Fluoxetine partially alleviates inflammation in the kidney of socially stressed male C57 BL/6 mice.

Stress-related illnesses are linked to the onset and progression of renal diseases and depressive disorders. To investigate stress-induced changes in the renal transcriptome associated with the development of depressive behaviors, we generated here a chronic social defeat stress (CSDS) model of C57 BL/6 male mice and then performed RNA sequencing of the kidneys to obtain an inflammation-related transcriptome. Administration of the antidepressant drug fluoxetine (10 mg·kg-1 ·day-1 ) during CSDS induction could partially alleviate renal inflammation and reverse CSDS-induced depression-like behaviors. Moreover, fluoxetine also modulated gene expression of stress-related hormone receptors, including prolactin and melanin-concentrating hormone. These results suggest that CSDS can induce gene expression changes associated with inflammation in the kidney of C57 BL/6 male mice, and this inflammation can be treated effectively by fluoxetine.

Nonerythropoietic Erythropoietin Mimetic Peptide ARA290 Ameliorates Chronic Stress-Induced Depression-Like Behavior and Inflammation in Mice.

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder. But the treatment of depression remains challenging. Anti-inflammatory treatments frequently produce antidepressant effects. EPO-derived helix-B peptide ARA290 has been reported to retain the anti-inflammatory and tissue-protective functions of EPO without erythropoiesis-stimulating effects. The effects of ARA290 on MDD remain elusive. This study established chronic unpredictable mild stress and chronic social defeat stress mouse models. Daily administration of ARA290 during chronic stress induction in two mouse models ameliorated depression-like behavior, similar to fluoxetine. With marginal effects on peripheral blood hemoglobin and red cells, ARA290 and fluoxetine reversed chronic stress-induced increased frequencies and/or numbers of CD11b+Ly6Ghi neutrophils and CD11b+Ly6Chi monocytes in the bone marrow and meninges. Furthermore, both drugs reversed chronic stress-induced microglia activation. Thus, ARA290 ameliorated chronic stress-induced depression-like behavior in mice through, at least partially, its anti-inflammatory effects.

Adaptive hyperparameter updating for training restricted Boltzmann machines on quantum annealers.

Restricted Boltzmann Machines (RBMs) have been proposed for developing neural networks for a variety of unsupervised machine learning applications such as image recognition, drug discovery, and materials design. The Boltzmann probability distribution is used as a model to identify network parameters by optimizing the likelihood of predicting an output given hidden states trained on available data. Training such networks often requires sampling over a large probability space that must be approximated during gradient based optimization. Quantum annealing has been proposed as a means to search this space more efficiently which has been experimentally investigated on D-Wave hardware. D-Wave implementation requires selection of an effective inverse temperature or hyperparameter ([Formula: see text]) within the Boltzmann distribution which can strongly influence optimization. Here, we show how this parameter can be estimated as a hyperparameter applied to D-Wave hardware during neural network training by maximizing the likelihood or minimizing the Shannon entropy. We find both methods improve training RBMs based upon D-Wave hardware experimental validation on an image recognition problem. Neural network image reconstruction errors are evaluated using Bayesian uncertainty analysis which illustrate more than an order magnitude lower image reconstruction error using the maximum likelihood over manually optimizing the hyperparameter. The maximum likelihood method is also shown to out-perform minimizing the Shannon entropy for image reconstruction.