Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement

Sousa, Nuno; Lukoyanov, Nikolay; Madeira, M. Dulce; Almeida, Osborne F. X.; Paula‐Barbosa, M. M.

doi:10.1016/s0306-4522(00)00050-6

Cited by 684 publications

(569 citation statements)

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“…As noted above, a ment [19,141]. Moreover, we also noted that both Dilantin recent study showed that a chronic multiple stress and tianeptine prevent dendritic remodelling caused by paradigm, which is designed to avoid habituation of repeated restraint stress and glucocorticoid injections.…”

Section: Stress Adaptive Plasticity and The Hippocampusmentioning

confidence: 61%

“…weeks has demonstrated that the remodelling of dendrites There is evidence for interactions between serotonin and found in CA3 also occurs in the dentate gyrus and in CA 1, NMDA receptors, indicating that serotonin potentiates although the effects in the CA3 tend to be the greatest NMDA receptor binding as well as activity of NMDA [141] (see Fig. 5).…”

Section: Stress Adaptive Plasticity and The Hippocampusmentioning

confidence: 97%

“…Moreover, we also noted that both Dilantin recent study showed that a chronic multiple stress and tianeptine prevent dendritic remodelling caused by paradigm, which is designed to avoid habituation of repeated restraint stress and glucocorticoid injections. glucocorticoid responses to the same stressor, produced Treatment with tianeptine is able to reverse the remodeldendritic remodelling not only in the CA3 region of the ling produced by 21 days oral corticosterone and to do so hippocampus but also in the dentate gyrus and CA1 [141].…”

Section: Stress Adaptive Plasticity and The Hippocampusmentioning

confidence: 99%

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The neurobiology of stress: from serendipity to clinical relevance11Published on the World Wide Web on 22 November 2000.

2000

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The hormones and other physiological agents that mediate the effects of stress on the body have protective and adaptive effects in the short run and yet can accelerate pathophysiology when they are over-produced or mismanaged. Here we consider the protective and damaging effects of these mediators as they relate to the immune system and brain. 'Stress' is a principle focus, but this term is rather imprecise. Therefore, the article begins by noting two new terms, allostasis and allostatic load that are intended to supplement and clarify the meanings of 'stress' and 'homeostasis'. For the immune system, acute stress enhances immune function whereas chronic stress suppresses it. These effects can be beneficial for some types of immune responses and deleterious for others. A key mechanism involves the stress-hormone dependent translocation of immune cells in the blood to tissues and organs where an immune defense is needed. For the brain, acute stress enhances the memory of events that are potentially threatening to the organism. Chronic stress, on the other hand, causes adaptive plasticity in the brain, in which local neurotransmitters as well as systemic hormones interact to produce structural as well as functional changes, involving the suppression of ongoing neurogenesis in the dentate gyrus and remodelling of dendrites in the Ammon's horn. Under extreme conditions only does permanent damage ensue. Adrenal steroids tell only part of the story as far as how the brain adapts, or shows damage, and local tissue modulators -cytokines for the immune response and excitatory amino acid neurotransmitters for the hippocampus. Moreover, comparison of the effects of experimenter-applied stressors and psychosocial stressors show that what animals do to each other is often more potent than what experimenters do to them. And yet, even then, the brain is resilient and capable of adaptive plasticity. Stress-induced structural changes in brain regions such as the hippocampus have clinical ramifications for disorders such as depression, post-traumatic stress disorder and individual differences in the aging process.

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Section: Stress Adaptive Plasticity and The Hippocampusmentioning

confidence: 61%

Section: Stress Adaptive Plasticity and The Hippocampusmentioning

confidence: 97%

Section: Stress Adaptive Plasticity and The Hippocampusmentioning

confidence: 99%

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The neurobiology of stress: from serendipity to clinical relevance11Published on the World Wide Web on 22 November 2000.

2000

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“…1,17 If GR-induced hippocampal cell losses do indeed contribute to impaired regulation of the HPA axis, eventually leading to mood, anxiety and cognitive impairments, therapeutic tools designed to selectively activate MR or to specifically improve their signaling efficiency in neurons 49,50 would be a worthwhile strategy. In closing, it however needs to be emphasized that, even if deserving of further investigation with respect to functional significance, the contribution of apoptotic events to hypercortisolemia-induced reductions in hippocampal size are unlikely to be major; as discussed elsewhere, 12 the fact that recovery of both the morphological and behavioral changes caused by elevated corticosteroid secretion are possible after normocortisolemia has been reestablished, 8,51 suggesting that the reported reductions in hippocampal volume are partially due to neuritic atrophy rather than irreversible cell death.…”

