Chronic Stress Triggers Expression of Immediate Early Genes and Differentially Affects the Expression of AMPA and NMDA Subunits in Dorsal and Ventral Hippocampus of Rats

Pacheco, Aníbal; Aguayo, Felipe I.; Aliaga, Esteban; Muñoz, Mauricio; García-Rojo, Gonzalo; Olave, Felipe Antonio; Parra-Fiedler, Nicolas A.; García-Pérez, Alexandra; Tejos-Bravo, Macarena; Rojas, Paulina S.; Parra, C.; Fiedler, Jenny L.

doi:10.3389/fnmol.2017.00244

Cited by 45 publications

(40 citation statements)

References 77 publications

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“…It is worth noting that brain tissues were extracted from the entire hippocampus in this study. Considering that glutamate receptor subunits are differentially expressed and regulated in dorsal and ventral hippocampus (Pandis et al, 2006 ; Pacheco et al, 2017 ), future studies are needed to scrutinize MK-801-induced effects on glutamate receptor subunits in each subregion and to examine how these effects can be modulated by antipsychotic treatment.…”

Section: Discussionmentioning

confidence: 99%

Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits

Liu

Guo

et al. 2018

Front. Behav. Neurosci.

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Cognitive dysfunction constitutes an essential component in schizophrenia for its early presence in the pathophysiology of the disease and close relatedness to life quality of patients. To develop effective treatment of cognitive deficits, it is important to understand their neurobiological causes and to identify potential therapeutic targets. In this study, adopting repeated MK-801 treatment as an animal model of schizophrenia, we investigated whether antipsychotic drugs, olanzapine and haloperidol, can reverse MK-801-induced cognitive deficits and how the reversal processes recruited proteins involved in glutamate neurotransmission in rat medial prefrontal cortex (mPFC) and hippocampus. We found that low-dose chronic MK-801 treatment impaired object-in-context recognition memory and reversal learning in the Morris water maze, leaving reference memory relatively unaffected, and that these cognitive deficits can be partially reversed by olanzapine, not haloperidol, treatment. At the molecular level, chronic MK-801 treatment resulted in the reduction of multiple N-methyl-D-aspartate (NMDA) receptor subunits in rat mPFC and olanzapine, not haloperidol, treatment restored the levels of GluN1 and phosphorylated GluN2B in this region. Taken together, MK-801-induced cognitive deficits may be associated with region-specific changes in NMDA receptor subunits and the reversal of specific NMDA receptor subunits may underlie the cognition-enhancing effects of olanzapine.

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Section: Discussionmentioning

confidence: 99%

Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits

Liu

Guo

et al. 2018

Front. Behav. Neurosci.

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“…NMDA receptor subunits (NR1, NR2A, and NR2B) and AMPA receptor subunits (GluA1 and GluA2) are closely involved in brain function, and are also important targets of chronic stress ( Costa-Nunes et al, 2014 ; Pacheco et al, 2017 ; Shang et al, 2017 ; Arcego et al, 2018 ). The effects of chronic stress on NMDA and AMPA receptors vary based on the type of stress.…”

Section: Discussionmentioning

confidence: 99%

“…The effects of chronic stress on NMDA and AMPA receptors vary based on the type of stress. For example, Pacheco et al (2017) found that restraint stress (2.5 h/day) for 14 days triggered an increase in NR1 protein level in the dorsal hippocampus. Arcego et al (2018) found that social isolation stress increased the expression of subunit NR2A of the NMDA receptor.…”

Section: Discussionmentioning

confidence: 99%

Inhibiting RIP1 Improves Chronic Stress-Induced Cognitive Impairments in D-Galactose-Induced Aging Mice

Wang

et al. 2018

Front. Behav. Neurosci.

