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Lovastatin fails to improve motor performance and survival in methyl-CpG-binding protein2-null mice.

ABSTRACT: Previous studies provided evidence for the alteration of brain cholesterol homeostasis in 129.Mecp2-null mice, an experimental model of Rett syndrome. The efficacy of statins in improving motor symptoms and prolonging survival of mutant mice suggested a potential role of statins in the therapy of Rett syndrome. In the present study, we show that Mecp2 deletion had no effect on brain and reduced serum cholesterol levels and lovastatin (1.5 mg/kg, twice weekly as in the previous study) had no effects on motor deficits and survival when Mecp2 deletion was expressed on a background strain (C57BL/6J; B6) differing from that used in the earlier study. These findings indicate that the effects of statins may be background specific and raise important issues to consider when contemplating clinical trials. The reduction of the brain cholesterol metabolite 24S-hydroxycholesterol (24S-OHC) found in B6.Mecp2-null mice suggests the occurrence of changes in brain cholesterol metabolism and the potential utility of using plasma levels of 24S-OHC as a biomarker of brain cholesterol homeostasis in RTT.

SUBMITTER: Villani C

PROVIDER: S-EPMC5132339 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Lovastatin fails to improve motor performance and survival in methyl-CpG-binding protein2-null mice.

Villani Claudia C Sacchetti Giuseppina G Bagnati Renzo R Passoni Alice A Fusco Federica F Carli Mirjana M Invernizzi Roberto William RW

eLife 20161128

Previous studies provided evidence for the alteration of brain cholesterol homeostasis in 129.Mecp2-null mice, an experimental model of Rett syndrome. The efficacy of statins in improving motor symptoms and prolonging survival of mutant mice suggested a potential role of statins in the therapy of Rett syndrome. In the present study, we show that Mecp2 deletion had no effect on brain and reduced serum cholesterol levels and lovastatin (1.5 mg/kg, twice weekly as in the previous stud ...[more]

PMID: 27892851

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Project description:Transcranial direct current stimulation (tDCS) is a brain stimulation technique that can enhance motor activity by stimulating the motor path. Thus, tDCS has the potential of improving the performance of brain-computer interfaces during motor neurorehabilitation. tDCS effects depend on several aspects, including the current density, which usually varies between 0.02 and 0.08 mA/cm2, and the location of the stimulation electrodes. Hence, testing tDCS montages at several current levels would allow the selection of current parameters for improving stimulation outcomes and the comparison of montages. In a previous study, we found that cortico-cerebellar tDCS shows potential of enhancing right-hand motor imagery. In this paper, we aim to evaluate the effects of the focal stimulation of the motor cortex over motor imagery. In particular, the effect of supplying tDCS with a 4 × 1 ring montage, which consists in placing an anode on the motor cortex and four cathodes around it, over motor imagery was assessed with different current densities. Electroencephalographic (EEG) classification into rest or right-hand/feet motor imagery was evaluated on five healthy subjects for two stimulation schemes: applying tDCS for 10 min on the (1) right-hand or (2) feet motor cortex before EEG recording. Accuracy differences related to the tDCS intensity, as well as ? and ? band power changes, were tested for each subject and tDCS modality. In addition, a simulation of the electric field induced by the montage was used to describe its effect on the brain. Results show no improvement trends on classification for the evaluated currents, which is in accordance with the observation of variable EEG band power results despite the focused stimulation. The lack of effects is probably related to the underestimation of the current intensity required to apply a particular current density for small electrodes and the relatively short inter-electrode distance. Hence, higher current intensities should be evaluated in the future for this montage.

Dataset Information

Lovastatin fails to improve motor performance and survival in methyl-CpG-binding protein2-null mice.

Publications

Lovastatin fails to improve motor performance and survival in <i>methyl-CpG-binding protein2</i>-null mice.

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