Section: Discussionmentioning

confidence: 99%

Direct targeting of hippocampal neurons for apoptosis by glucocorticoids is reversible by mineralocorticoid receptor activation

et al. 2005

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An important question arising from previous observations in vivo is whether glucocorticoids can directly influence neuronal survival in the hippocampus. To this end, a primary postnatal hippocampal culture system containing mature neurons and expressing both glucocorticoid (GR) and mineralocorticoid (MR) receptors was developed. Results show that the GR agonist dexamethasone (DEX) targets neurons (microtubule-associated protein 2-positive cells) for death through apoptosis. GR-mediated cell death was counteracted by the MR agonist aldosterone (ALDO). Antagonism of MR with spironolactone ([7a-(acetylthio)-3-oxo-17a-pregn-4-ene-21 carbolactone] (SPIRO)) causes a dose-dependent increase in neuronal apoptosis in the absence of DEX, indicating that nanomolar levels of corticosterone present in the culture medium, which are sufficient to activate MR, can mask the apoptotic response to DEX. Indeed, both SPIRO and another MR antagonist, oxprenoate potassium ((7a,17a)-17-hydroxy-3-oxo-7-propylpregn-4-ene-21-carboxylic acid, potassium salt (RU28318)), accentuated DEX-induced apoptosis. These results demonstrate that GRs can act directly to induce hippocampal neuronal death and that demonstration of their full apoptotic potency depends on abolition of survival-promoting actions mediated by MR. Molecular Psychiatry (2005) 10, 790-798.

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“…It is also established that glucocorticoid excess decreases neurogenesis in the adult dentate gyrus (Gould and Tanapat, 1999). These structural effects are mirrored in an attenuation of long-term potentiation (LTP) (Pavlides et al, 1993;Smriga et al, 1996) and an impairment of hippocampally mediated spatial memory performance in rodents (Sousa et al, 2000). However, glucocorticoids show a Ushaped dose-response curve with respect to the structure and function of hippocampal neurons, and reduction or removal of circulating glucocorticoids by adrenalectomy (ADX) also has deleterious effects on hippocampus.…”

Section: Introductionmentioning

confidence: 99%

Flattening the Glucocorticoid Rhythm causes Changes in Hippocampal Expression of Messenger RNAs Coding Structural and Functional Proteins: Implications for Aging and Depression

Gartside

Leitch

McQuade

et al. 2002

Neuropsychopharmacol

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Subtle changes in glucocorticoid levels, including a flattening of the diurnal rhythm with raised nadir, are prevalent, being characteristic of both aging and major depression. Both these conditions are also associated with deficits in hippocampally mediated cognitive functions. We hypothesized that this profile of glucocorticoid levels causes structural and functional changes in the hippocampus, which in turn may engender cognitive deficits. We implanted slow-release corticosterone pellets into adrenally intact adult male rats to produce a flattened glucocorticoid rhythm with levels clamped midway between the normal nadir and zenith. Using density profile analysis we measured hippocampal expression of messenger RNAs encoding structural and functional proteins. In rats with a flattened glucocorticoid rhythm, the expression of the mRNA coding for microtubule associated protein-2b (MAP2b) was reduced in CA3 relative to sham-operated controls, but unchanged in dentate gyrus and CA1. In contrast, the expression of the mRNA coding the alpha subunit of calciumcalmodulin dependent kinase (CAMKIIa) was reduced in dentate gyrus in animals with a flattened glucocorticoid rhythm, but unchanged in CA3. The expression of the mRNA coding the synaptic vesicle protein synaptophysin was unchanged in both CA3 and dentate gyrus. The data indicate that a flattening of the normal diurnal glucocorticoid rhythm decreases the hippocampal expression of mRNAs coding key structural and functional proteins, and does so in a regionally selective manner. The data may have relevance for cognitive deficits characteristic of aging and depression.

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Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement

Cited by 684 publications

References 68 publications

The neurobiology of stress: from serendipity to clinical relevance11Published on the World Wide Web on 22 November 2000.

The neurobiology of stress: from serendipity to clinical relevance11Published on the World Wide Web on 22 November 2000.

Direct targeting of hippocampal neurons for apoptosis by glucocorticoids is reversible by mineralocorticoid receptor activation

Flattening the Glucocorticoid Rhythm causes Changes in Hippocampal Expression of Messenger RNAs Coding Structural and Functional Proteins: Implications for Aging and Depression

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