Effects of cariprazine on extracellular levels of glutamate, GABA, dopamine, noradrenaline and serotonin in the medial prefrontal cortex in the rat phencyclidine model of schizophrenia studied by microdialysis and simultaneous recordings of locomotor activity

Aberrant glutamatergic, dopaminergic, and GABAergic neurotransmission has been implicated in schizophrenia. Cariprazine reverses the behavioral effects observed in the rat phencyclidine (PCP)-induced model of schizophrenia; however, little is known about its in vivo neurochemistry. The study aims to compare the effects of cariprazine and aripiprazole on PCP-induced changes in the extracellular levels of glutamate, dopamine, serotonin, noradrenaline, and GABA in the rat medial prefrontal cortex (mPFC), and on locomotor activation. Microdialysis was performed in awake rats with probes placed into the mPFC. Rats (n = 7/group) received vehicle (saline), cariprazine (0.05, 0.2, or 0.8 mg/kg), or aripiprazole (3 or 20 mg/kg) via gavage. After 60 min, 5 mg/kg PCP was administered intraperitoneally (i.p.). Samples were taken before drug administration, during pretreatment, and after PCP injection. Locomotor activity recording and microdialysis sampling occurred simultaneously. PCP treatment increased extracellular levels of all the neurotransmitters tested except GABA, for which there were no significant changes. Cariprazine and aripiprazole dose-dependently inhibited the PCP-induced increases of tested neurotransmitters. Overall effects were significant for higher cariprazine doses and both aripiprazole doses for glutamate and noradrenaline, for higher cariprazine doses and 20 mg/kg aripiprazole for dopamine, and for 0.8 mg/kg cariprazine and 20 mg/kg aripiprazole for serotonin and locomotor activity. Both cariprazine and aripiprazole dose-dependently attenuated PCP-induced hyperlocomotion and acute increases in glutamate, dopamine, noradrenaline, and serotonin levels in the mPFC; cariprazine was approximately 5-fold more potent than aripiprazole

Use of MMG signals for the control of powered orthotic devices: Development of a rectus femoris measurement protocol

Copyright © 2009 Rehabilitation Engineering and Assistive Technology Society (RESNA). This is an Author's Accepted Manuscript of an article published in Assistive Technology, 21(1), 1 - 12, 2009, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/10400430902945678.A test protocol is defined for the purpose of measuring rectus femoris mechanomyographic (MMG) signals. The protocol is specified in terms of the following: measurement equipment, signal processing requirements, human postural requirements, test rig, sensor placement, sensor dermal fixation, and test procedure. Preliminary tests of the statistical nature of rectus femoris MMG signals were performed, and Gaussianity was evaluated by means of a two-sided Kolmogorov-Smirnov test. For all 100 MMG data sets obtained from the testing of two volunteers, the null hypothesis of Gaussianity was rejected at the 1%, 5%, and 10% significance levels. Most skewness values were found to be greater than 0.0, while all kurtosis values were found to be greater than 3.0. A statistical convergence analysis also performed on the same 100 MMG data sets suggested that 25 MMG acquisitions should prove sufficient to statistically characterize rectus femoris MMG. This conclusion is supported by the qualitative characteristics of the mean rectus femoris MMG power spectral densities obtained using 25 averages

Design of Vibration Control and Electricity Generating Device

This paper deals with a vibration control device which generates electricity by using absorbed vibration energy. This device consists of a Hula-Hoop and generator. In this paper, we researched the design of the device. As the result of the numerical calculation, the following were made clear : (1) The influences of parameters of this device, damping force related to the capacity of the generator, the length of Hula-Hoop, and moment of inertia of the Hula-Hoop on the vibration control and on generating electricity were made clear. (2) The operating curve was shown by composing the resonance curve when the Hula-Hoop rotates and that when it does not. (3) The design diagram that describes the vibration control effect of this device was shown

Critical role of somatostatin receptor 2 in the vulnerability of the central noradrenergic system: new aspects on Alzheimer's disease

