Lasting downregulation of the lipid peroxidation enzymes in the prefrontal cortex of mice susceptible to stress-induced anhedonia

Cline, Brandon H.; Anthony, Daniel C.; Lysko, Alexander; Dolgov, Oleg; Anokhin, Konstantin V.; Schroeter, Careen A.; Malin, Dmitry; Kubatiev, A. A.; Steinbusch, Harry W.M.; Lesch, Klaus‐Peter; Strekalova, Tatyana

doi:10.1016/j.bbr.2014.04.037

Cited by 31 publications

(45 citation statements)

References 61 publications

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“…While recent studies suggest that challenging insulin receptor mediated transmission in the brain might have long-term effects lasting for weeks (Hoyer, 2003), we trust that the ameliorative action of DS reported here on sleep rebound is likely to be related to a reduced manifestations of depressive-like changes and stress response in chronically stressed mice that was found to be elevated for weeks in the model applied here when no antidepressant therapies are used (Cline et al, 2015). At the same time, power spectra activity was not changed in DS-treated mice (Figure 2C, Supplementary Table 2) ruling out non-specific general changes in EEG activity of the treatment and suggesting preserved cerebral homeostasis in DS-treated mice that can be compromised by some antidepressants or aging (Cespuglio et al, 1999; Clement et al, 2003).…”

Section: Discussionsupporting

confidence: 61%

“…Stressed mice treated with DS showed no significant change in sucrose preference measured after the 10th day of stress as compared to control animals (Figure 2A), similarly to the effects of classical antidepressants (Costa-Nunes et al, 2014; Cline et al, 2015; Strekalova et al, 2015). Earlier, we have shown in a model of stress-induced anhedonia that the decrease in sucrose preference is paralleled by a reduction in sucrose intake (Strekalova et al, 2004, 2006).…”

Section: Discussionsupporting

confidence: 54%

“…The apparatus was placed on a dark surface in order to reduce reflection and maintain control over lighting conditions during testing. Anxiety-like behavior was assessed using previously validated parameters that were scored manually as described elsewhere (Strekalova and Steinbusch, 2010; Costa-Nunes et al, 2014; Cline et al, 2015). Mice were placed in one of the closed-arm compartments of the apparatus.…”

Section: Methodsmentioning

confidence: 99%

“…The current reference antidepressant treatment was selected because of its effects in lowering the rate of stress-induced anhedonia over other methods of delivery and doses of antidepressants (Costa-Nunes et al, 2012, 2014; Strekalova et al, 2013; Cline et al, 2015). Previous experiments revealed an antidepressant-like effect of 1-week pre-treatment with daily i.p.…”

Section: Methodsmentioning

confidence: 99%

“…In the first experiment, using a model of stress-induced anhedonia (Strekalova and Steinbusch, 2010; Costa-Nunes et al, 2014; Cline et al, 2015) we investigated whether a pre-treatment in C57BL6J mice with DS, at the dose of 25 mg/kg/day intraperitoneally for 7 days, would improve normal sleep rebound (augmentation) following acute stress, a sign of adaptive stress response (Marinesco et al, 1999; Suchecki et al, 2012; Albu et al, 2014; Keshavarzy et al, 2014), as well as contextual fear conditioning learning that is regarded to be related to the adaptive sleep function (Rolls et al, 2013; Barnes and Wilson, 2014). Also, we studied hippocampal gene expression of NMDA receptor subunit NR2A and the ratio of NR2A/NR2B, whose increases were previously demonstrated to accompany a development of stress-induced anhedonia in the here applied chronic stress model (Costa-Nunes et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression

Cline

Costa-Nunes

Cespuglio

et al. 2015

Front. Behav. Neurosci.

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Central insulin receptor-mediated signaling is attracting the growing attention of researchers because of rapidly accumulating evidence implicating it in the mechanisms of plasticity, stress response, and neuropsychiatric disorders including depression. Dicholine succinate (DS), a mitochondrial complex II substrate, was shown to enhance insulin-receptor mediated signaling in neurons and is regarded as a sensitizer of the neuronal insulin receptor. Compounds enhancing neuronal insulin receptor-mediated transmission exert an antidepressant-like effect in several pre-clinical paradigms of depression; similarly, such properties for DS were found with a stress-induced anhedonia model. Here, we additionally studied the effects of DS on several variables which were ameliorated by other insulin receptor sensitizers in mice. Pre-treatment with DS of chronically stressed C57BL6 mice rescued normal contextual fear conditioning, hippocampal gene expression of NMDA receptor subunit NR2A, the NR2A/NR2B ratio and increased REM sleep rebound after acute predation. In 18-month-old C57BL6 mice, a model of elderly depression, DS restored normal sucrose preference and activated the expression of neural plasticity factors in the hippocampus as shown by Illumina microarray. Finally, young naïve DS-treated C57BL6 mice had reduced depressive- and anxiety-like behaviors and, similarly to imipramine-treated mice, preserved hippocampal levels of the phosphorylated (inactive) form of GSK3 beta that was lowered by forced swimming in pharmacologically naïve animals. Thus, DS can ameliorate behavioral and molecular outcomes under a variety of stress- and depression-related conditions. This further highlights neuronal insulin signaling as a new factor of pathogenesis and a potential pharmacotherapy of affective pathologies.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionsupporting

confidence: 54%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression

Cline

Costa-Nunes

Cespuglio

et al. 2015

Front. Behav. Neurosci.

