Chronic stress, hippocampus and parvalbumin-positive interneurons: what do we know so far?

2016 ◽  
Vol 27 (4) ◽  
pp. 397-409 ◽  
Author(s):  
Ivan Zaletel ◽  
Dragana Filipović ◽  
Nela Puškaš
Keyword(s):  
Stress Response ◽  
Mood Disorders ◽  
Chronic Stress ◽  
Hpa Axis ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Emotional Information ◽  
Contextual Memory ◽  
Response To Stress ◽  
Unexplored Area

AbstractThe hippocampus is a brain structure involved in the regulation of hypothalamic-pituitary-adrenal (HPA) axis and stress response. It plays an important role in the formation of declarative, spatial and contextual memory, as well as in the processing of emotional information. As a part of the limbic system, it is a very susceptible structure towards the effects of various stressors. The molecular mechanisms of structural and functional alternations that occur in the hippocampus under chronic stress imply an increased level of circulating glucocorticoids (GCs), which is an HPA axis response to stress. Certain data show that changes induced by chronic stress may be independent from the GCs levels, opening the possibility of existence of other poorly explored mechanisms and pathways through which stressors act. The hippocampal GABAergic parvalbumin-positive (PV+) interneurons represent an especially vulnerable population of neurons in chronic stress, which may be of key importance in the development of mood disorders. However, cellular and molecular hippocampal changes that arise as a consequence of chronic stress still represent a large and unexplored area. This review discusses the current knowledge about the PV+ interneurons of the hippocampus and the influence of chronic stress on this intriguing population of neurons.

Abnormalities in neuroendocrine stress response in psychosis: the role of endocannabinoids

2015 ◽  
Vol 46 (1) ◽  
pp. 27-45 ◽  
Author(s):  
E. Appiah-Kusi ◽  
E. Leyden ◽  
S. Parmar ◽  
V. Mondelli ◽  
P. McGuire ◽  
...  
Keyword(s):  
Stress Response ◽  
Hpa Axis ◽  
Psychotic Disorders ◽  
Endocannabinoid System ◽  
Current Evidence ◽  
Response To Stress ◽  
Health And Disease ◽  
Stress Response System ◽  
Precise Role

The aim of this article is to summarize current evidence regarding alterations in the neuroendocrine stress response system and endocannabinoid system and their relationship in psychotic disorders such as schizophrenia. Exposure to stress is linked to the development of a number of psychiatric disorders including psychosis. However, the precise role of stress in the development of psychosis and the possible mechanisms that might underlie this are not well understood. Recently the cannabinoid hypothesis of schizophrenia has emerged as a potential line of enquiry. Endocannabinoid levels are increased in patients with psychosis compared with healthy volunteers; furthermore, they increase in response to stress, which suggests another potential mechanism for how stress might be a causal factor in the development of psychosis. However, research regarding the links between stress and the endocannabinoid system is in its infancy. Evidence summarized here points to an alteration in the baseline tone and reactivity of the hypothalamic–pituitary–adrenal (HPA) axis as well as in various components of the endocannabinoid system in patients with psychosis. Moreover, the precise nature of the inter-relationship between these two systems is unclear in man, especially their biological relevance in the context of psychosis. Future studies need to simultaneously investigate HPA axis and endocannabinoid alterations both at baseline and following experimental perturbation in healthy individuals and those with psychosis to understand how they interact with each other in health and disease and obtain mechanistic insight as to their relevance to the pathophysiology of schizophrenia.

scholarly journals Acute or chronic stress induce cell compartment-specific phosphorylation of glucocorticoid receptor and alter its transcriptional activity in Wistar rat brain

2009 ◽  
Vol 202 (1) ◽  
pp. 87-97 ◽  
Author(s):  
Miroslav Adzic ◽  
Jelena Djordjevic ◽  
Ana Djordjevic ◽  
Ana Niciforovic ◽  
Constantinos Demonacos ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Chronic Stress ◽  
Hpa Axis ◽  
Transcriptional Activity ◽  
Subcellular Location ◽  
Wistar Rat ◽  
High Serum ◽  
Response To Stress ◽  
Neurotropic Factor ◽  
Hpa Axis Activity

