Anti-CRHBP monoclonal antibody, clone 406209

It has been suggested by studies in animals and humans that substance P (SP) and its receptor neurokinin 1 (NK1R) play an important role in the pathology of depression. The pharmacological blockade or genetic deletion of the NK1 receptor, or the substance P coding gene tac1 led to a decreased emotionality and a reduction of depression-related behaviours in different animal models. In order to characterize molecular changes associated with reduced SP-NK1 signalling in animal models of depression, we assessed the regulation of the CRH system. First, tac1(-/-) animals and tac1(+/+) controls were subjected to bulbectomy, which induces physiological and behavioural changes that are relevant to depression. We demonstrate that tac1(-/-) animals, in contrast to tac1(+/+) controls, do not show anhedonia in the saccharine preference test after bulbectomy. Next, we studied expression levels of CRH, the receptors CRHR1 and CRHR2, and the binding protein CRHBP in the cortex and paraventricular nucleus using real-time RT-PCR. Our results show a strong induction of CRH, CRHBP and CRHR1 expression in the cortex of tac1(-/-), but not in tac1(+/+) animals. In the PVN, bulbectomized tac1(-/-) mice showed an elevated expression of CRHR1 and CRHR2. These results show that substance P/NKA is involved in modulating CRH signalling in an animal model of depression. (C) 2010 Elsevier B.V. All rights reserved.

Frequencies and durations of blooms of cyanobacteria are increasing. Some cyanobacteria can produce cyanotoxins including microcystins (MCs). MCs are the most common toxic products of hazardous algal blooms (HABs), with the greatest potential for exposure and to cause toxicity. Recently, MCs have been shown to disrupt endocrine functions. In this study, for the first time, effects of MC-LR on the hypothalamic-pituitary-inter-renal (HPI) axis during early embryonic development (embryos/larvae) of zebrafish (Danio rerio), were investigated. Embryos/larvae of zebrafish were exposed to 1, 10, 100, or 30014 MC-LR/L during the period of 4-168 h post-fertilization (hpf). Exposure to 300 mu g MC-LR/L resulted in significantly greater concentrations of whole-body cortisol than those in controls. Expressions of genes along the HPI axis and mineralocorticoid receptor (MR-) and glucocorticoid receptor (GR-) centered gene networks were evaluated by use of quantitative real-time PCR Expression of mRNA for crh was significantly down-regulated by exposure to 300 mu g MC-LR/L, while expressions of crhbp, crhr1, and crhr2 were significantly up-regulated, relative to controls. MC-LR caused significantly lesser levels of mRNA for steroidogenic genes including hmgra, star, and cyp17, but expression of mRNA for hsd20b was significantly greater than that of controls. Treatment with MC-LR also altered profiles of transcription of MR- and GR-centered gene networks, which might result in multiple responses. Taken together, these results demonstrated that MC-LR affected the corticosteroid-endocrine system of larvae of zebrafish. This study provided valuable insights into molecular mechanisms behind potential toxicity and endocrine disruption of MCs. (C) 2018 Elsevier Ltd. All rights reserved.