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Mounting evidence shows that chronic stress can affect both the structure and function of the brain resulting in decreased synaptic plasticity and cognitive dysfunction. Although several studies have indicated that aged brains are more vulnerable to chronic stress, it remains unknown how to prevent stress-induced memory deficits in aged animals. Neuroinflammation plays an important role in the pathogenesis of chronic stress-related brain dysfunction. Receptor-interacting protein 1 (RIP1) is a key molecule that can modulate inflammation, apoptosis, and necroptosis. Here, we investigated whether inhibiting RIP1 using necrostatin-1 during chronic stress could improve chronic stress-related brain dysfunction in D-galactose-induced aging mice. The stressed mice underwent restraint stress for 14 days. Necrostatin-1 (6.25 mg/kg) or vehicle was administered intraperitoneally once every 3 days during the stress period. Locomotor activity was tested using the open field test and cognitive function was assessed using the novel object recognition and Barnes maze tests. The hippocampus was collected to assess neuroinflammation (Iba1, IL-1α, IL-1β, TNF-α, and C1q), necroptosis [RIP1, RIP3, mixed lineage kinase domain-like (MLKL), and NF-κB], neuroplasticity (doublecortin, NR1, NR2A, NR2B, GluA1, and GluA2), and the expression of glucocorticoid and mineralocorticoid receptors. Blood samples were collected to quantify the levels of corticosterone. We found that chronic stress induced obvious memory impairment and neuroinflammation, decreased neurogenesis and GluA2 expression, and increased the expression of RIP1 and NF-κB. Inhibiting RIP1 by necrostatin-1 during chronic stress rescued the memory impairment and alleviated the pathological changes induced by stress. These suggest that inhibiting RIP1 using necrostatin-1 improves chronic stress-related brain dysfunction in D-galactose-induced aging mice. The potential mechanisms include limitation of neuroinflammation and the rescue of neurogenesis and GluA2 expression.

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“…PPT in the hippocampus of female rats and mice (Li et al, 2004;Waters et al, 2009) and because it's reduced in the PFC of individuals with MDD (Feyissa et al, 2009) and with chronic stress exposure in rodents (Kallarackal et al, 2013;Kim and Leem, 2016;Pacheco et al, 2017). PSD-95 protein expression was quantified in hippocampus and frontal cortex samples using a PSD-95 kit from MSD (catalogue no.…”

Section: Psd-95 Quantification: Psd-95 Was Quantified Because Its Expmentioning

confidence: 99%

“…Estradiol and ERα or β agonist upregulate the expression of synaptic proteins in female rats (Waters et al, 2009), including the postsynaptic density protein 95 (PSD-95), a scaffolding protein which organizes synaptic elements that are important for synaptic function and plasticity (Kim and Sheng, 2004). Importantly, PSD-95 is reduced in the prefrontal cortex (PFC) of individuals with MDD (Feyissa et al, 2009) and in animal models of stress exposure (Kallarackal et al, 2013;Kim and Leem, 2016;Pacheco et al, 2017). Yet, whether and by what receptor mechanisms can 17β-estradiol influence the effects of stress on PSD-95 remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Selective activation of estrogen receptors α and β: Implications for depressive-like phenotypes in female mice exposed to chronic unpredictable stress

Eid

Lieblich

Duarte‐Guterman

et al. 2019

Preprint

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The estrogen receptor (ER) mechanisms by which 17β-estradiol influences depressive-like behaviour have primarily been investigated acutely and not within an animal model of depression. Therefore, the current study aimed to dissect the contribution of ERα and ERβ to the effects of 17β-estradiol under non-stress and chronic stress conditions. Ovariectomized (OVX) or sham-operated mice were treated chronically (47 days) with 17β-estradiol (E2), the ERβ agonist diarylpropionitrile (DPN), the ERα agonist propylpyrazole-triol (PPT), or vehicle. On day 15 of treatment, mice from each group were assigned to Chronic Unpredictable Stress (CUS; 28 days) or non-CUS conditions. Mice were assessed for anxiety-and depressive-like behaviour and hypothalamic-pituitary-adrenal (HPA) axis function.Immune mediators and markers of plasticity (postsynaptic density protein 95 and neurogenesis) were measured in the hippocampus and frontal cortex. Overall, the effects of CUS were more robust that those of estrogenic treatments, as seen by increased immobility in the tail suspension test (TST), reduced PSD-95 expression, reduced neurogenesis in the ventral hippocampus, and HPA axis negative feedback dysregulation. However, we also observe CUS-dependent and -independent effects of ovarian status and estrogenic treatments. The effects of CUS on PSD-95 expression, the cytokine milieu, and in TST were largely driven by PPT and DPN, indicating that these treatments were not protective.Independent of CUS, estradiol increased neurogenesis in the ventral hippocampus, blunted the corticosterone response to an acute stressor, but increased anxiety-like behaviour. These findings provide insights into the complexities of estrogen signaling in modulating depressive-like phenotypes under non-stress and chronic stress conditions.

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Chronic Stress Triggers Expression of Immediate Early Genes and Differentially Affects the Expression of AMPA and NMDA Subunits in Dorsal and Ventral Hippocampus of Rats

Cited by 45 publications

References 77 publications

Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits

Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits

Inhibiting RIP1 Improves Chronic Stress-Induced Cognitive Impairments in D-Galactose-Induced Aging Mice

Selective activation of estrogen receptors α and β: Implications for depressive-like phenotypes in female mice exposed to chronic unpredictable stress

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