Chronic restraint stress induces an isoform-specific regulation on the neural cell adhesion molecule in the hippocampus

Maria del Carmen Sandi Perez
2002
Article

Résumé

Existing evidence indicates that 21-days exposure of rats to restraint stress induces dendritic atrophy in pyramidal cells of the hippocampus. This phenomenon has been related to altered performance in hippocampal-dependent learning tasks. Prior studies have shown that hippocampal expression of cell adhesion molecules is modified by such stress treatment, with the neural cell adhesion molecule (NCAM) decreasing and L1 increasing, their expression, at both the mRNA and protein levels. Given that NCAM comprises several isoforms, we investigated here whether chronic stress might differentially affect the expression of the three major isoforms (NCAM-120, NCAM-140, NCAM-180) in the hippocampus. In addition, as glucocorticoids have been implicated in the deleterious effects induced by chronic stress, we also evaluated plasma corticosterone levels and the hippocampal expression of the corticosteroid mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). The results showed that the protein concentration of the NCAM-140 isoform decreased in the hippocampus of stressed rats. This effect was isoform-specific, because NCAM-120 and NCAM-180 levels were not significantly modified. In addition, whereas basal levels of plasma corticosterone tended to be increased, MR and GR concentrations were not significantly altered. Although possible changes in NCAM-120, NCAM-180 and corticosteroid receptors at earlier time points of the stress period cannot be ignored, this study suggests that a down-regulation of NCAM-140 might be implicated in the structural alterations consistently shown to be induced in the hippocampus by chronic stress exposure. As NCAM-140 is involved in cell-cell adhesion and neurite outgrowth, these findings suggest that this molecule might be one of the molecular mechanisms involved in the complex interactions among neurodegeneration-related events

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Maria del Carmen Sandi Perez
2002
Article

Résumé

Official source

https://infoscience.epfl.ch/record/125750?ln=fr

À propos de ce résultat

Concepts associés (13)

Concepts associés

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Publications associées (16)

Publications associées

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Prior exposure to a single stress session facilitates subsequent contextual fear conditioning in rats. Evidence for a role of corticosterone

Maria Isabel Cordero Campana, Maria del Carmen Sandi Perez

Previous studies showed that exposure of rats to chronic restraint stress for 21 days enhances subsequent contextual fear conditioning. Since recent evidence suggest that this effect is not dependent on stress-induced neurodegenerative processes, but to elevated training-elicited glucocorticoid release in chronically stressed animals, we aimed to explore here whether a single exposure to restraint stress, which is not expected to induce neuronal damage, would also affect contextual fear conditioning. We also questioned whether post-training corticosterone levels might be associated with any potential effect of stress on fear conditioning. Adult male Wistar rats were exposed to acute restraint stress for 2 h and, two days later, trained in the contextual fear conditioning task, under training conditions involving either moderate (0.4 mA shock) or high (1 mA shock) stress levels. The results showed that acute stress enhanced conditioned freezing at both training conditions, although data from the 1 mA shock intensity experiment only approached significance. Stressed animals were shown to display higher post-training corticosterone levels. Furthermore, the facilitating effect of prior stress was not evident when animals were trained in the hippocampal-independent auditory-cued conditioning task. Therefore, these findings support the idea that stress experiences preceding exposure to new types of stressors facilitate the development of contextual fear conditioning. They also indicate that not only repeated, but also a single exposure to aversive stimulation is sufficient to facilitate context-dependent fear conditioning, and suggest that increased glucocorticoid release at training might be implicated in the mechanisms mediating the memory facilitating effects induced by prior stress experiences.

