Amelioration of oxidative stress-induced phenotype loss of parvalbumin interneurons might contribute to the beneficial effects of environmental enrichment in a rat model of post-traumatic stress disorder

Sun, Xiao Ru; Zhang, Hui; Zhao, Hong; Ji, Mu; Li, Hui H.; Wu, Jing; Li, Kuan Y.; Yang, Jian

doi:10.1016/j.bbr.2016.06.016

Cited by 38 publications

(28 citation statements)

References 36 publications

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“…Similarly, hippocampal PV GABAergic interneurons have been implicated in anxiety and social behaviors (Çalışkan et al, ; Sun et al, ; Wöhr et al, ). Activation of these neurons in the vHip of mice induced anxiolytic effects in the EPM and impaired social behavior (Zou et al, ), while PV KO mice have been shown to display significant deficits in social interaction and serve as a model for autism spectrum disorders (Wöhr et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Activation of these neurons in the vHip of mice induced anxiolytic effects in the EPM and impaired social behavior (Zou et al, 2016), while PV KO mice have been shown to display significant deficits in social interaction and serve as a model for autism spectrum disorders (Wöhr et al, 2015). Moreover, a rat model of PTSD displayed anxiety-like behavior in the EPM and LOF, accompanied by significant decreases in glutamic acid decarboxylase (GAD)-67, a marker of GABAergic neurons, and PV immunoreactivity (Sun et al, 2016). In the current study, we have shown that a population of vHip RXFP3 mRNA-expressing neurons coexpresses PV mRNA.…”

Section: Discussionmentioning

confidence: 99%

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Chronic activation of the relaxin‐3 receptor on GABA neurons in rat ventral hippocampus promotes anxiety and social avoidance

et al. 2019

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Anxiety disorders are highly prevalent in modern society and better treatments are required. Key brain areas and signaling systems underlying anxiety include prefrontal cortex, hippocampus, and amygdala, and monoaminergic and peptidergic systems, respectively. Hindbrain GABAergic projection neurons that express the peptide, relaxin‐3, broadly innervate the forebrain, particularly the septum and hippocampus, and relaxin‐3 acts via a Gi/o‐protein‐coupled receptor known as the relaxin‐family peptide 3 receptor (RXFP3). Thus, relaxin‐3/RXFP3 signaling is implicated in modulation of arousal, motivation, mood, memory, and anxiety. Ventral hippocampus (vHip) is central to affective and cognitive processing and displays a high density of relaxin‐3‐positive nerve fibers and RXFP3 binding sites, but the identity of target neurons and associated effects on behavior are unknown. Therefore, in adult, male rats, we assessed the neurochemical nature of hippocampal RXFP3 mRNA‐expressing neurons and anxiety‐like and social behavior following chronic RXFP3 activation in vHip by viral vector expression of an RXFP3‐selective agonist peptide, R3/I5. RXFP3 mRNA detected by fluorescent in situ hybridization was topographically distributed across the hippocampus in somatostatin‐ and parvalbumin‐mRNA expressing GABA neurons. Chronic RXFP3 activation in vHip increased anxiety‐like behavior in the light–dark box and elevated‐plus maze, but not the large open‐field test, and reduced social interaction with a conspecific stranger. Our data reveal disruptive effects of persistent RXFP3 signaling on hippocampal GABA networks important in anxiety; and identify a potential therapeutic target for anxiety disorders that warrants further investigation in relevant preclinical models.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Chronic activation of the relaxin‐3 receptor on GABA neurons in rat ventral hippocampus promotes anxiety and social avoidance

et al. 2019

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“…The upregulation of NOX2 expression after stress suggests an increase of the prooxidative activity in rats exposed to CMS. Increased levels of NOX2 have also been observed in brain areas of animals exposed to prolonged social isolation from weaning (Schiavone et al 2009) as well as in a model of posttraumatic stress disorder, where NOX2 upregulation was paralleled by a decrease of PVB expression (Sun et al, 2016). Considering that NOX2 has been reported as the primary phagocytic oxidase (Bermudez et al, 2016), its altered expression may be associated with the increased activity of microglial cells under stressful conditions.…”

Section: Discussionmentioning

confidence: 99%

Chronic Stress Exposure Reduces Parvalbumin Expression in the Rat Hippocampus through an Imbalance of Redox Mechanisms: Restorative Effect of the Antipsychotic Lurasidone

