Correlation between immune-related genes and depression-like features in an animal model and in humans.

A growing body of evidence suggests that immune-related genes play pivotal roles in the pathophysiology of depression. In the present study, we investigated a plausible connection between gene expression, DNA methylation, and brain structural changes in the pathophysiology of depression using a combined approach of murine and human studies. We ranked the immobility behaviors of 30 outbred Crl:CD1 (ICR) mice in the forced swim test (FST) and harvested their prefrontal cortices for RNA sequencing. Of the 24,532 analyzed genes, 141 showed significant correlations with FST immobility time, as determined through linear regression analysis with p ≤ 0.01. The identified genes were mostly involved in immune responses, especially interferon signaling pathways. Moreover, induction of virus-like neuroinflammation in the brains of two separate mouse cohorts (n = 30 each) using intracerebroventricular polyinosinic:polycytidylic acid injection resulted in increased immobility during FST and similar expression of top immobility-correlated genes. In human blood samples, candidate gene (top 5%) expression profiling using DNA methylation analysis found the interferon-related USP18 (cg25484698, p = 7.04 × 10-11, Δß = 1.57 × 10-2; cg02518889, p = 2.92 × 10-3, Δß =  - 8.20 × 10-3) and IFI44 (cg07107453, p = 3.76 × 10-3, Δß =  - 4.94 × 10-3) genes to be differentially methylated between patients with major depressive disorder (n = 350) and healthy controls (n = 161). Furthermore, cortical thickness analyses using T1-weighted images revealed that the DNA methylation scores for USP18 were negatively correlated with the thicknesses of several cortical regions, including the prefrontal cortex. Our results reveal the important role of the interferon pathway in depression and suggest USP18 as a potential candidate target. The results of the correlation analysis between transcriptomic data and animal behavior carried out in this study provide insights that could enhance our understanding of depression in humans.

Minoxidil Regulates Aging-Like Phenotypes in Rat Cortical Astrocytes In Vitro.

Mainly due to the slanted focus on the mechanism and regulation of neuronal aging, research on astrocyte aging and its modulation during brain aging is scarce. In this study, we established aged astrocyte culture model by long-term culturing. Cellular senescence was confirmed through SA-ß-gal staining as well as through the examination of morphological, molecular, and functional markers. RNA sequencing and functional analysis of astrocytes were performed to further investigate the detailed characteristics of the aged astrocyte model. Along with aged phenotypes, decreased astrocytic proliferation, migration, mitochondrial energetic function and support for neuronal survival and differentiation has been observed in aged astrocytes. In addition, increased expression of cytokines and chemokine-related factors including plasminogen activator inhibitor -1 (PAI-1) was observed in aged astrocytes. Using the RNA sequencing results, we searched potential drugs that can normalize the dysregulated gene expression pattern observed in long-term cultured aged astrocytes. Among several candidates, minoxidil, a pyrimidine-derived anti-hypertensive and anti-pattern hair loss drug, normalized the increased number of SA-ß-gal positive cells and nuclear size in aged astrocytes. In addition, minoxidil restored up-regulated activity of PAI-1 and increased mitochondrial superoxide production in aged astrocytes. We concluded that long term culture of astrocytes can be used as a reliable model for the study of astrocyte senescence and minoxidil can be a plausible candidate for the regulation of brain aging.

Mid-Air Tactile Stimulation Using Indirect Laser Radiation.

In this paper, we demonstrate that a laser irradiated on a thin light-absorbing elastic medium attached on the skin can elicit a tactile sensation of mechanical tap. First, we present simulation results that show laser irradiation to the elastic medium creates inner elastic waves on the basis of thermoelastic effects and these elastic waves trigger the bending deformation of the medium, which then stimulates the skin. Second, we analyze the physical properties of the associated stimulus by measuring its force profile. Third, we identify the perceptual characteristics of the stimulus in comparison to those of mechanical and electrical stimuli by means of a perceptual experiment employing dissimilarity rating. All the evidence indicates that indirect laser radiation provides a sensation of short mechanical tap. Furthermore, little individual difference was observed in the results of the perceptual experiment. To the best of our knowledge, this study is the first in reporting the feasibility of indirect laser radiation for mid-air tactile rendering.

Survival and prognostic analysis of adjacent segments after spinal fusion.

BACKGROUND: To examine the survival function and prognostic factors of the adjacent segments based on a second operation after thoracolumbar spinal fusion. METHODS: This retrospective study reviewed 3,188 patients (3,193 cases) who underwent a thoracolumbar spinal fusion at the author's hospital. Survival analysis was performed on the event of a second operation due to adjacent segment degeneration. The prognostic factors, such as the cause of the disease, surgical procedure, age, gender and number of fusion segments, were examined. Sagittal alignment and the location of the adjacent segment were measured in the second operation cases, and their association with the types of degeneration was investigated. RESULTS: One hundred seven patients, 112 cases (3.5%), underwent a second operation due to adjacent segment degeneration. The survival function was 97% and 94% at 5 and 10 years after surgery, respectively, showing a 0.6% linear reduction per year. The significant prognostic factors were old age, degenerative disease, multiple-level fusion and male. Among the second operation cases, the locations of the adjacent segments were the thoracolumbar junctional area and lumbosacral area in 11.6% and 88.4% of cases, respectively. Sagittal alignment was negative or neutral, positive and strongly positive in 47.3%, 38.9%, and 15.7%, respectively. Regarding the type of degeneration, spondylolisthesis or kyphosis, retrolisthesis, and neutral balance in the sagittal view was noted in 13.4%, 36.6%, and 50% of cases, respectively. There was a significant difference according to the location of the adjacent segment (p = 0.000) and sagittal alignment (p = 0.041). CONCLUSIONS: The survival function of the adjacent segments was 94% at 10 years, which had decreased linearly by 0.6% per a year. The likelihood of a second operation was high in those with old age, degenerative disease, multiple-level fusion and male. There was a tendency for the type of degeneration to be spondylolisthesis or kyphosis in cases of the thoracolumbar junctional area and strongly positive sagittal alignment, but retrolisthesis in cases of the lumbosacral area and neutral or positive sagittal alignment.