Long‐Term Effects of Maternal Deprivation on Redox Regulation in Rat Brain: Involvement of NADPH Oxidase

Markovic, Branka; Radonjić, Nevena V.; Jevtic, G.; Stojković, T.; Velimirović, M.; Aksić, Milan; Poleksic, Joko; Nikolić, Tatjana; Aleksić, Dubravka; Radonjić, Vidosava; Filipović, Branislav; Petronijević, Nataša

doi:10.1155/2017/7390516

Cited by 14 publications

(8 citation statements)

References 65 publications

(62 reference statements)

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“…This is particularly pertinent to parvalbumin-expressing neurons, which are known to downregulate parvalbumin expression upon oxidative stress and in schizophrenia patients (Akbarian et al, 1995 ; Schmalbach et al, 2015 ; Janickova and Schwaller, 2020 ). Our previous work has shown that MD rats have indeed increased levels of oxidative stress, as well as higher numbers of microglial cells in the hippocampus (Marković et al, 2017 ). Another possible interpretation of our results would be that degeneration and loss of interneurons occur at the later stage, between 15 and 60 days of age.…”

Section: Discussionmentioning

confidence: 94%

“…It is conceivable that stress during this vulnerable time in cortical circuitry development increases apoptotic cell death of supernumerous interneurons, which is also at its peak during the second week of postnatal development (Blomgren et al, 2007 ; Schmid et al, 2013 ). Furthermore, we cannot exclude the possibility that PV immunoreactivity loss is caused by oxidative stress or neuroinflammation (Francis and Stevenson, 2011 ; Holland et al, 2014 ; Schmalbach et al, 2015 ; Marković et al, 2017 ). Our finding of decreased parvalbumin expression is consistent with the results of earlier studies showing reduced PV expression and cell density in the prefrontal cortex of the adolescent, but not adult (P100) rats (Francis and Stevenson, 2011 ; Wieck et al, 2013 ; Holland et al, 2014 ; Grassi-Oliveira et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

“…We used the P9 maternal deprivation model, as it has shown the strongest effects on behavior (Ellenbroek et al, 1998 ) when compared with earlier stress (at days 3 or 6). Additionally, this model has shown a strong impact on increasing oxidative stress in the brains of affected animals (Marković et al, 2017 ). Taken together, this MD protocol could be used to model some pathological features of schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

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Maternal Deprivation in Rats Decreases the Expression of Interneuron Markers in the Neocortex and Hippocampus

et al. 2021

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Early life stress has profound effects on the development of the central nervous system. We exposed 9-day-old rat pups to a 24 h maternal deprivation (MD) and sacrificed them as young adults (60-day-old), with the aim to study the effects of early stress on forebrain circuitry. We estimated numbers of various immunohistochemically defined interneuron subpopulations in several neocortical regions and in the hippocampus. MD rats showed reduced numbers of parvalbumin-expressing interneurons in the CA1 region of the hippocampus and in the prefrontal cortex, compared with controls. Numbers of reelin-expressing and calretinin-expressing interneurons were also reduced in the CA1 and CA3 hippocampal areas, but unaltered in the neocortex of MD rats. The number of calbinin-expressing interneurons in the neocortex was similar in the MD rats compared with controls. We analyzed cell death in 15-day-old rats after MD and found no difference compared to control rats. Thus, our results more likely reflect the downregulation of markers than the actual loss of interneurons. To investigate synaptic activity in the hippocampus we immunostained for glutamatergic and inhibitory vesicular transporters. The number of inhibitory synapses was decreased in the CA1 and CA3 regions of the hippocampus in MD rats, with the normal number of excitatory synapses. Our results indicate complex, cell type-specific, and region-specific alterations in the inhibitory circuitry induced by maternal deprivation. Such alterations may underlie symptoms of MD at the behavioral level and possibly contribute to mechanisms by which early life stress causes neuropsychiatric disorders, such as schizophrenia.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Maternal Deprivation in Rats Decreases the Expression of Interneuron Markers in the Neocortex and Hippocampus

