Differential impact of chronic stress along the hippocampal dorsal–ventral axis

Pinto, Vítor; Costa, José Carlos; Morgado, Pedro; Mota, Cristina; Miranda, André; Bravo, Francisca Vaz; Oliveira, Tiago Gil; Cerqueira, João José; Sousa, Nuno

doi:10.1007/s00429-014-0713-0

Cited by 62 publications

(65 citation statements)

References 41 publications

(64 reference statements)

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“…As previously described (Bessa et al, 2009a;Pinto et al, 2014), uCMS-exposed animals presented significantly shorter granule neurons in the dDG compared with CT animals (t 8 ¼ 4.560, p ¼ 0.0019, d ¼ 0.7221; Figure 2a). All ADs, excluding agomelatine, reversed this structural change up to the levels of CT (F (4,21) ¼ 5.344, p ¼ 0.0040, Z 2 ¼ 0.5054; Figure 2a).…”

Section: Neuroplastic Changes In the Hippocampal Dgsupporting

confidence: 81%

“…Given the evidence for a heterogeneous structure and function along the septotemporal axis of the DG (Kheirbek et al, 2013;Tanti and Belzung, 2013), with the dDG contributing mainly to functions related to learning and memory, whereas the vDG is more related to anxiety and emotional regulation (Tanti and Belzung 2013), we would expect also an impact on the vDG. Moreover, while previous reports have shown that the effects of some AD treatments on adult hippocampal neurogenesis are region specific along the septo-temporal axis of the hippocampus, the implication of morphological changes in granule neurons has not been fully elucidated (Felice et al, 2012;O'Leary et al, 2012), even though a contrasting gradient of stress-induced morphological and physiological changes along the septo-temporal axis of the hippocampus has been shown (Pinto et al, 2014).…”

Section: Discussionmentioning

confidence: 97%

“…For each animal, at least eight neurons fulfilling previously described criteria (Pinto et al, 2014) were analyzed in the dorsal and ventral hippocampal DG. For each selected neuron, dendritic branches were reconstructed at Â 1000 (oil) magnification using a motorized microscope (Axioplan 2; Carl Zeiss, LLC, United States) and the Neurolucida software (MBF Bioscience, Williston, VT).…”

Section: Morphological Analysismentioning

confidence: 99%

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Differential and Converging Molecular Mechanisms of Antidepressants’ Action in the Hippocampal Dentate Gyrus

Patrício

Mateus‐Pinheiro

Irmler

et al. 2014

Neuropsychopharmacol

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Major depression is a highly prevalent, multidimensional disorder. Although several classes of antidepressants (ADs) are currently available, treatment efficacy is limited, and relapse rates are high; thus, there is a need to find better therapeutic strategies. Neuroplastic changes in brain regions such as the hippocampal dentate gyrus (DG) accompany depression and its amelioration with ADs. In this study, the unpredictable chronic mild stress (uCMS) rat model of depression was used to determine the molecular mediators of chronic stress and the targets of four ADs with different pharmacological profiles (fluoxetine, imipramine, tianeptine, and agomelatine) in the hippocampal DG. All ADs, except agomelatine, reversed the depression-like behavior and neuroplastic changes produced by uCMS. Chronic stress induced significant molecular changes that were generally reversed by fluoxetine, imipramine, and tianeptine. Fluoxetine primarily acted on neurons to reduce the expression of pro-inflammatory response genes and increased a set of genes involved in cell metabolism. Similarities were found between the molecular actions and targets of imipramine and tianeptine that activated pathways related to cellular protection. Agomelatine presented a unique profile, with pronounced effects on genes related to Rho-GTPase-related pathways in oligodendrocytes and neurons. These differential molecular signatures of ADs studied contribute to our understanding of the processes implicated in the onset and treatment of depression-like symptoms.