Rossetti

Paladini

Colombo

et al. 2018

International Journal of Neuropsychopharmacology

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BackgroundPsychiatric disorders are associated with altered function of inhibitory neurotransmission within the limbic system, which may be due to the vulnerability of selective neuronal subtypes to challenging environmental conditions, such as stress. In this context, parvalbumin-positive GABAergic interneurons, which are critically involved in processing complex cognitive tasks, are particularly vulnerable to stress exposure, an effect that may be the consequence of dysregulated redox mechanisms.MethodsAdult Male Wistar rats were subjected to the chronic mild stress procedure for 7 weeks. After 2 weeks, both control and stress groups were further divided into matched subgroups to receive chronic administration of vehicle or lurasidone (3 mg/kg/d) for the subsequent 5 weeks. Using real-time RT-PCR and western blot, we investigated the expression of GABAergic interneuron markers and the levels of key mediators of the oxidative balance in the dorsal and ventral hippocampus.ResultsChronic mild stress induced a specific decrease of parvalbumin expression in the dorsal hippocampus, an effect normalized by lurasidone treatment. Interestingly, the regulation of parvalbumin levels was correlated to the modulation of the antioxidant master regulator NRF2 and its chaperon protein KEAP1, which were also modulated by pharmacological intervention.ConclusionsOur findings suggest that the susceptibility of parvalbumin neurons to stress may represent a key mechanism contributing to functional and structural impairments in specific brain regions relevant for psychiatric disorders. Moreover, we provide new insights on the mechanism of action of lurasidone, demonstrating that its chronic treatment normalizes chronic mild stress-induced parvalbumin alterations, possibly by potentiating antioxidant mechanisms, which may ameliorate specific functions that are deteriorated in psychiatric patients.

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“…EE prevented the increase in reactive oxygen species (ROS) levels, thiobarbituric acid reactive substances (TBARS) and the superoxide dismutase (SOD) activity induced by chronic cerebral hypoperfusion in rats (Cechetti et al, 2012). Another study that investigated free radical levels through 8-hydroxy-2-deoxyguanosine (8-OH-dG), a marker of oxidative stress associated with DNA, reported that EE attenuated the upregulation induced by inescapable foot shocks in the hippocampus and prefrontal cortex of rats (Sun et al, 2016). Zebrafish exposure to chronic stress alters behavior and increases cortisol levels.…”

Section: Introductionmentioning

confidence: 99%

Environmental enrichment modulates the response to chronic stress in zebrafish

Marcon

Mocelin

Benvenutti

et al. 2018

Journal of Experimental Biology

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Several studies have shown that manipulations to the housing environment modulate susceptibility to stress in laboratory animals, mainly in rodents. Environmental enrichment (EE) is one such manipulation that promotes neuroprotection and neurogenesis, besides affecting behaviors such as drug self-administration. Zebrafish are a popular and useful animal model for behavioral neuroscience studies; however, studies evaluating the impact of housing conditions in this species are scarce. In this study, we verified the effects of EE on behavioral (novel tank test) and biochemical [cortisol and reactive oxygen species (ROS)] parameters in zebrafish submitted to unpredictable chronic stress (UCS). Consistent with our previous findings, UCS increased anxiety-like behavior, cortisol and ROS levels in zebrafish. EE for 21 or 28 days attenuated the effects induced by UCS on behavior and cortisol, and prevented the effects on ROS levels. Our findings reinforce the idea that EE exerts neuromodulatory effects across species, reducing vulnerability to stress and its biochemical impact. Also, these results indicate that zebrafish is a suitable model animal to study the behavioral effects and neurobiological mechanisms related to EE.

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Amelioration of oxidative stress-induced phenotype loss of parvalbumin interneurons might contribute to the beneficial effects of environmental enrichment in a rat model of post-traumatic stress disorder

Cited by 38 publications

References 36 publications

Chronic activation of the relaxin‐3 receptor on GABA neurons in rat ventral hippocampus promotes anxiety and social avoidance

Chronic activation of the relaxin‐3 receptor on GABA neurons in rat ventral hippocampus promotes anxiety and social avoidance

Chronic Stress Exposure Reduces Parvalbumin Expression in the Rat Hippocampus through an Imbalance of Redox Mechanisms: Restorative Effect of the Antipsychotic Lurasidone

Environmental enrichment modulates the response to chronic stress in zebrafish

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