Cluster of Sphingomonas paucimobilis Bacteremias Linked to Diversion of Intravenous Hydromorphone

Abstract

Collagen is the most abundant protein in animals. Collagen hydrolysate has been found to have multiple functions in the skin, bones, joints, muscles, and blood vessels. Recently, it has been reported that the low molecular weight fraction of collagen hydrolysate exhibited anxiolytic activity, suggesting that collagen peptides affect brain functions. In the present study, we found that oral administration of ginger-degraded collagen hydrolysate (GDCH) significantly decreased depression-like behavior in a forced swim test, suggesting that GDCH exhibited antidepressant activity in mice. The antidepressant activity of GDCH was abolished by pre-treatment with an antagonist of the dopamine receptor, but not treatment with a serotonin receptor antagonist. GDCH significantly increased gene expression of glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) in the hippocampus, molecules that affect the differentiation and survival of neurons, relative to that in the control condition. Meanwhile, there were no changes in the gene expression of brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3, major factors related to depression-like behavior. We also found that GDCH exhibited antidepressant activity in corticosterone-administered mice in a model of stress. In addition, GDCH increased GDNF and CNTF expression in the stressed condition, suggesting that mechanisms of the antidepressant activity of GDCH were the same in unstressed and stressed conditions. These results imply that GDCH exhibits antidepressant activity in unstressed and stressed conditions in mice. The upregulation of neurotrophic genes in the hippocampus may contribute to the reduction of depression-like behavior via a dopamine signal pathway modulated by GDCH. Collagen is the most abundant animal protein and is the main constituent of skin, bone, cartilage, and the extracellular matrix. One-third of collagen's constituent amino acids are glycine in a repeating Gly-X-Y sequence, where X and Y are other amino acids. However , there is no tryptophan or cysteine in collagen. Hence, collagen protein has low nutritional value. However , it was reported that collagen hydrolysate with col-lagenase exhibited various efficacious functions in the skin, bones, joints, muscles, and blood vessels. Recently, Kakoi et al. reported that the low molecular weight fraction of collagen peptides exhibited anxiolytic activity (1), suggesting that collagen peptides affect brain function. It has been reported that ginger enzyme has potent protease activity and cleaves peptide bonds with proline at the P 2 position, that is, hydrolyzes collagen protein, which consists of approximately 20% proline. Moreover, oral administration of collagen hydrolysate prepared with ginger enzyme is efficiently absorbed in the form of short-chain peptides like di-and tripeptides (2, 3). We expected that this ginger-degraded collagen hydrolysate (GDCH) might have potent activity in the brain. Major depressive disorder, one of the most common psychiatric diseases, is characterized by dysregulation of emotion and mood with abnormalities of cognitive function, sleep, appetite, and metabolism, among others (4, 5). Depression is an epidemic health problem all over the world. It is estimated that there are around 322 million depressed patients in the world according to the World Health Organization. In the current study, we investigated whether collagen hydrolysate exhibits a fast-acting antidepressant-like effect by examining its effects in the forced swim test, a paradigm used in the development of antidepressants. It is known that chronic stress decreases hippocampal neurogenesis and this neurogenesis can be increased by the administration of antidepressants (5-7). Neurotrophic and nerve growth factors such as brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and nerve growth factor (NGF) regulate proliferation and differentiation of neural stem cells. We thus examined whether colla-gen hydrolysates exhibited antidepressant activity and