0000000000390458
AUTHOR
Tanja Jene
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,…
Temporal profiling of an acute stress-induced behavioral phenotype in mice and role of hippocampal DRR1.
Abstract Understanding the neurobiological mechanisms underlying the response to an acute stressor may provide novel insights into successful stress-coping strategies. Acute behavioral stress-effects may be restricted to a specific time window early after stress-induction. However, existing behavioral test batteries typically span multiple days or even weeks, limiting the feasibility for a broad behavioral analysis following acute stress. Here, we designed a novel comprehensive behavioral test battery in male mice that assesses multiple behavioral dimensions within a sufficiently brief time window to capture acute stress-effects and its temporal profile. Using this battery, we investigated …
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…
In search for predictive biomarkers: dissecting the molecular pathways in brain and blood underlying poor and good antidepressant treatment response
Major depression poses a serious social and economic threat to modern societies, as it accounts for more lost productivity compared with any other disorder. There are currently two major problems calling for innovative research approaches: 1. The absence of biomarkers predicting antidepressant response and 2. The lack of conceptually novel antidepressant compounds. Identification of biomarkers could allow patient stratification and enable the selection of pathophysiologically distinct patient subgroups to allow optimized treatment choices based on biology. In search for conceptually novel antidepressants, the hippocampal dentate gyrus is a region of particular interest, as there is a large …
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…