Repeated Unpredictable Stress and Antidepressants Differentially Regulate Expression of the Bcl-2 Family of Apoptotic Genes in Rat Cortical, Hippocampal, and Limbic Brain Structures

Kosten, Therese A.; Galloway, Matthew P.; Duman, Ronald S.; Russell, David; D’Sa, Carrol

doi:10.1038/sj.npp.1301527

Cited by 147 publications

(93 citation statements)

References 77 publications

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“…An intriguing one is the silencing of genes involved in structural and functional re-organization of learning and memory processes in the context of cell adhesion molecules, since maternal separation can cause irreversible changes in cognitive functions in the offspring. The finding that stress early in life causes delayed impairments of synaptic and cognitive measures of hippocampal function 35,36 requires investigation of permanent and irreversible changes in gene expression, often caused by silencing of genes via methylation of their promoter regions. In the present study we did not detect any increased DNA methylation in the hippocampus of adult mice of the promoters of all genes investigated.…”

Section: Discussionmentioning

confidence: 99%

Stress downregulates hippocampal expression of the adhesion molecules NCAM and CHL1 in mice by mechanisms independent of DNA methylation of their promoters

Desarnaud

Jakovcevski

Morellini

et al. 2008

Cell Adhesion & Migration

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Stress is an important physiological regulator of brain function in young and adult mammals. The mechanisms underlying regulation of the consequences of stress, and in particular severe chronic stress, are thus important to investigate. These consequences most likely involve changes in synaptic function of brain areas being part of neural networks that regulate responses to stress. Cell adhesion molecules have been shown to regulate synaptic function in the adult and we were thus interested to investigate a regulatory mechanism that could influence expression of three adhesion molecules of the immunoglobulin superfamily (NCAM, L1 and CHL1) after exposure of early postnatal and adult mice to repeated stress. We hypothesized that reduction of adhesion molecule expression after chronic stress, as observed previously in vivo, could be due to gene silencing of the three molecules by DNA methylation. Although adhesion molecule expression was reduced after exposure of C57BL/6 mice to stress, thus validating our stress paradigm as imposing changes in adhesion molecule expression, we did not observe differences in methylation of CpG islands in the promoter regions of NCAM, L1 and CHL1, nor in the promoter region of the glucocorticoid receptor in the hippocampus, the expression of which at the protein level was also reduced after stress. We must therefore infer that severe stress in mice of the C57BL/6 strain downregulates adhesion molecule levels by mechanisms that do not relate to DNA methylation.

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Section: Discussionmentioning

confidence: 99%

Stress downregulates hippocampal expression of the adhesion molecules NCAM and CHL1 in mice by mechanisms independent of DNA methylation of their promoters

Desarnaud

Jakovcevski

Morellini

et al. 2008

Cell Adhesion & Migration

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“…Magnetic resonance studies revealed that depression is accompanied by structural changes in the hippocampus, the prefrontal cortex, the amygdala, the anterior cingulate and the basal ganglia [26]. Enhanced apoptosis was detected in the brain structures of rats tested in animal models of depression, such as repeated unpredictable stress [10] and maternal separation [27]. We also demonstrated that [Bcl-2]/[Bax] ratio in the amygdaloid complex of fluoxetine treated traumatized rats was not different from the non-traumatized controls.…”

Section: Discussionmentioning

confidence: 99%

“…Fluoxetine, one of the selective serotonin reuptake inhibitors, shows a strong antidepressive effect and is widely used to augment the actions of serotonin in the nervous system [28][29][30]. The Bcl-2 and Bcl-xl proteins have a well-known antiapoptotic activity and it was formerly demonstrated that the antidepressants upregulated Bcl-2 mRNA in rat limbic structures and frontal cortex [10]. In that study it was demonstrated that fluoxetine did not affect Bcl-2 levels but decreased Bax expression in hippocampal subregions [10].…”

Section: Discussionmentioning

confidence: 99%

“…The Bcl-2 and Bcl-xl proteins have a well-known antiapoptotic activity and it was formerly demonstrated that the antidepressants upregulated Bcl-2 mRNA in rat limbic structures and frontal cortex [10]. In that study it was demonstrated that fluoxetine did not affect Bcl-2 levels but decreased Bax expression in hippocampal subregions [10]. The antiapoptotic effects of antidepressants were also confirmed by Xu et al [31], who found an enhanced intensity of Bcl-2 immunostaining in the hippocampal mossy fibers following chronic administration of amitriptyline and venlafaxine in low (5mg/ kg) but not in higher dosage (10 mg/kg) [31].…”