et al. 2021

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“…Although interconnected with what is generally considered to be the stress response system centered on the hypothalamic-pituitary-adrenal axis, oxidative stress is a largely cellular process (Schiavone, Jaquet, Trabace, & Krause, 2013). Social stressors relevant to personality disorder, such as maternal deprivation, social defeat, and social deprivation, have been found to increase oxidative stress (Markovic et al, 2017;Schiavone et al, 2009;Solanki, Salvi, Patki, & Salim, 2017). We have previously found that impulsive aggression and the presence of personality disorder are both associated with increased oxidative stress, as evidenced by elevated blood levels of 8-hydroxy-2'-deoxyguanosine (8-OH-DG; Coccaro, Lee, & Gozal, 2016).…”

mentioning

confidence: 99%

Narcissistic and Borderline Personality Disorders: Relationship With Oxidative Stress

Lee

Gozal

Coccaro

et al. 2020

Journal of Personality Disorders

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The authors hypothesized that personality disorders characterized by interpersonal hypersensitivity would be associated with an elevated concentration of 8-hydroxy-2'-deoxyguanosine (8-OH-DG), the oxidized form of guanine, and a biomarker of oxidative stress burden. One hundred ninety-five male and female adults underwent semistructured diagnostic interviews, completed questionnaire measures of social cognition and emotional attribution, and had blood drawn for determination of plasma 8-OH-DG. A hierarchical linear regression model revealed that narcissistic and borderline personality disorders predicted 8-OH-DG level independently of the effects of age, gender, recent alcohol and cigarette use, current major depression, and posttraumatic stress disorder. In all subjects, 8-OH-DG level was also correlated with the number of borderline personality disorder symptoms present. Narcissistic and borderline personality disorders predicted oxidative stress burden independently of potentially confounding factors.

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“…Experimental models of early-life stress have already been associated with alterations on oxidative status and, thus, reported associations between altered mitochondrial respiratory chain, increased neuronal damage, decreased neuronal population in the hippocampus and impairments in spatial memory (Marković et al 2017;Noschang et al 2010;Zhu et al 2004). These impairments can be associated with the fact that the hippocampus is a susceptible region to both behavioral early life alterations and the effects of oxidative stress (Huang 2014;Salim 2017;Wang and Michaelis 2010;Youssef et al 2019).…”

Section: Introductionmentioning

confidence: 99%

Maternal separation induces long-term oxidative stress alterations and increases anxiety-like behavior of male Balb/cJ mice

et al. 2020

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Early life stress (ELS) exposure is a well-known risk factor for the development of psychiatric conditions, including anxiety disorder. Preclinical studies show that maternal separation (MS), a classical model of ELS, causes hypothalamic-pituitary-adrenal (HPA) axis alterations, a key contributor to the stress response modulation. Given that HPA axis activation has been shown to induce oxidative stress, it is possible to hypothesize that oxidative stress mediates the relationship between chronic ELS exposure and the development of several disorders. Here, we investigate the effects of MS in the oxidative status [plasma and brain reduced glutathione, catalase and thiobarbituric acid reactive substances (TBARS)], metabolism (glucose, triglycerides and cholesterol) and anxiety-like behaviors in adult Balb/cJ mice. In short, we found that MS increased anxiety-like behaviors in the open field, light/dark test but not in the elevated-plus maze. Animals also presented increased circulating cholesterol, increased TBARS in the plasma and decreased catalase in the hippocampus. Our findings suggest that MS induces long-term alterations in oxidative stress and increased anxiety-like behaviors.

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Long‐Term Effects of Maternal Deprivation on Redox Regulation in Rat Brain: Involvement of NADPH Oxidase

Cited by 14 publications

References 65 publications

Maternal Deprivation in Rats Decreases the Expression of Interneuron Markers in the Neocortex and Hippocampus

Maternal Deprivation in Rats Decreases the Expression of Interneuron Markers in the Neocortex and Hippocampus

Narcissistic and Borderline Personality Disorders: Relationship With Oxidative Stress

Maternal separation induces long-term oxidative stress alterations and increases anxiety-like behavior of male Balb/cJ mice

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