Chronic low dose corticosterone exposure decreased hippocampal cell proliferation, volume and induced anxiety and depression like behaviours in mice

Murray, Fraser; Smith, David; Hutson, Peter H.

doi:10.1016/j.ejphar.2008.01.014

Cited by 294 publications

(201 citation statements)

References 57 publications

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“…In rodents, adult neurogenesis is a key mechanism to maintain plasticity in response to both internal and environmental challenges , and its functional relevance ranges from perceptive to cognitive functions, including mood regulation, pattern separation, learning, memory, and behavioral responses to olfactory cues (Breton-Provencher et al, 2009;Lazarini and Lledo, 2011;Alonso et al, 2012). Abnormal hippocampal neurogenesis is likely to participate in psychiatric disorders, such as depression (Sahay and Hen, 2007), and the production of adult-born hippocampal neurons is influenced by stress and glucocorticoids (Murray et al, 2008;David et al, 2009;Snyder et al, 2011). In MDD patients and mouse models of chronic stress, there is evidence for reduced hippocampal volume and impaired adult neurogenesis, both of which can be restored by antidepressant treatments (Campbell et al, 2004;Boldrini et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Anxiety- and Depression-Like States Lead to Pronounced Olfactory Deficits and Impaired Adult Neurogenesis in Mice

et al. 2016

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Numerous clinical reports underscore the frequency of olfactory impairments in patients suffering from major depressive disorders (MDDs), yet the underlying physiopathological mechanisms remain poorly understood. We hypothesized that one key link between olfactory deficits and MDD lies in hypercortisolemia, a cardinal symptom of MDD. Corticosterone (CORT) is known to negatively correlate with hippocampal neurogenesis, yet its effects on olfactory neurogenesis and olfaction remain unknown. Here we used a rodent model of anxiety/depression-like states, which is based on chronic CORT administration and studied the effects of the antidepressant fluoxetine (FLX) on behavior, olfaction, and adult neurogenesis in the dentate gyrus (DG), olfactory bulb (OB), and the olfactory epithelium (OE). Chronic CORT had no effect on cell proliferation in the OE or on olfactory sensory neurons projecting to the OB, but induced pronounced deficits in olfactory acuity, fine discrimination of odorants and olfactory memory. These alterations were accompanied by a significant decrease in the number of adult-born neurons in both the DG and OB. Remarkably, FLX not only reversed depression-like states as expected, but also improved olfactory acuity, memory, and restored impaired adult neurogenesis. However, fine olfactory discrimination was not restored. Morphological analysis of adult-born neurons in both the DG and the OB showed that dendritic complexity was not significantly affected by CORT, but was increased by FLX. These findings demonstrate an essential role for glucocorticoids in triggering olfactory impairments in MDD and highlight a novel therapeutic effect of FLX.

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Section: Introductionmentioning

confidence: 99%

Anxiety- and Depression-Like States Lead to Pronounced Olfactory Deficits and Impaired Adult Neurogenesis in Mice

et al. 2016

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“…Long-term exposure of corticosteroids is associated with a range of actions leading to depressive behaviour [47,48]. Changes in the hippocampus of the brain caused by the extended use of corticosteroids [49][50][51] could be attributed to depressive behaviour. The decrease in sucrose preference can be a manifestation of behavioural changes like anhedonia, seen with chronic use of corticosteroids as documented in previous research [52].…”

Section: Discussionmentioning

confidence: 99%

Role of Aspirin and Dexamethasone against Experimentally Induced Depression in Rats

Bhatt

Shukla

Raval

et al. 2016

Basic Clin Pharma Tox

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A large number of current studies indicate that inflammatory mediators may contribute to depression in experimental models as well as in human beings. Nevertheless, the subject, whether anti-inflammatory treatments can prevent depression still remains controversial. In the present study, a chronic mild stress (CMS) model of male Sprague Dawley rats was used to investigate the role of anti-inflammatory drugs in the treatment of depression. All the animals in different groups, except the normal control group, were exposed to CMS procedure for 28 days and concurrently treated with aspirin (10 mg/kg, p.o.), dexamethasone (1 mg/kg p.o.) and amitriptyline (10 mg/kg p.o., reference standard), respectively. Amitriptyline was also used in combination with aspirin and dexamethasone to inspect any synergistic effects. Tests performed towards the end of the study included sucrose preference test, behavioural tests like forced swim test, elevated plus-maze, light/dark box, locomotor activity and biochemical estimations like serum cortisol and brain neurotransmitters. Disease control group (CMS-treated) produced significant depressive behaviour in rats. The animals treated with aspirin showed increased sucrose preference, decreased immobility time in forced swim test, decreased serum cortisol and increased brain serotonin levels signifying antidepressant action. In contrast, there was aggravation of depressive behaviour in rats treated with dexamethasone. Together, these findings suggest that aspirin can serve as a potential antidepressant both individually and as adjunctive agent in the treatment of depression. Inhibition of the inflammatory mediators during stress procedures or any other potential physiological and biochemical mechanisms may be involved in its antidepressant effect.Major depression is one of the most commonly diagnosed neuropsychiatric disorders, with a worldwide life-time prevalence of 17%. It is estimated that by 2020, major depression will be the second most disabling condition in the world. Despite considerable strides have been made over the years, treatment-resistant depression (TRD) remains a common condition which accounts for approximately 30% of the depressed population [1,2]. Historically, treatment options for depression and associated disorders have focused on the medications that modify the activity of monoamine neurotransmitter systems [3].Several studies support the role of inflammation and immune system deregulation in pathophysiology of depression [4,5]. Patients with major depression have been found to exhibit all of the vital features of inflammation, including elevation of inflammatory cytokines, acute phase proteins, chemokines, adhesion molecules and inflammatory mediators such as prostaglandins. Repeated administration of IL-1, TNF-a and IL-6 elicits depressive-like behaviour in animals [6][7][8]. The mechanisms contributing to pathogenesis of depression incorporate abnormal neurotransmitter metabolism, altered neuro-endocrine functions and distorted neural plasticity [9,10...