Alzheimer's disease and other age-related neurodegenerative disorders are associated with deterioration of the noradrenergic locus coeruleus (LC), a probable trigger for mood and memory dysfunction. LC noradrenergic neurons exhibit particularly high levels of somatostatin binding sites. This is noteworthy since cortical and hypothalamic somatostatin content is reduced in neurodegenerative pathologies. Yet a possible role of a somatostatin signal deficit in the maintenance of noradrenergic projections remains unknown. Here, we deployed tissue microarrays, immunohistochemistry, quantitative morphometry and mRNA profiling in a cohort of Alzheimer's and age-matched control brains in combination with genetic models of somatostatin receptor deficiency to establish causality between defunct somatostatin signalling and noradrenergic neurodegeneration. In Alzheimer's disease, we found significantly reduced somatostatin protein expression in the temporal cortex, with aberrant clustering and bulging of tyrosine hydroxylase-immunoreactive afferents. As such, somatostatin receptor 2 (SSTR2) mRNA was highly expressed in the human LC, with its levels significantly decreasing from Braak stages III/IV and onwards, i.e., a process preceding advanced Alzheimer's pathology. The loss of SSTR2 transcripts in the LC neurons appeared selective, since tyrosine hydroxylase, dopamine beta-hydroxylase, galanin or galanin receptor 3 mRNAs remained unchanged. We modeled these pathogenic changes in Sstr2 -/- mice and, unlike in Sstr1 -/- or Sstr4 -/- genotypes, they showed selective, global and progressive degeneration of their central noradrenergic projections. However, neuronal perikarya in the LC were found intact until late adulthood (<8 months) in Sstr2 -/- mice. In contrast, the noradrenergic neurons in the superior cervical ganglion lacked SSTR2 and, as expected, the sympathetic innervation of the head region did not show any signs of degeneration. Our results indicate that SSTR2-mediated signaling is integral to the maintenance of central noradrenergic projections at the system level, and that early loss of somatostatin receptor 2 function may be associated with the selective vulnerability of the noradrenergic system in Alzheimer's disease

Prediction of causative genes in inherited retinal disorder from fundus photography and autofluorescence imaging using deep learning techniques

Background/Aims: To investigate the utility of a data-driven deep learning approach in patients with inherited retinal disorder (IRD) and to predict the causative genes based on fundus photography and fundus autofluorescence (FAF) imaging. / Methods: Clinical and genetic data from 1302 subjects from 729 genetically confirmed families with IRD registered with the Japan Eye Genetics Consortium were reviewed. Three categories of genetic diagnosis were selected, based on the high prevalence of their causative genes: Stargardt disease (ABCA4), retinitis pigmentosa (EYS) and occult macular dystrophy (RP1L1). Fundus photographs and FAF images were cropped in a standardised manner with a macro algorithm. Images for training/testing were selected using a randomised, fourfold cross-validation method. The application program interface was established to reach the learning accuracy of concordance (target: >80%) between the genetic diagnosis and the machine diagnosis (ABCA4, EYS, RP1L1 and normal). / Results: A total of 417 images from 156 Japanese subjects were examined, including 115 genetically confirmed patients caused by the three prevalent causative genes and 41 normal subjects. The mean overall test accuracy for fundus photographs and FAF images was 88.2% and 81.3%, respectively. The mean overall sensitivity/specificity values for fundus photographs and FAF images were 88.3%/97.4% and 81.8%/95.5%, respectively. / Conclusion: A novel application of deep neural networks in the prediction of the causative IRD genes from fundus photographs and FAF, with a high prediction accuracy of over 80%, was highlighted. These achievements will extensively promote the quality of medical care by facilitating early diagnosis, especially by non-specialists, access to care, reducing the cost of referrals, and preventing unnecessary clinical and genetic testing

Influence of residual Ga_2O_3 and Cs on the increase in the maximum quantum efficiency of NEA-GaAs by a two-step thermal cleaning process

We investigated the relationship between the increase in the maximum quantum efficiency of negative electron affinity (NEA)-GaAs depending on the thermal cleaning conditions and residual species, e.g., Ga_2O_3 and Cs atoms, on the GaAs surface using temperature-programmed desorption. We found that the increase in the maximum quantum efficiency occurs during thermal cleaning at 500–600℃ for ～8.5 min. The increase in ratio was maximum when the amount of Ga_2O_3 on the GaAs surface was maximum. In the case that Cs atoms remained, when the thermal cleaning was performed in a temperature range where Ga_2O_3 was not formed, the effect facilitating an NEA surface formation was observed. However, the residual Cs atoms might not be affected at an increased maximum quantum efficiency. From the above results, we considered that the double-dipole structures of Cs-Ga_2O_3 and Cs-O are significant to the high quantum efficiency. The Cs-O dipoles are considered to form easily when Ga_2O_3 is on the GaAs surface before the NEA activation, and the amount of Cs-O dipoles required to reduce the vacuum level below the conduction band minimum increase more than usually NEA surface. As a result, the maximum quantum efficiency increases