Parkinson’s disease (PD) is characterized by non-motor symptoms as well as motor deficits. The non-motor symptoms rarely appear individually and occur simultaneously with motor deficits or independently. However, a comprehensive research on the non-motor symptoms using an experimental model of PD remains poorly understood. The aim of the current study is to establish a chronic mouse model of PD mimicking the comprehensive non-motor symptoms of human PD by injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and probenecid (MPTP/p). The non-motor and motor symptoms were evaluated by performing buried food, short-term olfactory memory, hot plate, open field, tail suspension, Y maze, novel object recognition, bead expulsion, one-h stool collection, rotarod, rearing, catalepsy, and akinesia tests after 10 injections of MPTP/p into mice. The expression levels of α-synuclein, glial fibrillary acidic protein (GFAP), tyrosine hydroxylase (TH) or DJ-1 were analyzed by Western blotting or immunostaining. MPTP/p-treated mice achieved to reproduce the key features of non-motor symptoms including olfactory deficit, thermal hyperalgesia, anxiety, depression, cognitive decline, and gastrointestinal dysfunction in addition to motor deficits. The MPTP/p-treated mice also showed the high levels of α-synuclein and low levels of TH and DJ-1 in striatum, substantia nigra, olfactory bulb, hippocampus, amygdala, prefrontal cortex, locus coeruleus, or colon. In addition, the expression levels of phosphorylated-α-synuclein and GFAP were elevated in the striatum and substantia nigra in the MPTP/p-treated mice. Taken together, our study clarifies that the chronic MPTP/p-treated mice have a variety of non-motor dysfunctions as well as motor abnormalities by α-synuclein overexpression and dopaminergic depletion. Therefore, the study of comprehensive phenotypes of non-motor symptoms in one PD model would advance in-depth understandings of neuropathological alternations and contribute to future strategies for PD treatment.
Spin-torque oscillator (STO) is a promising new technology for the future RF oscillators, which is based on the spin-transfer torque (STT) effect in magnetic multilayered nanostructure. It is expected to provide a larger tunability, smaller size, lower power consumption, and higher level of integration than the semiconductor-based oscillators. In our previous work, a circuit-level model of the giant magnetoresistance (GMR) STO was proposed. In this paper, we present a physics-based circuit-level model of the magnetic tunnel junction (MTJ)-based STO. MTJ-STO model includes the effect of perpendicular torque that has been ignored in the GMR-STO model. The variations of three major characteristics, generation frequency, mean oscillation power, and generation linewidth of an MTJ-STO with respect to the amount of perpendicular torque, are investigated, and the results are applied to our model. The operation of the model was verified by HSPICE simulation, and the results show an excellent agreement with the experimental data. The results also prove that a full circuit-level simulation with MJT-STO devices can be made with our proposed model.
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