal disorders, monitored by Nurr1 alteration. Moreover the impairment of NF-kB and Nrf-2, important for the balance between pro- and anti-inflammatory systems, confirms that the neonatal permethrin treatment can influence genes involved with the onset of brain-ageing processes
- …