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Molecular signature of excessive female aggression: study of stressed mice with genetic inactivation of neuronal serotonin synthesis

Strekalova,

Moskvin,

Jain

et al. 2023

J Neural Transm

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Aggression is a complex social behavior, critically involving brain serotonin (5-HT) function. The neurobiology of female aggression remains elusive, while the incidence of its manifestations has been increasing. Yet, animal models of female aggression are scarce. We previously proposed a paradigm of female aggression in the context of gene x environment interaction where mice with partial genetic inactivation of tryptophan hydroxylase-2 (Tph2+/− mice), a key enzyme of neuronal 5-HT synthesis, are subjected to predation stress resulting in pathological aggression. Using deep sequencing and the EBSeq method, we studied the transcriptomic signature of excessive aggression in the prefrontal cortex of female Tph2+/− mice subjected to rat exposure stress and food deprivation. Challenged mutants, but not other groups, displayed marked aggressive behaviors. We found 26 genes with altered expression in the opposite direction between stressed groups of both Tph2 genotypes. We identified several molecular markers, including Dgkh, Arfgef3, Kcnh7, Grin2a, Tenm1 and Epha6, implicated in neurodevelopmental deficits and psychiatric conditions featuring impaired cognition and emotional dysregulation. Moreover, while 17 regulons, including several relevant to neural plasticity and function, were significantly altered in stressed mutants, no alteration in regulons was detected in stressed wildtype mice. An interplay of the uncovered pathways likely mediates partial Tph2 inactivation in interaction with severe stress experience, thus resulting in excessive female aggression.

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Sodium Phenylbutyrate and Edaravone Abrogate Chronic Restraint Stress-Induced Behavioral Deficits: Implication of Oxido-Nitrosative, Endoplasmic Reticulum Stress Cascade, and Neuroinflammation

et al. 2016

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Chronic stress exposure can produce deleterious effects on the hippocampus (HC) which eventually leads to cognitive impairment and depression. Endoplasmic reticulum (ER) stress has been reported as one of the major culprits in the development of stress-induced cognitive impairment and depression. We investigated the neuroprotective efficacy of sodium phenylbutyrate (SPB), an ER stress inhibitor, and edaravone, a free radical scavenger, against chronic restraint stress (CRS)-induced cognitive deficits and anxiety- and depressive-like behavior in mice. Adult male Swiss albino mice were restrained for 6 h/day for 28 days and injected (i.p.) with SPB (40 and 120 mg/kg) or edaravone (3 and 10 mg/kg) for the last seven days. After stress cessation, the anxiety- and depressive-like behavior along with spatial learning and memory were examined. Furthermore, oxido-nitrosative stress, proinflammatory cytokines, and gene expression level of ER stress-related genes were assessed in HC and prefrontal cortex (PFC). CRS-exposed mice showed anxiety- and depressive-like behavior, which was significantly improved by SPB and edaravone treatment. In addition, SPB and edaravone treatment significantly alleviated CRS-induced spatial learning and memory impairment. Furthermore, CRS-evoked oxido-nitrosative stress, neuroinflammation, and depletion of Brain-derived neurotrophic factor were significantly ameliorated by SPB and edaravone treatment. We found significant up-regulation of ER stress-related genes in both HC and PFC regions, which were suppressed by SPB and edaravone treatment in CRS mice. Our study provides evidence that SPB and edaravone exerted neuroprotective effects on CRS-induced cognitive deficits and anxiety- and depressive-like behavior, which is possibly coupled with inhibition of oxido-nitrosative stress, neuroinflammation, and ER stress cascade.

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Lasting downregulation of the lipid peroxidation enzymes in the prefrontal cortex of mice susceptible to stress-induced anhedonia

Cited by 31 publications

References 61 publications

Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression

Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression

Molecular signature of excessive female aggression: study of stressed mice with genetic inactivation of neuronal serotonin synthesis

Sodium Phenylbutyrate and Edaravone Abrogate Chronic Restraint Stress-Induced Behavioral Deficits: Implication of Oxido-Nitrosative, Endoplasmic Reticulum Stress Cascade, and Neuroinflammation

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