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“…It has been shown that corticosterone injections repeated for 21 days increased the percentage of immobility time and decreased the percentage of swimming time in a forced swim test; those two effects being commonly regarded as a depression-like behavior in rats [31]. A specific advantage of this model is the elimination of the adaptation of the organism to a repeated stressor [64,65,77]. An earlier study from this laboratory showed that repeated corticosterone administration caused changes in the reactivity of 5-HT 1A and 5-HT 4 receptors in the CA1 area of the hippocampus, which were reversed by a simultaneous treatment with imipramine [108].…”

Section: +mentioning

confidence: 99%

“…A chronic high level of corticosteroid hormones (cortisol in humans and corticosterone in rodents) leads to hyperactivity [77], deregulation of the functions of the hypothalamus-pituitary-adrenal (HPA) axis and disrupts the mechanism of the HPA axis negative feedback [64,87]. Since a prolonged elevation of plasma cortisol level often occurs in the course of depressive disorders in human patients, it has been commonly accepted that long-lasting alterations in the activity of the HPA axis are a risk factor to the precipitation of the disease [71].…”

Section: +mentioning

confidence: 99%

Stress- and antidepressant treatment-induced modifications of 5-HT7 receptor functions in the rat brain

Tokarski

Bobula

Grzegorzewska-Hiczwa

et al. 2012

Pharmacological Reports

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Abstract:This paper summarizes a series of electrophysiological studies aimed at finding the effects of the activation of 5-HT 7 receptors on neuronal excitability as well as on excitatory and inhibitory synaptic transmission in the hippocampus and in the frontal cortex of the rat. These studies demonstrated that 5-HT 7 receptors play an important role in the modulation of the activity of the hippocampal network by regulating the excitability of pyramidal cells of the CA1 area, as well as via their effect on GABA and glutamatergic transmission. The reactivity of 5-HT 7 receptors in the hippocampus is decreased by repeated administration of antidepressant drugs and increased by a prolonged high level of corticosterone. More importantly, administration of antidepressant drug, imipramine, prevents the occurrence of corticosterone-induced changes in the function of hippocampal 5-HT 7 receptors. It has also been found that the blockade of 5-HT 7 receptors by the selective antagonist SB 269970, lasting for a few days, causes similar changes to those observed after long-term administration of antidepressants. Thus, it seems that the pharmacological blockade of 5-HT 7 receptors produces faster effects compared to classic antidepressant drugs. A similarity between the changes in the glutamatergic transmission induced by the blockade of 5 HT 7 receptors and those caused by repeated administration of the antidepressant drug, imipramine, has also been found in the frontal cortex. It has also been shown that the changes in glutamatergic transmission and the impairment of long-term synaptic plasticity in the frontal cortex of animals subjected to repeated restraint stress are reversed by the blockade of 5-HT 7 receptors. Overall, these studies, together with the data provided by other investigators, support the hypothesis that 5-HT 7 receptor antagonists may become a prototype of a new class of antidepressant drugs. Such compounds will not function by blocking 5-HT reuptake, as many of the currently used drugs, but through a direct interaction with the 5-HT 7 receptor. This type of action is highly selective and usually does not require the occurrence of adaptive changes in neuronal functions, thus allowing for a much quicker therapeutic effect.

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Chronic low dose corticosterone exposure decreased hippocampal cell proliferation, volume and induced anxiety and depression like behaviours in mice

Cited by 294 publications

References 57 publications

Anxiety- and Depression-Like States Lead to Pronounced Olfactory Deficits and Impaired Adult Neurogenesis in Mice

Anxiety- and Depression-Like States Lead to Pronounced Olfactory Deficits and Impaired Adult Neurogenesis in Mice

Role of Aspirin and Dexamethasone against Experimentally Induced Depression in Rats

Stress- and antidepressant treatment-induced modifications of 5-HT7 receptor functions in the rat brain

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