Enhancing plasticity mechanisms in the mouse motor cortex by anodal transcranial direct current stimulation: the contribution of nitric-oxide signaling.

Consistent body of evidence shows that transcranial direct-current stimulation (tDCS) over the primary motor cortex (M1) facilitates motor learning and promotes recovery after stroke. However, the knowledge of molecular mechanisms behind tDCS effects needs to be deepened for a more rational use of this technique in clinical settings. Here we characterized the effects of anodal tDCS of M1, focusing on its impact on glutamatergic synaptic transmission and plasticity. Mice subjected to tDCS displayed increased long-term potentiation (LTP) and enhanced basal synaptic transmission at layer II/III horizontal connections. They performed better than sham-stimulated mice in the single-pellet reaching task and exhibited increased forelimb strength. Dendritic spine density of layer II/III pyramidal neurons was also increased by tDCS. At molecular level, tDCS enhanced: 1) BDNF expression, 2) phosphorylation of CREB, CaMKII, and GluA1, and 3) S-nitrosylation of GluA1 and HDAC2. Blockade of nitric oxide synthesis by L-NAME prevented the tDCS-induced enhancement of GluA1 phosphorylation at Ser831 and BDNF levels, as well as of miniature excitatory postsynaptic current (mEPSC) frequency, LTP and reaching performance. Collectively, these findings demonstrate that anodal tDCS engages plasticity mechanisms in the M1 and highlight a role for nitric oxide (NO) as a novel mediator of tDCS effects

Olfactory memory is enhanced in mice exposed to extremely lowfrequency electromagnetic fields via Wnt/\u3b2-catenin dependent modulation of subventricular zone neurogenesis.

Exposure to extremely low-frequency electromagnetic fields (ELFEF) influences the expression of key target genes controlling adult neurogenesis and modulates hippocampus-dependent memory. Here, we assayed whether ELFEF stimulation affects olfactory memory by modulating neurogenesis in the subventricular zone (SVZ) of the lateral ventricle, and investigated the underlying molecular mechanisms. We found that 30 days after the completion of an ELFEF stimulation protocol (1 mT; 50\u2009Hz; 3.5\u2009h/day for 12 days), mice showed enhanced olfactory memory and increased SVZ neurogenesis. These effects were associated with upregulated expression of mRNAs encoding for key regulators of adult neurogenesis and were mainly dependent on the activation of the Wnt pathway. Indeed, ELFEF stimulation increased Wnt3 mRNA expression and nuclear localization of its downstream target \u3b2-catenin. Conversely, inhibition of Wnt3 by Dkk-1 prevented ELFEF-induced upregulation of neurogenic genes and abolished ELFEF\u2019s effects on olfactory memory. Collectively, our findings suggest that ELFEF stimulation increases olfactory memory via enhanced Wnt/\u3b2-catenin signaling in the SVZ and point to ELFEF as a promising tool for enhancing SVZ neurogenesis and olfactory function

Quantitative angiography and optical coherence tomography for the functional assessment of nonobstructive coronary stenoses: comparison with fractional flow reserve.

12BACKGROUND: The purpose was to compare 3-dimensional quantitative coronary angiography (3D-QCA) with optical coherence tomography (OCT) for the functional assessment of nonobstructive coronary stenoses, as evaluated by fractional flow reserve (FFR). METHODS: Fifty-five nonobstructive coronary stenoses (30%-50% diameter stenosis by visual estimation) were assessed in 36 patients using FFR, 2-dimensional QCA (2D-QCA), 3D-QCA, and OCT. RESULTS: Angiographic stenosis severity by 2D-QCA was 34% ± 13% diameter stenosis, and minimal lumen diameter (MLD) was 1.77 ± 0.58 mm. Fractional flow reserve values were 0.85 ± 0.10. Correlation coefficients between FFR and MLD or minimal lumen area (MLA) were highly significant for both 2D- and 3D-QCA (all P 1.53 mm or MLA >2.43 mm(2) are unlikely to be hemodynamically significant. CONCLUSIONS: In nonobstructive coronary stenoses, anatomical parameters derived from 3D-QCA can best identify lesions with preserved FFR values.nonenonePyxaras SA;Tu S;Barbato E;Barbati G;Di Serafino L;De Vroey F;Toth G;Mangiacapra F;Sinagra G;De Bruyne B;Reiber JH;Wijns WPyxaras, Sa; Tu, S; Barbato, E; Barbati, Giulia; Di Serafino, L; De Vroey, F; Toth, G; Mangiacapra, F; Sinagra, Gianfranco; De Bruyne, B; Reiber, Jh; Wijns, W