2003

Chargement

Humans show inter-individual differences in vulnerability to develop post-traumatic stress disorder (PTSD) following exposure to trauma. Several critical biobehavioral features have been consistently described in PTSD patients, including blunted cortisol levels, smaller hippocampal size, sleep disturbances. However, because of the delay between trauma exposure and the onset of symptoms characteristic of PTSD, only a few longitudinal studies have tried to dissect whether these features constitute pre-trauma risk factors or consequences of the trauma. Enormous effort in animal and human studies has been dedicated to understanding mechanisms of conditioned fear and fear extinction, processes that are at the core of PTSD. However, the same progress has not been translated into psychiatric practice for PTSD. Deepening our understanding of the contribution of key factors to PTSD-related alterations can serve to develop effective treatments.In particular, with regard to low cortisol levels in PTSD pathophysiology, a causative role for blunted glucocorticoid responsiveness in PTSD has not been demonstrated yet.Here, we have addressed this question in lines of Wistar rats genetically-selected for their differential habituation of glucocorticoid responses to stress (LOW-, INTER-, HIGH-CORT Responder rats) and focused on fear extinction, a hallmark of PTSD symptomology, as one of the key features. As a first step, we looked whether divergent trajectories of glucocorticoid responsiveness were associated with brain volume abnormalities, prompted by the influential role of glucocorticoid in brain development. Notably, rats with low or high corticosterone responsiveness exhibit smaller hippocampi, regardless of trauma exposure, compared to rats with normative corticosterone levels. Similarly, the distribution of corticosteroid receptors in the hippocampus presented similarities between the LOW-CR and the HIGH-CR rats with higher mineralocorticoid receptors (MR) and less glucocorticoid receptors (GR). Although LOW- and HIGH-CR rats displayed a similar hippocampal profile at the structural and molecular levels, only LOW-CR male rats exhibited strong deficits in extinction consolidation compared to rats with 'normative' glucocorticoid responses (INTER-CR rats), and showed higher fear response both at few days and at several weeks after trauma exposure. We next tested the causal involvement of corticosterone in the fear extinction consolidation, and found that post-extinction corticosterone treatment markedly prevented the deficits in extinction memory and attenuated fear relapse. In addition, pharmacological inhibition of corticosterone levels during extinction memory consolidation, but not during training, in the INTER-CR rats led to extinction deficits at retrieval one day later. These results indicate that blunted corticosterone levels contribute to confer major vulnerability than having a small hippocampus, and that consolidation processes following extinction are mainly affected by low corticosterone levels.It is well known that glucocorticoids play an important role in memory consolidation processes and that sleep disturbances are a diagnostic criterion of PTSD. Therefore, we investigated in greater detail the sleep architecture in undisturbed condition and during the consolidation period of the extinction phase, which is known to be supported by sleep-dependent processes. In polysomnographic recordings, we found that rats with blunted corticos

EPFL2022

Chargement

Chronic stress induces opposite changes in the mRNA expression of the cell adhesion molecules NCAM and L1

Maria del Carmen Sandi Perez

The effects of 21-day exposure to restraint stress on mRNA levels of the cell adhesion molecules NCAM and L1 were evaluated in different hippocampal regions (CA1, CA3, and dentate gyrus) and other structures (thalamus, prefrontal and frontal cortices, and striatum) of the rat brain. A general decrease in gene expression of the neural cell adhesion molecule (NCAM) was found throughout the brain, particularly in all hippocampal subregions. On the contrary, transcripts for the adhesion molecule L1 were specifically increased at the level of the hippocampus, especially in the dorsal dentate gyrus and area CA3. mRNA for the NCAM180 isoform was detected unchanged in all brain areas examined after chronic stress. A second experiment explored whether there would be cognitive alterations associated with this stress procedure and molecular regulation. Thus, after exposure to the same restraint regimen, performance in the water maze was evaluated. Although stressed rats displayed the ability to learn the task throughout the training session, they showed a transient deficit in the initial phase of the acquisition. In conclusion, our findings indicate that chronic stress interferes with the mechanisms involved in the synthesis of cell adhesion molecules of the immunoglobulin superfamily. Furthermore, they suggest that these effects might be involved in the mechanisms by which stress induces structural and functional alterations in the central nervous system and, particularly, in the hippocampus.

2002

Chargement

EPFL2022

Prior exposure to a single stress session facilitates subsequent contextual fear conditioning in rats. Evidence for a role of corticosterone

Maria Isabel Cordero Campana, Maria del Carmen Sandi Perez

2003