Highly aggressive behavior induced by social stress is associated to reduced cytochrome c oxidase activity in mice brain cortex

Mendonça, Ana Paula M.; Hoppe, Luanda Yanaan; Gaviraghi, A.; Araújo-Jorge, Tânia C.; Oliveira, Gabriel Melo de; Felippe, Renata Machado; Oliveira, Marcus F.; Fragoso, Viviane Muniz da Silva

doi:10.1016/j.neuint.2019.03.017

Cited by 7 publications

(7 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, recent studies using a mouse model in which the mitochondrial protein UCP2 was ablated specifically within microglia demonstrated male-specific alterations in synaptic architecture and neural functions (Yasumoto et al, 2021), suggesting a link between microglial mitochondrial function and synaptic regulation. These data build upon other findings that mitochondrial dysfunction and altered metabolism play a critical role in the regulation of social behaviors (Kanellopoulos et al, 2020; Miranda Mendonça et al, 2019; Picard et al, 2018), suggesting that altered microglial mitochondrial function may regulate the establishment of complex social behaviors through alterations in synaptic regulation. Previous studies have demonstrated that microglial phagocytosis regulates the development of synaptic circuitry important for social behavior in the ACC during the time period surrounding our PN9 injection (Block et al, 2022).…”

Section: Limitations Of the Studysupporting

confidence: 81%

“…Importantly, mitochondrial respiratory function is critical for the regulation of microglial homeostatic and inflammatory processes and is impaired following lipopolysaccharide (LPS)-mediated proinflammatory activation (Bernier et al, 2020b; Nair et al, 2019; Orihuela et al, 2016; York et al, 2020). Social behavioral changes may also be regulated by dysfunctional mitochondrial metabolism (Kanellopoulos et al, 2020; Miranda Mendonça et al, 2019; Picard et al, 2018). Mitochondrial metabolism was identified as the key molecular mechanism underlying changes in social behaviors in the CYFIP1 knockout fly model of neurodevelopmental disorders (Kanellopoulos et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Gonadal Hormones Impart Male-Biased Behavioral Vulnerabilities to Immune Activation via Microglial Mitochondrial Function

Bordt

Moya

et al. 2022

Preprint

View full text Add to dashboard Cite

There is a strong male bias in the prevalence of many neurodevelopmental disorders such as autism spectrum disorder. However, the mechanisms underlying this sex bias remain elusive. Infection during the perinatal period is associated with an increased risk of neurodevelopmental disorder development. Here, we used a mouse model of early-life immune activation that reliably induces deficits in social behaviors only in males. We demonstrate that male-biased alterations in social behavior are dependent upon microglial immune signaling and are coupled to alterations in mitochondrial morphology, gene expression, and function specifically within microglia, the innate immune cells of the brain. Additionally, we show that this behavioral and microglial mitochondrial vulnerability to early-life immune activation is programmed by the male-typical perinatal gonadal hormone surge. These findings demonstrate that social behavior in males over the lifespan are regulated by microglia-specific mechanisms that are shaped by events that occur in early development.

show abstract

Section: Limitations Of the Studysupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Gonadal Hormones Impart Male-Biased Behavioral Vulnerabilities to Immune Activation via Microglial Mitochondrial Function

Bordt

Moya

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…CRF is involved in the activation of the hypothalamus-pituitary-adrenal axis (HPA axis), whose activation is the main adaptive response to stress carried out by animals and humans, culminating in the release of corticosterone in animals and cortisol in humans (Czerniczyniec et al, 2007). In a recent study, our team evaluated the activity of the mitochondrial respiratory chain in the brains of animals subjected to the MSA, and we observed that in the cortex of AgR mice, the activity of the enzyme cytochrome c oxidase (COX), the important complex IV of the respiratory chain, was reduced by 43% (Mendonça et al, 2019). We know that the reduction of mitochondrial activity can promote changes in the production of reactive oxygen species (ROS) (Phull et al, 2018;Ryan et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Experimental Social Stress: Dopaminergic Receptors, Oxidative Stress, and c-Fos Protein Are Involved in Highly Aggressive Behavior