Chronic stress and impaired glucocorticoid receptor (GR) feedback are important factors for the compromised hypothalamic–pituitary–adrenal (HPA) axis activity. We investigated the effects of chronic 21 day isolation of Wistar rats on the extrinsic negative feedback part of HPA axis: hippocampus (HIPPO) and prefrontal cortex (PFC). In addition to serum corticosterone (CORT), we followed GR subcellular localization, GR phosphorylation at serine 232 and serine 246, expression of GR regulated genes: GR, CRF and brain-derived neurotropic factor (BDNF), and activity of c-Jun N-terminal kinase (JNK) and Cdk5 kinases that phosphorylate GR. These parameters were also determined in animals subjected to acute 30 min immobilization, which was taken as ‘normal’ adaptive response to stress. In isolated animals, we found decreased CORT, whereas in animals exposed to acute immobilization, CORT was markedly increased. Even though the GR was predominantly localized in the nucleus of HIPPO and PFC in acute, but not in chronic stress, the expression of GR, CRF, and BDNF genes was similarly regulated under both acute and chronic stresses. Thus, the transcriptional activity of GR under chronic isolation did not seem to be exclusively dependent on high serum CORT levels nor on the subcellular location of the GR protein. Rather, it resulted from the increased Cdk5 activation and phosphorylation of the nuclear GR at serine 232 and the decreased JNK activity reflected in decreased phosphorylation of the nuclear GR at serine 246. Our study suggests that this nuclear isoform of hippocampal and cortical GR may be related to hypocorticism i.e. HPA axis hypoactivity under chronic isolation stress.

scholarly journals Regulation of dopamine system responsivity and its adaptive and pathological response to stress

2015 ◽  
Vol 282 (1805) ◽  
pp. 20142516 ◽  
Author(s):  
Pauline Belujon ◽  
Anthony A. Grace
Keyword(s):  
Stress Response ◽  
Psychiatric Disorders ◽  
Crucial Role ◽  
Current Knowledge ◽  
Pathological Response ◽  
Psychiatric Diseases ◽  
Dopamine System ◽  
Norepinephrine System ◽  
Response To Stress

Although, historically, the norepinephrine system has attracted the majority of attention in the study of the stress response, the dopamine system has also been consistently implicated. It has long been established that stress plays a crucial role in the pathogenesis of psychiatric disorders. However, the neurobiological mechanisms that mediate the stress response and its effect in psychiatric diseases are not well understood. The dopamine system can play distinct roles in stress and psychiatric disorders. It is hypothesized that, even though the dopamine (DA) system forms the basis for a number of psychiatric disorders, the pathology is likely to originate in the afferent structures that are inducing dysregulation of the DA system. This review explores the current knowledge of afferent modulation of the stress/DA circuitry, and presents recent data focusing on the effect of stress on the DA system and its relevance to psychiatric disorders.

scholarly journals Comparison of miRNA expression profiles in pituitary–adrenal axis between Beagle and Chinese Field dogs after chronic stress exposure

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1682 ◽  
Author(s):  
Wei Luo ◽  
Meixia Fang ◽  
Haiping Xu ◽  
Huijie Xing ◽  
Jiangnan Fu ◽  
...  
Keyword(s):  
Stress Response ◽  
Adrenal Cortex ◽  
Chronic Stress ◽  
Hpa Axis ◽  
Mirna Expression ◽  
Target Genes ◽  
Expression Profiles ◽  
Stress Exposure ◽  
Mirna Expression Profiles ◽  
Pituitary Adrenal Axis

