Plasticity of hippocampal corticosteroid receptors during aging in the rat

Hassan, Ali; Patchev, Vladimir K.; Rosenstiel, Philipp von; Holsboer, Florian; Almeida, Osborne F. X.

doi:10.1096/fasebj.13.1.115

Cited by 49 publications

(27 citation statements)

References 58 publications

(81 reference statements)

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“…In line with this view, studies by Hassan et al (1996Hassan et al ( , 1999 and Almeida et al (2000) showed that corticosterone and dexamethasone given at low dosages can exert opposite effects on hippocampal cell viability. It is yet unclear whether these opposing effects are due to differences in penetration of these two corticosteroids through the blood brain barrier or whether they are due to differences in relative occupation of GR and MR.…”

Section: Functional Impairment Of Central Corticosteroid Receptors CLmentioning

confidence: 76%

The Corticosteroid Receptor Hypothesis of Depression

Holsboer

2000

Neuropsychopharmacology

1,984

1,228

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Clinical EvidenceUntil now, the serendipitous discovery of antidepressants in the 1950s has profoundly inspired hypotheses of the pathogenesis of depression. The well-known pharmacological effects of antidepressants on presynaptic uptake transporters and degradating enzymes (i.e., MAO) of serotonin and norepinephrine has focused research on causality and treatment of depression on the metabolism of functional biogenic amines and the capacity of their respective receptors to alter intracellular signaling pathways that ultimately induce changes in gene activity. Elevated circulating levels of stress hormones among depressives were recognized even before antidepressants were discovered, but these changes were seen as epiphenomena, reflecting the stressful experience of depression, although M. Bleuler (1919) already demonstrated that hormones have diverse psychotropic effects and suggested hormone treatments as potential antidepressants. A vast amount of evidence has accumulated, that reject the view that altered stress hormone secretions in depression are epiphenomenal. During the past decade, several research groups formulated a hypothesis relating aberrant stress hormone dysregulation to causality of depression and submitted that antidepressants may act through normalisation of these HPA changes (

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Section: Functional Impairment Of Central Corticosteroid Receptors CLmentioning

confidence: 76%

The Corticosteroid Receptor Hypothesis of Depression

Holsboer

2000

Neuropsychopharmacology

1,984

1,228

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“…Furthermore, in another experiment, male Wister rats, aged 4-5 mo, were treated with the synthetic glucocorticoid dexamethasone (DEX) for 15 d (daily s.c. injections of 300 μg/kg dissolved in sesame oil containing 0.01% ethanol); control animals received sesame oil (five animals per group). This dose of DEX was used because DEX is hampered in brain penetration as it is a substrate of the multidrug-resistant P-glycoprotein (54,55).…”

Section: Methodsmentioning

confidence: 99%

Tau protein is essential for stress-induced brain pathology

Lopes

Vaz‐Silva

Pinto

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

126

111

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Exposure to chronic stress is frequently accompanied by cognitive and affective disorders in association with neurostructural adaptations. Chronic stress was previously shown to trigger Alzheimer's-like neuropathology, which is characterized by Tau hyperphosphorylation and missorting into dendritic spines followed by memory deficits. Here, we demonstrate that stress-driven hippocampal deficits in wild-type mice are accompanied by synaptic missorting of Tau and enhanced Fyn/GluN2B-driven synaptic signaling. In contrast, mice lacking Tau [Tau knockout (Tau-KO) mice] do not exhibit stress-induced pathological behaviors and atrophy of hippocampal dendrites or deficits of hippocampal connectivity. These findings implicate Tau as an essential mediator of the adverse effects of stress on brain structure and function.Tau | stress | hippocampus | depression | memory deficits T he cytoskeletal protein Tau is implicated in the establishment of Alzheimer's disease (AD) (1) as well as excitotoxicity (1) and, more recently, epilepsy (2, 3). Exposure to stressful conditions induces depressive behavior and memory deficits in both rodents and humans (4-8). Studies in rodents have shown that chronic stress triggers Tau hyperphosphorylation, a key pathogenic mechanism in AD, and results in cognitive and mood deficits (9-13); however, those studies do not provide direct evidence for a role of Tau in stress-evoked brain pathology. Given that Tau plays an important role in regulating neuronal architecture and function through its interaction with various cellular targets (e.g., tubulin and Fyn) (14), we hypothesized that Tau mediates the deleterious actions of stress on brain structure and function.To test the above hypothesis, we compared the impact of chronic unpredictable stress (CUS) (11, 15) in mice carrying a null mutation of the mapt gene [Tau knockout (Tau-KO) mice] (16) with their wild-type (WT) littermates. Three well-characterized behavioral endpoints (cognition, coping styles, and anxiety) that are disrupted by CUS served as the primary assay endpoints; these were complemented with measures of hippocampal structural and functional integrity. The hippocampus is a central component of the neurocircuitries that control these behaviors and displays overt lesions in both stress-and Tau-related pathologies; in the latter, the hippocampus is one of the earliest brain regions to show signs of neurodegeneration (1,4,7,(10)(11)(12)(13)17). ResultsDeleterious Effects of Stress on Memory and Mood Are Abrogated in the Absence of Tau Protein. Cognition, mood, and anxiety are interdependent behavioral domains that exhibit complex interactions (5). Different forms of memory were assessed after exposure of WT and Tau-KO mice to the CUS paradigm; the test battery included the Y-maze, Morris water maze (MWM), and the novel object recognition test (NOR). Anxiety was evaluated using the elevated plus maze (EPM), and coping styles and anhedonia were assessed using the forced swim test (FST) and the sucrose consumption test (SCT).Two-way ANOVA ...

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“…Nonetheless, concerns about its penetrability of the BBB should not be lightly dismissed and should be considered in the context of the species under investigation. For example, whereas dexamethasone is clearly excluded from penetrating the mouse brain through the actions of the multiple drug resistance protein (1a isoform) [53], femtomol concentrations of [3H]-dexamethasone injected intraperitoneally can be autoradiographically visualized in the hippocampus and other GC-concentrating brain regions within 1 h [54].…”

Section: Glucocorticoids Neuronal Atrophy and Neuronal Deathmentioning

confidence: 99%