Social Isolation Stress-Induced Oxidative Damage in Mouse Brain and Its Modulation by Majonoside-R2, a Vietnamese Ginseng Saponin

Hương, Nguyêñ Thị Thu; Murakami, Yukihisa; Tohda, Michihisa; Watanabe, Hiroshi; Matsumoto, Kinzo

doi:10.1248/bpb.28.1389

Cited by 40 publications

(25 citation statements)

References 39 publications

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“…As described in Introduction, both Hk and gsts1 have been implicated in ROS metabolisms (Singh et al, 2001; Weng et al, 2006; Ueda & Wu, 2008). A potential role of ROS in mediating social isolation-induced phenomena has been inferred from increased ROS levels in mouse brain (Huong et al, 2005) and urine (Miyashita et al, 2006) after social isolation. Interestingly, recent independent studies have demonstrated the involvement of a cytochrome p450 gene, a potential player in ROS regulation, in Drosophila male-male aggression (Dierick & Greenspan 2006).…”

Section: Discussionmentioning

confidence: 99%

Effects of Social Isolation on Neuromuscular Excitability and Aggressive Behaviors inDrosophila: Altered Responses byHkandgsts1, Two Mutations Implicated in Redox Regulation

Ueda

2009

Journal of Neurogenetics

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Social deprivation is known to trigger a variety of behavioral and physiological modifications in animal species but the underlying genetic and cellular mechanisms are not fully understood. As we described previously, adult female flies reared in isolation show increased frequency of aggressive behaviors than those reared in group. Here we report that isolated rearing also caused significantly altered nerve and muscle excitability and enhanced synaptic transmission at larval neuromuscular junctions. We found that mutations of two genes, Hyperkinetic (Hk) and glutathione S-transferase-S1 (gsts1) alter the response to social isolation in Drosophila. Hk and gsts1 mutations increased adult female aggression and larval neuromuscular hyperexcitability even when reared in group. Unlike wild type, these behavioral and electrophysiological phenotypes were not further enhanced in these mutants by isolated rearing. Products of these two genes have been implicated in reactive oxygen species (ROS) metabolism. We previously reported in these mutants increased signals from a ROS probe at larval neuromuscular junctions and this study revealed distinct effects of isolation rearing on these mutants compared to the control larvae in ROS-probe signals. Our data further demonstrated modified nerve and muscle excitability by a reducing agent, dithiothreitol. Our results suggest that altered cellular ROS regulation can exert pleiotropic effects on nerve, synapse, and muscle functions and may involve different redox mechanisms in different cell types to modify behavioral expressions. Therefore, ROS regulation may take part in the cellular responses to social isolation stress, underlying an important form of neural and behavioral plasticity.

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Section: Discussionmentioning

confidence: 99%

Effects of Social Isolation on Neuromuscular Excitability and Aggressive Behaviors inDrosophila: Altered Responses byHkandgsts1, Two Mutations Implicated in Redox Regulation

Ueda

2009

Journal of Neurogenetics

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“…Nulliparous animals that would become the “maternal” group were housed with breeder hsd:ICR males for a 2 weeks mating period, while those in the “virgin” control group were housed with age-matched female littermates to provide comparable levels of social interaction. While it has been shown that the effects of individual vs. group housing on stress levels in female mice can be variable among mouse strains (Arndt et al, 2009), multiple studies suggest that ICR males are healthier and less stressed when housed in groups (Ben-Nathan and Feuerstein, 1990; Huong et al, 2005; Kabuki et al, 2009), and group housed ICR females housed alone are more susceptible to virus-induced mortality (Ben-Nathan et al, 1991, 1995). After the mating period, all females from both groups were housed individually through parturition (post-partum day 0) until tissue collection (post-partum day 7).…”

Section: Methodsmentioning

confidence: 99%

Medial prefrontal cortex: genes linked to bipolar disorder and schizophrenia have altered expression in the highly social maternal phenotype

Eisinger

Driessen

Zhao

et al. 2014

Front. Behav. Neurosci.

