0000000000390460
AUTHOR
Annika Hasch
Chronic social stress lessens the metabolic effects induced by a high-fat diet
Stress has a major impact on the modulation of metabolism, as previously evidenced by hyperglycemia following chronic social defeat (CSD) stress in mice. Although CSD-triggered metabolic dysregulation might predispose to pre-diabetic conditions, insulin sensitivity remained intact, and obesity did not develop, when animals were fed with a standard diet (SD). Here, we investigated whether a nutritional challenge, a high-fat diet (HFD), aggravates the metabolic phenotype and whether there are particularly sensitive time windows for the negative consequences of HFD exposure. Chronically stressed male mice and controls (CTRL) were kept under (i) SD-conditions, (ii) with HFD commencing post-CSD,…
Chronic social stress-induced hyperglycemia in mice couples individual stress susceptibility to impaired spatial memory
Significance Stress-associated mental disorders and diabetes pose an enormous socio-economic burden. Glucose dysregulation occurs with both psychosocial and metabolic stress. While cognitive impairments are common in metabolic disorders such as diabetes and are accompanied by hyperglycemia, a causal role for glucose has not been established. We show that chronic social defeat (CSD) stress induces lasting peripheral and central hyperglycemia and impaired glucose metabolism in a subgroup of mice. Animals exhibiting hyperglycemia early post-CSD display spatial memory impairments that can be rescued by the antidiabetic empagliflozin. We demonstrate that individual stress vulnerability to glucos…
Longitudinal CSF proteome profiling in mice to uncover the acute and sustained mechanisms of action of rapid acting antidepressant (2R,6R)-hydroxynorketamine (HNK)
Delayed onset of antidepressant action is a shortcoming in depression treatment. Ketamine and its metabolite (2R,6R)-hydroxynorketamine (HNK) have emerged as promising rapid-acting antidepressants. However, their mechanism of action remains unknown. In this study, we first described the anxious and depression-prone inbred mouse strain, DBA/2J, as an animal model to assess the antidepressant-like effects of ketamine and HNK in vivo. To decode the molecular mechanisms mediating HNK's rapid antidepressant effects, a longitudinal cerebrospinal fluid (CSF) proteome profiling of its acute and sustained effects was conducted using an unbiased, hypothesis-free mass spectrometry-based proteomics app…
Rapid acting antidepressant (2R,6R)-hydroxynorketamine (HNK) targets glucocorticoid receptor signaling: a longitudinal cerebrospinal fluid proteome study
AbstractDelayed onset of antidepressant action is a shortcoming in depression treatment. Ketamine and its metabolite (2R,6R)-hydroxynorketamine (HNK) have emerged as promising rapidacting antidepressants. However, their mechanism of action remains unknown. In this study, we first described the anxious and depression-prone inbred mouse strain, DBA/2J, as a animal model to assess the antidepressant-like effects of ketamine and HNK in vivo. To decode the molecular mechanisms mediating HNK’s rapid antidepressant effects, a longitudinal cerebrospinal fluid (CSF) proteome profiling of its acute and sustained effects was conducted using an unbiased, hypothesis-free mass spectrometry-based proteomi…