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- Di Liberto, Valentina, et al.
(författare)
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Involvement of estrogen receptors in the resveratrol-mediated increase in dopamine transporter in human dopaminergic neurons and in striatum of female mice
- 2012
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Ingår i: Neuropharmacology. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0028-3908 .- 1873-7064. ; 62:2, s. 1011-1018
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with resveratrol (RSV) has been shown to protect vulnerable neurons after various brain injuries and in neurodegenerative diseases. The mechanisms for the effects of RSV in brain are not fully understood, but RSV may affect the expression of various gene products. RSV is structurally related to the synthetic estrogen, diethylstilbestrol so the effects of RSV may be gender-specific. Here we studied the role of RSV in the regulation of dopamine transporter (DAT) in the striatum using male and female mice. The basic levels of DAT in the striatum showed no sex difference, but the levels increased significantly by RSV (20 mg/kg i.p.) in female but not in male mice. Pretreatment of mice with the selective estrogen receptor (ER), ER alpha- and ER beta antagonist ICI 182,780, led to a complete block of RSV effect on DAT protein levels, suggesting that ERs are involved in the up-regulation of DAT by RSV. Similar data was also obtained in culture using human MESC2.10 and mouse SN4741 dopaminergic cells after treatment with RSV. Data further showed that RSV specifically induced gene transcription of DAT in the dopaminergic cells. These results show that estrogen receptors are involved in the up-regulation of DAT by RSV in the dopaminergic neurons, demonstrating a sex-dependent effect of RSV in the brain that may be of clinical importance. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. (C) 2011 Elsevier Ltd. All rights reserved.
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| 2. |
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| 3. |
- Mudo, Giuseppa, et al.
(författare)
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Transgenic expression and activation of PGC-1 alpha protect dopaminergic neurons in the MPTP mouse model of Parkinson's disease
- 2012
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Ingår i: Cellular and Molecular Life Sciences (CMLS). - : SPRINGER BASEL AG. - 1420-682X .- 1420-9071. ; 69:7, s. 1153-1165
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial dysfunction and oxidative stress occur in Parkinson's disease (PD), but little is known about the molecular mechanisms controlling these events. Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) is a transcriptional coactivator that is a master regulator of oxidative stress and mitochondrial metabolism. We show here that transgenic mice overexpressing PGC-1 alpha in dopaminergic neurons are resistant against cell degeneration induced by the neurotoxin MPTP. The increase in neuronal viability was accompanied by elevated levels of mitochondrial antioxidants SOD2 and Trx2 in the substantia nigra of transgenic mice. PGC-1 alpha overexpression also protected against MPTP-induced striatal loss of dopamine, and mitochondria from PGC-1 alpha transgenic mice showed an increased respiratory control ratio compared with wild-type animals. To modulate PGC-1 alpha, we employed the small molecular compound, resveratrol (RSV) that protected dopaminergic neurons against the MPTP-induced cell degeneration almost to the same extent as after PGC-1 alpha overexpression. As studied in vitro, RSV activated PGC-1 alpha in dopaminergic SN4741 cells via the deacetylase SIRT1, and enhanced PGC-1 alpha gene transcription with increases in SOD2 and Trx2. Taken together, the results reveal an important function of PGC-1 alpha in dopaminergic neurons to combat oxidative stress and increase neuronal viability. RSV and other compounds acting via SIRT1/PGC-1 alpha may prove useful as neuroprotective agents in PD and possibly in other neurological disorders.
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| 4. |
- Vanaveski, Taavi, et al.
(författare)
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PGC-1 alpha Signaling Increases GABA(A) Receptor Subunit alpha 2 Expression, GABAergic Neurotransmission and Anxiety-Like Behavior in Mice
- 2021
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Ingår i: Frontiers in Molecular Neuroscience. - : FRONTIERS MEDIA SA. - 1662-5099. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) is a master regulator of mitochondria biogenesis and cell stress playing a role in metabolic and degenerative diseases. In the brain PGC-1 alpha expression has been localized mainly to GABAergic interneurons but its overall role is not fully understood. We observed here that the protein levels of gamma-aminobutyric acid (GABA) type A receptor-alpha 2 subunit (GABAR alpha 2) were increased in hippocampus and brain cortex in transgenic (Tg) mice overexpressing PGC-1 alpha in neurons. Along with this, GABAR alpha 2 expression was enhanced in the hippocampus of the PGC-1 alpha Tg mice, as shown by quantitative PCR. Double immunostaining revealed that GABAR alpha 2 co-localized with the synaptic protein gephyrin in higher amounts in the striatum radiatum layer of the hippocampal CA1 region in the Tg compared with Wt mice. Electrophysiology revealed that the frequency of spontaneous and miniature inhibitory postsynaptic currents (mIPSCs) was increased in the CA1 region in the Tg mice, indicative of an augmented GABAergic transmission. Behavioral tests revealed an increase for anxiety-like behavior in the PGC-1 alpha Tg mice compared with controls. To study whether drugs acting on PPAR gamma can affect GABAR alpha 2, we employed pioglitazone that elevated GABAR alpha 2 expression in primary cultured neurons. Similar results were obtained using the specific PPAR gamma agonist, N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino) ethyl]-L-tyrosine hydrate (GW1929). These results demonstrate that PGC-1 alpha regulates GABAR alpha 2 subunits and GABAergic neurotransmission in the hippocampus with behavioral consequences. This indicates further that drugs like pioglitazone, widely used in the treatment of type 2 diabetes, can influence GABAR alpha 2 expression via the PPAR gamma/PGC-1 alpha system.
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| 5. |
- Wiklund, Olof, et al.
(författare)
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Hybrid modelling of the rolling force in a plate mill
- 2002
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Ingår i: Scandinavian journal of metallurgy. - : Wiley. - 0371-0459 .- 1600-0692. ; 31:2, s. 153-160
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Tidskriftsartikel (refereegranskat)abstract
- Different empirical and hybrid modelling techniques were evaluated in order to improve the modelling compared with the present situation in the plate rolling mill at Rautaruukki, Raahe. Logged data from the production were used to develop new models and to compare them with each other and with the present model. The data describe the chemical composition and various process parameters of the rolling process, including thermal, geometric and kinematic parameters. Various neural networks and multivariate models were evaluated in order to take non-linear effects into account. Hybrid methods use a combination of physically based models and empirical models. The simple physically based formula, force = area x yield strength factor, proved useful. A more advanced model solving von Karman's differential equation was evaluated as a stand-alone model and as part of a hybrid model. The measured force of the previous rolling pass was tested as an additional input variable. Various aspects of the different modelling techniques are discussed and compared. Simple but improved models are described as suitable candidates to replace the present on-line model. © Blackwell Munksgaard, 2002.
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