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Section: Neuroplastic Changes In the Hippocampal Dgsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 97%

Section: Morphological Analysismentioning

confidence: 99%

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Differential and Converging Molecular Mechanisms of Antidepressants’ Action in the Hippocampal Dentate Gyrus

Patrício

Mateus‐Pinheiro

Irmler

et al. 2014

Neuropsychopharmacol

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“…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). …”

mentioning

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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“…Des modifications de l'hippocampe sont également observées lors de stress intenses et prolongés Pinto et al, 2015;Polan & Hoffer, 2008). Au niveau cortical supérieur, soit les régions du cortex frontal, préfrontal et temporal, une activité métabolique limitée ainsi qu'un développement anormal de la substance blanche sont rapportés chez les enfants institutionnalisés ayant vécu de multiples formes de négligence Govindan, Behen, Helder, Makki, & Chugani, 2010).…”

Section: Les Mécanismes Du Stress Et La Réaction Face Aux Situations unclassified

L’impact des relations précoces sur le développement cérébral : le trouble réactionnel de l’attachement vu par les neurosciences

Neuville¹,

Puentes-Neuman²,

Terradas³

2017

La Psychiatrie De l'Enfant

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Table des Finalement, cela n'aurait pu être possible sans la précieuse collaboration des enfants participants et de leur famille, ni sans la contribution et la collaboration de l'équipe de pédopsychiatrie de l'Hôpital Charles LeMoyne, et tout particulièrement du Dr Claude Grenier, pédopsychiatre. Je vous remercie tous grandement. Merci également à Monsieur Jacques Bigras qui a su me redonner de la motivation au moment où le découragement pointait son nez. Avant-propos2 L'attachement est un champ de recherche fécond et stimulant depuis les premiers travaux de Bowlby au milieu du siècle dernier. Il sera d'ailleurs le premier à postuler que l'attachement sélectif précoce est la base indispensable pour le développement de relations sociales ultérieures fonctionnelles puisqu'il permet la régulation de la sécurité et de la survie de l'enfant (Bowlby, 1969(Bowlby, , 1973(Bowlby, , 1980Main, 1998 (Ainsworth et al., 1978; van IJzendoorn & Kroonenberg, 1988;van IJzendoorn, Schuengel, & Bakermans-Kranenburg, 1999). Le patron d'attachement désorganisé est d'ailleurs considéré comme un facteur de risque majeur associé au développement d'une psychopathologie chez l'enfant (Borelli, David, Crowley, & Mayes, 2010;Boris, Fueyo, & Zeanah, 1997, Green & Goldwyn, 2002Lyons-Ruth, 1996;Zeanah, Boris, & Larrieu, 1997;Zeanah, Boris, & Scheeringa, 1997). Une entité diagnostique semble conceptuellement liée à la désorganisation de l'attachement, il s'agit du trouble d'attachement. Cependant, bien que très perturbés, les enfants présentant un patron désorganisé ne développeront pas forcément un trouble d'attachement. La désorganisation de l'attachement est donc considérée comme distincte du trouble d'attachement mais constituant plutôt un facteur de risque (van IJzendoorn & Bakermans-Kranenburg, 2003).Le trouble d'attachement surviendrait lorsque l'enfant ne peut développer un lien significatif avec une personne disponible et sensible, de par l'absence ou le changement répété de figure de soins en bas âge. Bien que la maltraitance puisse survenir en même temps que des négligences graves ou des changements de soignant, elle serait insuffisante pour expliquer un trouble d'attachement (Boris, Zeanah, Larrieu, Scheeringa, & Heller, 1998;Smyke, Dumitrescu, & Zeanah, 2002). (Bowlby, 1973(Bowlby, , 1980. Une continuité et une corrélation sont effectivement observées entre les patrons d'attachement évalués durant la petite enfance et les représentations d'attachement inscrites dans les MOI étudiés à l'âge scolaire . Selon DeKlyen et , un attachement insécure aurait un impact important sur la future mésadaptation potentielle de l'individu de par la cristallisation des MOI, modèles caractérisés par de la colère, de la méfiance, de l'anxiété et de la peur. En effet, ces représentations d'attachement influencent l'ensemble des relations de la personne ainsi que ses capacités à négocier avec les diverses événements de sa vie . Kemeny, 2003;Thomas et al., 2001).De même, certaines études indiquent des perturbations au niveau des capacités d'apprent...

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Differential impact of chronic stress along the hippocampal dorsal–ventral axis

Cited by 62 publications

References 41 publications

Differential and Converging Molecular Mechanisms of Antidepressants’ Action in the Hippocampal Dentate Gyrus

Differential and Converging Molecular Mechanisms of Antidepressants’ Action in the Hippocampal Dentate Gyrus

Tau protein is essential for stress-induced brain pathology

L’impact des relations précoces sur le développement cérébral : le trouble réactionnel de l’attachement vu par les neurosciences

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