A trans-dimensional approach to the behavioral aspects of depression

Bessa, João M.; Mesquita, Ana; Oliveira, Miguel; Pêgo, José M.; Cerqueira, João José; Palha, Joana Almeida; Almeida, Osborne F. X.; Sousa, Nuno

doi:10.3389/neuro.08.001.2009

Cited by 205 publications

(274 citation statements)

References 42 publications

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“…Exposure to stressful conditions induces depressive behavior and memory deficits in both rodents and humans (4)(5)(6)(7)(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.…”

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confidence: 73%

“…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).…”

Section: Deleterious Effects Of Stress On Memory and Mood Are Abrogatmentioning

confidence: 99%

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Tau protein is essential for stress-induced brain pathology

Lopes

Vaz‐Silva

Pinto

et al. 2016

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

127

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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mentioning

confidence: 73%

Section: Deleterious Effects Of Stress On Memory and Mood Are Abrogatmentioning

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.

127

111

View full text Add to dashboard Cite

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“…Finally, Bessa et al (2009a) demonstrated that reduction of adult neurogenesis in rats did not change the effectiveness of several ADs in both FST and sucrose preference test, while their efficacy was blocked in NSF. This observation added to the notion that NSF shows anxiolytic rather than antidepressant properties of investigated drugs (discussed in Bessa et al, 2009a;Bessa et al, 2009b;David et al, 2009). Finally, the prevailing perception in the literature, suggests FST to be a proper test to show neurogenesis-dependence of antidepressant efficacy.…”

Section: Discussionmentioning

confidence: 99%

Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine

Jedynak

Kos

Sandi

et al. 2014

Journal of Psychiatric Research

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a b s t r a c tThe neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression.

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“…Moreover, in our earlier study, no correlations were obtained between anxiety-and depression-related behaviours in WKY [17] , hinting at a probable separation of anxiety-and depression-related symptoms [23] . Core symptoms such as anhedonia and learned helplessness are not specific even in humans [24] .…”

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confidence: 99%

Estrous Cycle Phase-Dependent Changes in Anxiety- and Depression-Like Profiles in the Late Adolescent Wistar-Kyoto Rat

D'Souza

Sadananda²

2017

Ann Neurosci

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Background: Depression often manifests during adolescence when the development and networking of social and emotional brain areas is being influenced by hormones. The Wistar Kyoto (WKY) rat has been proposed as an animal model of adolescent depression with various face, construct, and predictive validities for clinical depression having been established. Purpose: The influence of the estrous cycle on anxiety- and depression-like behaviors in female adolescents may be tested out further using this model. Methods: Female adolescent WKY rats were tested for anxiety- and depression-like behaviors in the elevated plus maze and forced swim test (FST) during different phases of the estrous cycle with inbred, age-, and phase-matched Wistar rats as controls. Results: Wistars in proestrus-estrus demonstrated reduced anxiety levels. WKY also demonstrated increased open arm time and entries and closed arm time, but less than Wistars, and as closed arm entries remained unaffected, it did not translate into a lowering of the anxiety levels. Risk taking and risk assessment behaviors were not affected by estrous phases in WKY, though exploratory behavior was reduced in proestrus-estrus. In Wistars, increased risk taking and decreased risk assessment behaviors were observed during proestrus-estrus. Increased immobility in the FST, indicative of learned helplessness was not influenced by phase in the WKY, which was at variance with Wistars that demonstrated phase-specific differences. Conclusion: Results indicate a masking effect of indicative hormones in this putative model of adolescent depression, with implications for an unravelling of the steroid milieu in predisposed adolescent depression and for taking phase-specific time windows into account for therapeutic interventions.

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A trans-dimensional approach to the behavioral aspects of depression

Cited by 205 publications

References 42 publications

Tau protein is essential for stress-induced brain pathology

Tau protein is essential for stress-induced brain pathology

Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine

Estrous Cycle Phase-Dependent Changes in Anxiety- and Depression-Like Profiles in the Late Adolescent Wistar-Kyoto Rat

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