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Objective Atomoxetine and fluoxetine are psychopharmacologic agents associated with loss of appetite and weight. Adenosine monophosphate-activated protein kinase (AMPK) is the cellular energy sensor that regulate metabolism and energy, being activated by fasting and inhibited by feeding in the hypothalamus.Methods Human brain cell lines (SH-SY5Y and U-87 MG cells) were used to study the outcome of atomoxetine and fluoxetine treatment in the activity of AMPK-acetyl-CoA carboxylase (ACC)- carnitine palmitoyl transferase 1 (CPT1) pathway and upstream regulation by calcium/calmodulin-dependent kinase kinase β (CaMKKβ) using immunoblotting and CPT1 enzymatic activity measures.Results Phosphorylation of AMPK and ACC increased significantly after atomoxetine and fluoxetine treatment in the first 30–60 minutes of treatment in the two cell lines. Activation of AMPK and inhibition of ACC was associated with an increase by 5-fold of mitochondrial CPT1 activity. Although the neuronal isoform CPT1C could be detected by immunoblotting, activity was not changed by the drug treatments. In addition, the increase in phospho-AMPK and phospho-ACC expression induced by atomoxetine was abolished by treatment with STO-609, a CaMKKβ inhibitor, indicating that AMPK-ACC-CPT1 pathway is activated through CaMKKβ phosphorylation.Conclusion These findings indicate that at the cellular level atomoxetine and fluoxetine treatments may activate AMPK-ACC-CPT1 pathways through CaMKKβ in human SH-SY5Y and U-87 MG cells.

Supplemental Digital Content is Available in the Text. Acupuncture treatment for 6-month period altered DNA methylation patterns, particularly in the prefrontal cortex, in a mouse model of chronic neuropathic pain., Chronic pain reduces life quality and is an important clinical problem associated with emotional and cognitive dysfunction. Epigenetic regulation of DNA methylation is involved in the induction of abnormal behaviors and pathological gene expression. We examined whether acupuncture can restore epigenetic changes caused by chronic pain, and identified the underlying mechanisms in neuropathic pain mice. Acupuncture treatment for 6 months (3 days/week) improved mechanical/cold allodynia and the emotional/cognitive dysfunction caused by left partial sciatic nerve ligation (PSNL)-induced neuropathic pain. The effects of acupuncture were associated with global DNA methylation recovery in the prefrontal cortex (PFC). Analysis of DNA methylation patterns in PFC indicated that 1364 overlapping genes among 4442 and 4416 methylated genes in the PSNL vs sham and PSNL vs acupuncture points groups, respectively, were highly associated with the DNA methylation process. Acupuncture restored the reduced expression of 5-methylcytosine, methyl-cytosine-phospho-guanine binding protein 2, and DNA methyltransferase family enzymes induced by PSNL in PFC. Methylation levels of Nr4a1 and Chkb associated with mitochondrial dysfunction were decreased in PFC of the PSNL mice, and increased by acupuncture. By contrast, high expression of Nr4a1 and Chkb mRNA in PSNL mice decreased after acupuncture. We also found that acupuncture inhibited the expression of Ras pathway-related genes such as Rasgrp1 and Rassf1. Finally, the expression of Nr4a1, Rasgrp1, Rassf1, and Chkb mRNA increased in the neuronal cells treated with Mecp2 small interfering RNA. These results suggest that acupuncture can relieve chronic pain-induced comorbid conditions by altering DNA methylation of Nr4a1, Rasgrp1, Rassf1, and Chkb in the PFC.

We systematically investigated the resistive switching properties of thin TiO₂ films on Pt/Ti/SiO₂/Si substrates that were embedded with a Co ultra thin layer. An in-situ sputtering technique was used to grow both films without breaking the chamber vacuum. A stable bipolar switching in the current-voltage curve was clearly observed in TiO₂ films with an embedded Co ultra thin layer, addressing the high and low resistive state under a bias voltage sweep. We propose that the underlying origin involved in the bipolar switching may be attributed to the interface redox reaction between the Co and TiO₂ layers. The improved reproducible switching properties of our novel structures under forward and reverse bias stresses demonstrated the possibility of future non-volatile memory elements in a simple capacitive-like structure.

We report the magnetic behaviors of Fe/sub 3/O/sub 4/ thin films grown by zero field growth (ZFG) and field growth (FG) techniques during the sputtering process. In FG conditions, an in situ 300 Oe field during growth is applied to a substrate, inducing an easy axis of magnetization. Structural observations obtained by high-resolution transmission electron microscopy measurements clearly depicted a significant reduction of the grain boundaries and voids in the Fe/sub 3/O/sub 4/ films grown under FG conditions, thus explaining the saturated magnetization of the Fe/sub 3/O/sub 4/ films at about 0.01 T. This behavior was expected due to a remarkable reduction of the antiferromagnetic exchange couplings between grains for FG conditions. In addition, the zero-field-cooled magnetization of the ZFG samples showed an abrupt change at about 285 K, confirming the existence of defects or other phases in the ZFG films.

We present some unusual spin-polarized transport phenomena in asymmetric double barrier magnetic tunneling junctions (ADBMTJs) with CoFe/AlOx/ferromagnetic nanoparticle (FM-NPs)/AlOx/Ta structures. The conductance curves and the magnetoresistance ratio clearly oscillate with applied bias voltage, indicating the presence of Coulomb blockade effects due to isolated ferromagnetic nanoparticles in the parallel configuration in the ADBMTJ. The oscillation period is about 1.5 mV at 2 K.

In this report, a phenomenon of superparamagnetism through Co nanodots (NDs) prepared by laser irradiation method is studied. These NDs are simply prepared on Si substrates by applying an external laser irradiation on ultra thin Co films at room temperature. The laser irradiation on these ferromagnetic thin films locally melt the film at an extremely shot time so that the melted films get together to form the NDs by the strain effect. Structural properties of these NDs are investigated by scanning electron microscope, atomic force microscope (AFM), and transmission electron microscope (TEM). The magnetization as a function of temperature with differential Co NDs is measured at field cooling (FC) and zero field cooling (ZFC) methods. Results show that at 0.3 T field, remanence magnetization M/sub r/ is saturated. The diameter of Co NDs is increased with an increase temperature of zero remanence value. The zero remanent value at each temperature demonstrates that below this temperature, the magnetic moments are at least partially blocked. In addition, Co NDs have relatively high anisotropy energy because of a field growth method which is the additional source of the anisotropy.