MicoRNAs (miRNAs), usually as gene regulators, participate in various biological processes, including stress responses. The hypothalamus–pituitary–adrenal axis (HPA axis) is an important pathway in regulating stress response. Although the mechanism that HPA axis regulates stress response has been basically revealed, the knowledge that miRNAs regulate stress response within HPA axis, still remains poor. The object of this study was to investigate the miRNAs in the pituitary and adrenal cortex that regulate chronic stress response with high-throughput sequencing. The pituitary and adrenal cortex of beagles and Chinese Field dogs (CFD) from a stress exposure group (including beagle pituitary 1 (BP1), CFD pituitary 1 (CFDP1), beagle adrenal cortex 1 (BAC1), CFD adrenal cortex 1 (CFDAC1)) and a control group (including beagle pituitary 2 (BP2), CFD pituitary 2 (CFDP2), beagle adrenal cortex 2 (BAC2), CFD adrenal cortex 2 (CFDAC2)), were selected for miRNA-seq comparisons. Comparisons, that were made in pituitary (including BP1 vs. BP2, CFDP1 vs. CFDP2, BP1 vs. CFDP1 and BP2 vs. CFDP2) and adrenal cortex (including BAC1 vs. BAC2, CFDAC1 vs. CFDAC2, BAC1 vs. CFDAC1 and BAC2 vs. CFDAC2), showed that a total of 39 and 18 common differentially expressed miRNAs (DE-miRNAs) (Total read counts > 1,000, Fold change > 2 &p-value < 0.001), that shared in at least two pituitary comparisons and at least two adrenal cortex comparisons, were detected separately. These identified DE-miRNAs were predicted for target genes, thus resulting in 3,959 and 4,010 target genes in pituitary and adrenal cortex, respectively. Further, 105 and 10 differentially expressed genes (DEGs) (Fold change > 2 &p-value < 0.05) from those target genes in pituitary and adrenal cortex were obtained separately, in combination with our previous corresponding transcriptome study. Meanwhile, in line with that miRNAs usually negatively regulated their target genes and the dual luciferase reporter assay, we finally identified cfa-miR-205 might play an important role by upregulatingMMDin pituitary and hippocampus, thus enhancing the immune response, under chronic stress exposure. Our results shed light on the miRNA expression profiles in the pituitary and adrenal cortex with and without chronic stress exposure, and provide a new insight into miR-205 with its feasible role in regulating chronic stress in the pituitary and hippocampus through targetingMMD.

scholarly journals Effects of L-3,4-dihydroxyphenylalanine (L-Dopa) Treatment in the Neuroendocrine Response to Stress

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A67-A68
Author(s):  
Santiago Jordi Orrillo ◽  
Mercedes Imsen ◽  
Alfonsina Lizarraga ◽  
Ana Clara Romero ◽  
Fernanda De Fino ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Stress Response ◽  
Hpa Axis ◽  
Sympathetic Nerves ◽  
Serum Levels ◽  
Male Wistar Rats ◽  
Response To Stress ◽  
Behavioural Tests ◽  
Hpa Axis Activity

Abstract Stressful stimuli evoke a complex response mediated by two systems: the Sympathetic-Adreno-Medullar (SAM) axis and the Hypothalamus-Pituitary-Adrenal (HPA) axis. Among the factors involved in stress, glucocorticoids and catecholamines secreted from the adrenal glands and sympathetic nerves are the main effectors of the physiological adaptations to stressors. Besides these, prolactin (PRL) is another hormone secreted under stress conditions. Catecholamines are synthesized from the hydroxylated precursor L-Dopa. This agent is commonly used for the treatment of Parkinson’s disease and it would act as a neurotransmitter per se. On the other hand, it has been suggested that HPA axis dysregulation is a potential risk factor for the development of depression. In line with this, several studies reported that L-Dopa treatment may alter the serum levels of ACTH, PRL, and glucocorticoids in parkinsonian patients and Parkinson’s disease animal models. In the present study, we determined whether the chronic treatment with L-Dopa altered the stress response inducing depressive-like behaviours. Adult male Wistar rats were treated orally during 24 days with LEBOCAR® - commercial formulation of L-Dopa (75 mg/day) and Carbidopa (7.5 mg/day) - in drinking water. Animals were stressed by immobilization during the last 9 days of treatment and depressive-like behaviours were assessed by the sucrose intake and forced swimming tests. Behavioural tests showed no signs of depressive-like behaviours in the LEBOCAR®-treated and/or stressed rats. We next explored the SAM axis reactivity. Circulating noradrenaline and adrenaline increased in rats treated with LEBOCAR® (p&lt;0.05; HPLC). Also, the adrenals from stressed animals showed higher content of adrenaline (p&lt;0.05). Then, we studied the HPA axis activity. Chronically stressed rats displayed a lower ACTH secretion (ELISA) and a downregulation of POMC expression (qPCR) in the anterior pituitary (p&lt;0.05). In addition, LEBOCAR® treatment induced a reduction in serum ACTH and POMC levels (p&lt;0.05). As expected, serum corticosterone (ELISA) enhanced under chronic stress, an effect that was inhibited by treatment with LEBOCAR® (p&lt;0.05). Finally, pituitary PRL gene expression (qPCR) was downregulated by LEBOCAR® treatment with a more pronounced effect when rats were also stressed (p&lt;0.05). Our results suggest that L-Dopa alters the neuroendocrine stress response enhancing SAM axis reactivity and reducing HPA axis activity and PRL expression.