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The transition to motherhood involves CNS changes that modify sociability and affective state. However, these changes also put females at risk for post-partum depression and psychosis, which impairs parenting abilities and adversely affects children. Thus, changes in expression and interactions in a core subset of genes may be critical for emergence of a healthy maternal phenotype, but inappropriate changes of the same genes could put women at risk for post-partum disorders. This study evaluated microarray gene expression changes in medial prefrontal cortex (mPFC), a region implicated in both maternal behavior and psychiatric disorders. Post-partum mice were compared to virgin controls housed with females and isolated for identical durations. Using the Modular Single-set Enrichment Test (MSET), we found that the genetic landscape of maternal mPFC bears statistical similarity to gene databases associated with schizophrenia (5 of 5 sets) and bipolar disorder (BPD, 3 of 3 sets). In contrast to previous studies of maternal lateral septum (LS) and medial preoptic area (MPOA), enrichment of autism and depression-linked genes was not significant (2 of 9 sets, 0 of 4 sets). Among genes linked to multiple disorders were fatty acid binding protein 7 (Fabp7), glutamate metabotropic receptor 3 (Grm3), platelet derived growth factor, beta polypeptide (Pdgfrb), and nuclear receptor subfamily 1, group D, member 1 (Nr1d1). RT-qPCR confirmed these gene changes as well as FMS-like tyrosine kinase 1 (Flt1) and proenkephalin (Penk). Systems-level methods revealed involvement of developmental gene networks in establishing the maternal phenotype and indirectly suggested a role for numerous microRNAs and transcription factors in mediating expression changes. Together, this study suggests that a subset of genes involved in shaping the healthy maternal brain may also be dysregulated in mental health disorders and put females at risk for post-partum psychosis with aspects of schizophrenia and BPD.

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“…7,27,36). Similarly, elevated concentrations of NOx have been observed in the brain under stress conditions (25,39). In the testis, it has been proposed that NO is involved in the regulation of T biosynthesis by Leydig cells under normal (15,42,58) and stress conditions (29 -31).…”

Section: In the Present Investigation Wt And Inosmentioning

confidence: 97%

Testosterone production in mice lacking inducible nitric oxide synthase expression is sensitive to restraint stress

Weissman¹,

Sottas²,

Zhou³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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Weissman BA, Sottas CM, Zhou P, Iadecola C, Hardy MP. Testosterone production in mice lacking inducible nitric oxide synthase expression is sensitive to restraint stress. Am J Physiol Endocrinol Metab 292: E615-E620, 2007. First published October 10, 2006; doi:10.1152/ajpendo.00412.2006.-Immobilization stress (IMO) induces a rapid increase in glucocorticoid secretion [in rodents, corticosterone CORT)] and this is associated with decreased circulating testosterone (T) levels. Nitric oxide (NO), a reactive free radical and neurotransmitter, has been reported to be produced at higher rates in tissues such as brain during stress. The biosynthesis of T is also known to be dramatically suppressed by NO. Specifically, the inducible isoform of nitric oxide synthase (iNOS) was directly implicated in this suppression. To assess the respective roles of CORT and NO in stress-mediated inhibition of T production, adult wild-type (WT) and inducible nitric oxide synthase knockout (iNOS Ϫ/Ϫ ) male mice were evaluated. Animals of each genotype were assigned to either basal control or 3-h IMO groups. Basal plasma and testicular T levels were equivalent in both genotypes, whereas testicular weights of mutant mice were significantly higher compared with WT animals. Exposure to 3-h IMO increased plasma CORT and decreased T concentrations in mice of both genotypes. Testicular T levels were also affected by stress in WT and mutant males, being sharply reduced in both genotypes. However, the concentrations of nitrite and nitrate, the stable metabolites of NO measured in testicular extracts, did not differ between control and stressed WT and iNOS Ϫ/Ϫ mice. These results support the hypothesis that CORT, but not NO, is a plausible candidate to mediate rapid stress-induced suppression of Leydig cell steroidogenesis.

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Social Isolation Stress-Induced Oxidative Damage in Mouse Brain and Its Modulation by Majonoside-R2, a Vietnamese Ginseng Saponin

Cited by 40 publications

References 39 publications

Effects of Social Isolation on Neuromuscular Excitability and Aggressive Behaviors inDrosophila: Altered Responses byHkandgsts1, Two Mutations Implicated in Redox Regulation

Effects of Social Isolation on Neuromuscular Excitability and Aggressive Behaviors inDrosophila: Altered Responses byHkandgsts1, Two Mutations Implicated in Redox Regulation

Medial prefrontal cortex: genes linked to bipolar disorder and schizophrenia have altered expression in the highly social maternal phenotype

Testosterone production in mice lacking inducible nitric oxide synthase expression is sensitive to restraint stress

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