Do different types of stress differentially alter behavioural and neurobiological outcomes associated with depression in rodent models? A systematic review

Cataloguing the effects of different types of stress on behaviour and physiology in rodent models has not been comprehensively attempted. Here, we systematically review whether chronic exposure to physical stress, psychosocial stress, or both types of stress can induce different behavioural and neurobiological outcomes in male and female rodents. We found that physical stress consistently increased depressive-like behaviour, impaired social interaction and decreased body weight, while psychosocial stress consistently increased both anxiety- and depressive-like behaviour, impaired social interaction and learning and memory, increased HPA axis activity, peripheral inflammation and microglial activation, and decreased hippocampal neurogenesis in male rodents. Moreover, we found that the combined effect of both stress types resulted in a more severe pathological state defined by increased anxiety- and depressive-like behaviour, impaired social interaction and learning and memory, increased HPA axis activity and central inflammation, and reduced hippocampal neurogenesis and neural plasticity in male rodents. Phenotypes for females were less consistent, irrespective of the type of stress exposure, on account of the limited number of studies using females. This review highlights that the type of stress may indeed matter and will help animal researchers to more appropriately choose a stress/depression model that fits their research purposes.     

Research on the Pathological Mechanism and Drug Treatment Mechanism of Depression

Depression is one of the prevalent and persistent psychiatric illnesses. It brings heavy socioeconomic burden such as healthcare expenditures and even higher suicide rates. Despite many hypotheses about its mechanism have been put forward, so far it is still unclear, not to mention the precise and effective diagnostic or therapeutic methods. In this paper, the current conditions of pathological and pharmacological mechanism of depression were reviewed systematically. Firstly, the most recent hypotheses and metabolomics based research including hereditary, neurotransmitter systems, brain derived neurotrophic factor (BDNF), hyperactivity of the hypothalamic pituitary adrenal (HPA) axis and inflammatory as well as metabolomics were summarized. Secondly, the present situation and development on antidepressant drugs at home and abroad were reviewed. Finally, a conclusion and prospect on the pathological and pharmacological mechanism of depression were provided primarily.     

Hypothalamic insulin and glucagon-like peptide-1 levels in an animal model of depression and their effect on corticotropin-releasing hormone promoter gene activity in a hypothalamic cell line

Background

In depression, excessive glucocorticoid action may cause maladaptive brain changes, including in the pathways controlling energy metabolism. Insulin and glucagon-like peptide-1 (GLP-1), besides regulation of glucose homeostasis, also possess neurotrophic properties. Current study was aimed at investigating the influence of prenatal stress (PS) on insulin, GLP-1 and their receptor (IR and GLP-1R) levels in the hypothalamus. GLP-1 and GLP-1R were assayed also in the hippocampus and frontal cortex – brain regions mainly affected in depression. The second objective was to determine the influence of exendin-4 and insulin on CRH promoter gene activity in in vitro conditions.

Prise en charge des grossesses à risque dans un contexte d’incompatibilité fœto-maternelle plaquettaire et/ou d’allo-immunisation : avis du groupe d’experts du GFHT (Groupe français d’études sur l’hémostase et la thrombose)

IntroductionFetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially devastating disease, seen in 1/800–1000 neonates. FNAIT is the most common cause of early-onset isolated severe neonatal thrombocytopenia in maternity wards. A working group on fetomaternal platelet alloimmunization was created in 2017, under the auspices on the French Group of Thrombosis and Hemostasis (GFHT).ObjectivesThe objective was to survey clinical practices for management of high-risk pregnancies in a context of suspected or confirmed FNAIT.MethodsRecommendations published by the ICTMG were translated in French, and discussed (Fetal and neonatal alloimmune thrombocytopenia: recommendations for evidence-based practice, an international approach. British J of Haematology, 2019, 185, 549–562).ResultsThe study involved centers from France, Switzerland and Belgium: Angers, Besançon, Bordeaux, Brest, Créteil/Clamart, Genève, Grenoble, Liège, Lille, Lyon, Marseille, Nantes, Nîmes, Paris (hôpitaux Necker, Robert Debré et Trousseau), Poitiers, Rennes, Saint-Etienne, Strasbourg, Toulouse, Tours.ConclusionsExpert opinion was validated on September 23, 2020 (consensus ≥ 90%).     

柴越汤对抑郁症大鼠HPA轴的调节作用

目的:探讨柴越汤对慢性应激抑郁模型大鼠下丘脑-垂体-肾上腺(HPA)轴的作用及可能的机制,为临床用药提供理论依据。方法:将筛选合格的60只雄性Wistar大鼠适应性饲养1周后,随机分成正常组、抑郁模型组、阳性组、中药治疗组(包括柴越汤组、小柴胡汤组和越鞠丸组)。除正常组外,其余各组接受孤养结合慢性轻度不可预见性不同应激源的刺激21d制备抑郁模型。造模后按临床等效剂量给予药物干预,持续给药21 d,给药期间,各造模组大鼠均继续给与刺激。通过体重变化、糖水消耗和敞箱实验进行行为学评价,海马组织形态学变化、大鼠血浆促肾上腺皮质激素(ACTH),皮质酮(CORT)的变化,脑内海马糖皮质激素受体(GR)和盐皮质激素受体(MR)蛋白表达的变化,探讨柴越汤的抗抑郁作用机制。结果:与模型组比较,各给药组均可显著提高大鼠体重、增加大鼠糖水消耗比率和行为学得分(P0.05),逆转抑郁模型大鼠过高的血浆ACTH和CORT水平,上调大鼠的海马GR蛋白的表达,而对MR蛋白无影响,在中药组中以柴越汤效果更好。结论:柴越汤对抑郁症具有良好的疗效,拆方后小柴胡汤组、越鞠丸治疗抑郁症疗效较柴越汤略有下降。其作用机制可能通过增强海马GR蛋白的表达,降低血浆ACTH含量和血清CORT含量而起到抗抑郁作用。     