scholarly journals Sexual Dimorphism in Glucocorticoid Stress Response

2021 ◽  
Vol 22 (6) ◽  
pp. 3139
Author(s):  
Marie-Pierre Moisan
Keyword(s):  
Sexual Dimorphism ◽  
Stress Response ◽  
Chronic Stress ◽  
Molecular Mechanisms ◽  
Gonadal Hormones ◽  
Gender Effects ◽  
Sex Bias ◽  
Prenatal Period ◽  
Glucocorticoid Hormones ◽  
Specific Manner

Chronic stress is encountered in our everyday life and is thought to contribute to a number of diseases. Many of these stress-related disorders display a sex bias. Because glucocorticoid hormones are the main biological mediator of chronic stress, researchers have been interested in understanding the sexual dimorphism in glucocorticoid stress response to better explain the sex bias in stress-related diseases. Although not yet demonstrated for glucocorticoid regulation, sex chromosomes do influence sex-specific biology as soon as conception. Then a transient rise in testosterone start to shape the male brain during the prenatal period differently to the female brain. These organizational effects are completed just before puberty. The cerebral regions implicated in glucocorticoid regulation at rest and after stress are thereby impacted in a sex-specific manner. After puberty, the high levels of all gonadal hormones will interact with glucocorticoid hormones in specific crosstalk through their respective nuclear receptors. In addition, stress occurring early in life, in particular during the prenatal period and in adolescence will prime in the long-term glucocorticoid stress response through epigenetic mechanisms, again in a sex-specific manner. Altogether, various molecular mechanisms explain sex-specific glucocorticoid stress responses that do not exclude important gender effects in humans.

Blunted HPA Axis Response to Stress Influences Susceptibility to Posttraumatic Stress Response in Rats

2006 ◽  
Vol 59 (12) ◽  
pp. 1208-1218 ◽  
Author(s):  
Hagit Cohen ◽  
Joseph Zohar ◽  
Yori Gidron ◽  
Michael A. Matar ◽  
Dana Belkind ◽  
...  
Keyword(s):  
Stress Response ◽  
Posttraumatic Stress ◽  
Hpa Axis ◽  
Response To Stress ◽  
Stress Influences ◽  
Posttraumatic Stress Response

The HPA and immune axes in stress: the involvement of the serotonergic system

2005 ◽  
Vol 20 (S3) ◽  
pp. S302-S306 ◽  
Author(s):  
B.E. Leonard
Keyword(s):  
Stress Response ◽  
Chronic Stress ◽  
Hpa Axis ◽  
Feedback Inhibition ◽  
Critical Role ◽  
Serotonergic System ◽  
Anxiety And Depression ◽  
Acute And Chronic Stress ◽  
The Impact ◽  
The Brain

AbstractThe impact of acute and chronic stress on the hypothalamic-pituitary-adrenal (HPA) axis is reviewed and evidence presented that corticotrophin releasing factor (CRF) is the stress neurotransmitter which plays an important role in the activation of the central sympathetic and serotonergic systems. The activity of CRF is expressed through specific receptors (CRF 1 and 2) that are antagonistic in their actions and widely distributed in the limbic regions of the brain, as well as in the hypothalamus, and on immune cells.The mechanism whereby chronic stress, via the CRF induced activation of the dorsal raphe nucleus, can induce a change in the serotonergic system, involves an increase in the 5HT2A and a decrease in the 5HT1A receptor mediated function. Such changes contribute to the onset of anxiety and depression. In addition, the hypersecretion of glucocorticoids that is associated with chronic stress and depression desensitises the central glucocorticoid receptors to the negative feedback inhibition of the HPA axis. This indirectly results in the further activation of the HPA axis.The rise in pro-inflammatory cytokines that usually accompanies the chronic stress response results in a further stimulation of the HPA axis thereby adding to the stress response. While CRF would appear to play a pivotal role, evidence is provided that simultaneous changes in the serotonergic and noradrenergic systems, combined with the activation of peripheral and central macrophages that increase the pro-inflammatory cytokine concentrations in the brain and blood, also play a critical role in predisposing to anxiety and depression. Neurodegenerative changes in the brain that frequently occur in the elderly patient with major depression, could result from the activation of indoleaminedioxygenase (IDO), a widely distributed enzyme that converts tryptophan via the kynenine pathway to for the neurotoxic end product quinolinic acid.