Section: Discussionmentioning

confidence: 99%

“…Apoptosis that occurs normally during development and aging and as a homeostatic mechanism to maintain cell populations in tissues that it can also be proposed to contribute to the structural alterations in the stress-related mood disorders [9][10][11]. The apoptotic process is programmed and critically controlled by the balance between proapoptotic and antiapoptotic proteins within the cell [12].…”

Section: Predator Scent Testmentioning

confidence: 99%

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Altered ratio of proapoptotic and antiapoptotic proteins in different brain regions of female rats in model of post-traumatic stress disorder

2015

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Objective: The B-cell lymphoma/leukemia-2 (Bcl-2) family of proteins governs mitochondrial membrane permeability where the programmed apoptotic process is controlled by the balance between proapoptotic (Bax) and antiapoptotic (Bcl-2) proteins. We aimed to investigate the [Bcl-2]/[Bax] in different brain regions in a post-traumatic stress disorder rat model. Methods: Female Sprague-Dawley rats were exposed to dirty cat litter (trauma) for 10 min and the protocol was repeated 1 week later with a trauma reminder (clean litter) in reversed 12 h light/dark cycle. The rats received intraperitoneal saline, fluoxetine (2.5 mg/kg/day) or propranolol (10 mg/kg/day) for 7 days between exposure sessions. Following exposure to the trauma reminder, elevated plus maze experiments were done. Immunoblotting was used to quantify and [Bax] proteins in the homogenates of the dorsal hippocampus, the frontal cortex and the amygdaloid complex. pathology of the disease [16] and our previous data indicated that the cat litter test is a reproducible experiment where the rats subjected to dirty cat litter (the trauma) had longer freezing times and higher anxiety indices when exposed to the situational reminder, the clean cat litter [17]. Our previous another data showed that noradrenaline (NA) content in the rostral pons increased in traumatized rats with cat litter and this increase may serve as an additional neurochemical evidence for the model. Pirenzepine suppressed the anxiety index but it was not that effective in decreasing the prolonged freezing times [18].In this current study, we wanted to demonstrate the ratio between proapoptotic and antiapoptotic proteins in the dorsal hippocampus, the amygdaloid complex and the frontal cortex of female rats traumatized with cat litter. The effects of fluoxetine or propranolol on behavioral parameters and neuronal apoptosis were also investigated.

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Timing‐specific associations between income‐to‐needs ratio and hippocampal and amygdala volumes in middle childhood: A preliminary study

Ramphal

Pagliaccio

Dworkin

et al. 2021

Developmental Psychobiology

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It is well known that financial disadvantage is associated with alterations in brain development in regions critical to socioemotional well-being such as the hippocampus and the amygdala. Yet little is known about whether family income at different points in development is differentially associated with these structures. Furthermore, little is known about which environmental factors statistically mediate associations between income and subcortical structure. Using a longitudinal birth cohort and linear mixedeffects models, we identified associations between income-to-needs ratio (INR) at 6 timepoints throughout childhood and hippocampal and amygdala volumes at age 7-9 years (n = 41; 236 INR measurements; 41 brain measurements). Mediation analysis identified environmental sequelae of income that statistically accounted for INR-brain associations. Lower INR prior to age 4 was associated with smaller hippocampal volumes, whereas lower INR prior to age 2 was associated with smaller right amygdala volume. These associations were mediated by unmet basic needs (e.g., food, housing).These findings delineate the temporal specificity of associations between income and hippocampal and amygdala structures.

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Repeated Unpredictable Stress and Antidepressants Differentially Regulate Expression of the Bcl-2 Family of Apoptotic Genes in Rat Cortical, Hippocampal, and Limbic Brain Structures

Cited by 147 publications

References 77 publications

Stress downregulates hippocampal expression of the adhesion molecules NCAM and CHL1 in mice by mechanisms independent of DNA methylation of their promoters

Stress downregulates hippocampal expression of the adhesion molecules NCAM and CHL1 in mice by mechanisms independent of DNA methylation of their promoters

Altered ratio of proapoptotic and antiapoptotic proteins in different brain regions of female rats in model of post-traumatic stress disorder

Timing‐specific associations between income‐to‐needs ratio and hippocampal and amygdala volumes in middle childhood: A preliminary study

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