Suckling and Salsolinol Attenuate Responsiveness of the Hypothalamic‐Pituitary‐Adrenal Axis to Stress: Focus on Catecholamines,Corticotrophin‐Releasing Hormone,Adrenocorticotrophic Hormone,Cortisol and Prolactin Secretion in Lactating Sheep

In mammals, the responsiveness of the hypothalamic‐pituitary‐adrenal (HPA) axis to stress is reduced during lactation and this mainly results from suckling by the offspring. The suckling stimulus causes a release of the hypothalamic 1‐metyl‐6,7‐dihydroxy‐1,2,3,4‐tetrahydroisoquinoline (salsolinol) (a derivative of dopamine), one of the prolactin‐releasing factors. To investigate the involvement of salsolinol in the mechanism suppressing stress‐induced HPA axis activity, we conducted a series of experiments on lactating sheep, in which they were treated with two kinds of isolation stress (isolation from the flock with lamb present or absent), combined with suckling and/or i.c.v infusion of salsolinol and 1‐methyl‐3,4‐dihydro‐isoqinoline (1‐MeDIQ; an antagonistic analogue of salsolinol). Additionally, a push–pull perfusion of the infundibular nucleus/median eminence (IN/ME) and blood sample collection with 10‐min intervals were performed during the experiments. Concentrations of perfusate corticotrophin‐releasing hormone (CRH) and catecholamines (noradrenaline, dopamine and salsolinol), as well as concentrations of plasma adenocorticotrophic hormone (ACTH), cortisol and prolactin, were assayed. A significant increase in perfusate noradrenaline, plasma ACTH and cortisol occurred in response to both kinds of isolation stress. Suckling and salsolinol reduced the stress‐induced increase in plasma ACTH and cortisol concentrations. Salsolinol also significantly reduced the stress‐induced noradrenaline and dopamine release within the IN/ME. Treatment with 1‐MeDIQ under the stress conditions significantly diminished the salsolinol concentration and increased CRH and cortisol concentrations. Stress and salsolinol did not increase the plasma prolactin concentration, in contrast to the suckling stimulus. In conclusion, salsolinol released in nursing sheep may have a suppressing effect on stress‐induced HPA axis activity and peripheral prolactin does not appear to participate in its action.     

Sex differences in circadian timing systems: Implications for disease

Virtually every eukaryotic cell has an endogenous circadian clock and a biological sex. These cell-based clocks have been conceptualized as oscillators whose phase can be reset by internal signals such as hormones, and external cues such as light. The present review highlights the inter-relationship between circadian clocks and sex differences. In mammals, the suprachiasmatic nucleus (SCN) serves as a master clock synchronizing the phase of clocks throughout the body. Gonadal steroid receptors are expressed in almost every site that receives direct SCN input. Here we review sex differences in the circadian timing system in the hypothalamic–pituitary–gonadal axis (HPG), the hypothalamic–adrenal–pituitary (HPA) axis, and sleep–arousal systems. We also point to ways in which disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease. Understanding sex differentiated circadian timing systems can lead to improved treatment strategies for these conditions.     

Cortisol Level Modulated by Integrative Meditation in a Dose‐dependent Fashion

Prior research has shown that an additional training session immediately after acute stress decreases release of salivary cortisol in a college student group trained with 5‐day integrative body–mind training (IBMT) in comparison with a control group given the same amount of relaxation training. However, 5 days of training does not influence the basal secretion of cortisol. The current study seeks to extend this finding and determine whether increasing amounts of IBMT will decrease the basal cortisol level, suggesting reduced stress to daily activities. Thirty‐four Chinese undergraduates were randomly assigned either to 4 weeks of IBMT or a relaxation control. Salivary cortisol levels at baseline before training and the three stages of a stress intervention test (i.e. rest, stress and additional 20‐min practice) after 2 and 4 weeks of training were assessed. The basal cortisol level decreased significantly in the IBMT but not in relaxation group after 2 and 4 weeks of training. An additional IBMT practice session immediately after acute stress produced significantly lower cortisol release for the IBMT group in comparison with relaxation at weeks 2 and 4. The results indicate that IBMT produces a change in the basal endocrine system and larger acute effects as the dose of training increases. Copyright © 2013 John Wiley & Sons, Ltd.     

Day-to-day friends’ victimization,aggression perpetration,and morning cortisol activity in late adolescents

This study investigates bidirectional associations between adolescents’ daily experiences of victimization and aggression perpetration within friendships. We investigated (a) across-day associations between victimization and aggression perpetration; (b) morning cortisol activity as a moderator of cross-day victimization and aggression links; and (c) potential sex differences in these patterns. For 4 consecutive days, 99 adolescents (M_age = 18.06, SD = 1.09, 46 females) reported whether they were victimized by or aggressive toward their friends. On three of these days, adolescents provided three morning saliva samples. Multilevel path analyses showed that across days, victimization and aggression were bidirectionally linked, but only for male adolescents. Additionally, for male adolescents, morning cortisol output (but not morning cortisol increase) moderated the association between victimization and next-day aggression; victimization predicted greater next-day aggression for boys with low, but not high, morning cortisol output. Findings implicate a physiological factor that may modify daily links between victimization and aggression in male adolescent friendships.