scholarly journals The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress

2006 ◽  
Vol 8 (4) ◽  
pp. 383-395 ◽  
Keyword(s):  
Stress Response ◽  
Brain Stem ◽  
Hpa Axis ◽  
Feedback Inhibition ◽  
Adaptive Responses ◽  
Hypothalamic Pituitary Adrenal ◽  
Afferent Projections ◽  
The Face ◽  
Response To Stress

Animals respond to stress by activating a wide array of behavioral and physiological responses that are collectively referred to as the stress response. Corticotropin-releasing factor (CRF) plays a central role in the stress response by regulating the hypothalamic-pituitary-adrenal (HPA) axis. In response to stress, CRF initiates a cascade of events that culminate in the release of glucocorticoids from the adrenal cortex. As a result of the great number of physiological and behavioral effects exerted by glucocorticoids, several mechanisms have evolved to control HPA axis activation and integrate the stress response. Glucocorticoid feedback inhibition plays a prominent role in regulating the magnitude and duration of glucocorticoid release. In addition to glucocorticoid feedback, the HPA axis is regulated at the level of the hypothalamus by a diverse group of afferent projections from limbic, midbrain, and brain stem nuclei. The stress response is also mediated in part by brain stem noradrenergic neurons, sympathetic andrenomedullary circuits, and parasympathetic systems. In summary, the aim of this review is to discuss the role of the HPA axis in the integration of adaptive responses to stress. We also identify and briefly describe the major neuronal and endocrine systems that contribute to the regulation of the HPA axis and the maintenance of homeostasis in the face of aversive stimuli.

scholarly journals Influences of Stress and Sex on the Paraventricular Thalamus: Implications for Motivated Behavior

2021 ◽  
Vol 15 ◽  
Author(s):  
Sydney A. Rowson ◽  
Kristen E. Pleil
Keyword(s):  
Chronic Stress ◽  
Hpa Axis ◽  
Reciprocal Relationship ◽  
Stress Exposure ◽  
Acute And Chronic Stress ◽  
Motivated Behavior ◽  
Neuroendocrine Response ◽  
Response To Stress ◽  
Motivated Behaviors

The paraventricular nucleus of the thalamus (PVT) is a critical neural hub for the regulation of a variety of motivated behaviors, integrating stress and reward information from environmental stimuli to guide discrete behaviors via several limbic projections. Neurons in the PVT are activated by acute and chronic stressors, however several roles of the PVT in behavior modulation emerge only following repeated stress exposure, pointing to a role for hypothalamic pituitary adrenal (HPA) axis modulation of PVT function. Further, there may be a reciprocal relationship between the PVT and HPA axis in which chronic stress-induced recruitment of the PVT elicits an additional role for the PVT to regulate motivated behavior by modulating HPA physiology and thus the neuroendocrine response to stress itself. This complex interaction may make the PVT and its role in influencing motivated behavior particularly susceptible to chronic stress-induced plasticity in the PVT, especially in females who display increased susceptibility to stress-induced maladaptive behaviors associated with neuropsychiatric diseases. Though literature is describing the sex-specific effects of acute and chronic stress exposure on HPA axis activation and motivated behaviors, the impact of sex on the role of the PVT in modulating the behavioral and neuroendocrine response to stress is less well established. Here, we review what is currently known regarding the acute and chronic stress-induced activation and behavioral role of the PVT in male and female rodents. We further explore stress hormone and neuropeptide signaling mechanisms by which the HPA axis and PVT interact and discuss the implications for sex-dependent effects of chronic stress on the PVT’s role in motivated behaviors.

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