Felippe

Oliveira

Barbosa

et al. 2021

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Aggression is defined as hostile behavior that results in psychological damage, injury and even death among individuals. When aggression presents itself in an exacerbated and constant way, it can be considered escalating or pathological. The association between social stress and the emergence of exacerbated aggressiveness is common and is suggested to be interconnected through very complex neurobiological factors. For example, alterations in the expression of the dopaminergic receptors D1 and D2, reactive oxygen species (ROS) and the c-Fos protein in the cortex have been observed. Our objective was to analyze which factors are involved at the neurobiological level in the highly aggressive response of Swiss Webster adult male mice in a vivarium. In this work, we investigated the relationship among dopaminergic receptors, the production of ROS and the expression of c-Fos. Mice with exacerbated aggression were identified by the model of spontaneous aggression (MSA) based on the grouping of young mice and the regrouping of the same animals in adulthood. During the regrouping, we observed different categories of behavior resulting from social stress, such as (i) highly aggressive animals, (ii) defeated animals, and (iii) harmonic groups. To evaluate the dopaminergic system and the c-Fos protein, we quantified the expression of D1 and D2 dopaminergic receptors by Western blotting and fluorescence immunohistochemistry and that of the c-Fos protein by fluorescence immunohistochemistry. The possible production of ROS was also evaluated through the dihydroethidium (DHE) assay. The results showed that aggressive and subordinate mice showed a reduction in the expression of the D1 receptor, and no significant difference in the expression of the D2 receptor was observed between the groups. In addition, aggressive mice exhibited increased production of ROS and c-Fos protein. Based on our results, we suggest that exacerbated aggression is associated with social stress, dysregulation of the dopaminergic system and exacerbated ROS production, which leads to a state of cellular oxidative stress. The overexpression of c-Fos due to social stress suggests an attempt by the cell to produce antioxidant agents to reduce the toxic cellular concentration of ROS.

show abstract

“…Reducing the activity of OXPHOS was positively correlated with aggressive behavior in honey bees [ 65 , 66 ]. In mice, aggressive behavior resulting from social stress would selectively reduce COX expression and activity, compromising energy demand, with consequence for cognition and behavior [ 67 ]. According to the GSEA result, OXPHOS has a high NES value in the TGS2, TGS4, and TGS6 groups (different from honey bees and mice).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analyses Provide Insights into the Aggressive Behavior toward Conspecific and Heterospecific in Thitarodes xiaojinensis (Lepidoptera: Hepialidae)

Rao

Cao

et al. 2021

Insects

View full text Add to dashboard Cite

Aggressive behavior in animals is important for survival and reproduction. It is well studied in adult insects, such as flies, ants, honey bees, and crickets. However, the larvae of Lepidopteran insects are also aggressive, studies of which are still lacking. Here, RNA-seq was used to generate a high-quality database for the aggressive behavior of Thitarodes xiaojinensis toward conspecifics and heterospecifics. Although there was similar aggressive behavior between the conspecific group and heterospecific group, significant differences were identified at the transcriptional level. When there was aggressive behavior toward conspecifics, T. xiaojinensis trended toward higher expression at the respiratory chain, while cuticle development and metabolism may have interfered. On the other hand, when there was aggressive behavior toward H. armigera, genes related to neuron and cuticle development, cellular processes, and its regulated signaling pathways were significantly upregulated, while the genes associated with oxidation-reduction and metabolism were downregulated. Weighted gene co-expression networks analysis (WGCNA) was performed, and two modules with properties correlating to the aggressive behavior of T. xiaojinensis were identified. Several hub genes were predicted and confirmed by qRT-PCR, such as CLTC, MYH, IGF2BP1, and EMC. This study provides a global view and potential key genes for the aggressive behavior of T. xiaojinensis toward conspecifics and heterospecifics. Further investigation of the hub genes would help us to better understand the aggressive behavior of insects.

show abstract

Highly aggressive behavior induced by social stress is associated to reduced cytochrome c oxidase activity in mice brain cortex

Cited by 7 publications

References 50 publications

Gonadal Hormones Impart Male-Biased Behavioral Vulnerabilities to Immune Activation via Microglial Mitochondrial Function

Gonadal Hormones Impart Male-Biased Behavioral Vulnerabilities to Immune Activation via Microglial Mitochondrial Function

Experimental Social Stress: Dopaminergic Receptors, Oxidative Stress, and c-Fos Protein Are Involved in Highly Aggressive Behavior

Transcriptome Analyses Provide Insights into the Aggressive Behavior toward Conspecific and Heterospecific in Thitarodes xiaojinensis (Lepidoptera: Hepialidae)

Contact Info

Product

Resources

About