Ucp2 Induced by Natural Birth Regulates Neuronal Differentiation of the Hippocampus and Related Adult Behavior

Simon-Areces, Julia; Dietrich, Marcelo O.; Hermes, Gretchen; Garcia-Segura, Luis Miguel; Arévalo, María Ángeles; Horváth, Tamas L.

doi:10.1371/journal.pone.0042911

Cited by 54 publications

(32 citation statements)

References 20 publications

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“…In support of the notion that mtROS transients (and not sustained elevated ROS levels) mediate the benefits of exercise on integrative physiology, UCP2 was found crucial to support exercise-induced synaptogenesis in the dentate gyrus of the hippocampal formation, a key site of spatial learning (Dietrich et al, 2008). This same mechanism is also relevant to hippocampal development (Simon-Areces et al, 2012) and lifespan determination (Andrews and Horvath, 2009). …”

Section: Mitochondrial Ros and Exercisementioning

confidence: 97%

Mitochondrial ROS Signaling in Organismal Homeostasis

Shadel

Horváth

2015

Cell

932

601

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Summary Generation, transformation, and utilization of organic molecules in support of cellular differentiation, growth, and maintenance are basic tenets that define life. In eukaryotes, mitochondrial oxygen consumption plays a central role in these processes. During the process of oxidative phosphorylation, mitochondria utilize oxygen to generate ATP from organic fuel molecules but in the process also produce reactive oxygen species (ROS). While ROS have long been appreciated for their damage-promoting, detrimental effects, there is now a greater understanding of their roles as signaling molecules. Here, we review mitochondrial ROS-mediated signaling pathways with an emphasis on how they are involved in various basal and adaptive physiological responses that control organismal homeostasis.

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Section: Mitochondrial Ros and Exercisementioning

confidence: 97%

Mitochondrial ROS Signaling in Organismal Homeostasis

Shadel

Horváth

2015

Cell

932

601

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“…Mitochondrial, cytoplasmic and nuclei-enriched fractions were obtained using an adaptation of a previously published differential centrifugation protocol (Simon-Areces et al, 2012). Sample lysates were obtained using a Teflon pestle in ice-cold IM homogenization buffer 20 mM Tris HCl, 10 mM KOAc, 1 mM EDTA, 0.25% NP40, containing freshly added 1 mM dithiothreitol (DTT) and a proteinase and phosphatase inhibitor cocktail (Complete EDTAfree, Roche Diagnostics GmbH, Rotkreuz, Switzerland).…”

Section: Protein Extraction and Quantificationmentioning

confidence: 99%

Social deficits induced by peripubertal stress in rats are reversed by resveratrol

Poirier

Imamura

Zanoletti

et al. 2014

Journal of Psychiatric Research

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a b s t r a c tAdolescence is increasingly recognized as a critical period for the development of the social system, through the maturation of social competences and of their underlying neural circuitries. The present study sought to test the utility of resveratrol, a dietary phenol recently reported to have mood lifting properties, in modulating social interaction that is deficient following early life adversity. The main aims were to 1) pharmacologically restore normative social investigation levels dampened by peripubertal stress in rats and 2) identify neural pathways engaged by this pharmacological approach. Following peripubertal (P28e42) stress consisting of unpredictable exposures to fearful experiences, at adulthood the subjects' propensity for social exploration was examined in the three-chamber apparatus, comparing time invested in social or non-social investigation. Administered intraperitoneally 30 min before testing, resveratrol (20 mg/kg) normalized the peripubertal stress-induced social investigation deficit seen in the vehicle group, selectively altering juvenile but not object exploration. Examination of prefrontal cortex subregion protein samples following acute resveratrol treatment in a separate cohort revealed that while monoamine oxidase A (MAOA) enzymatic activity remained unaltered, nuclear AKT activation was selectively increased in the infralimbic cortex, but not in the prelimbic or anterior cingulate cortex. In contrast, androgen receptor nuclear localization was increased in the prelimbic cortex, but not in the infralimbic or anterior cingulate cortex. This demonstration that social contact deficits are reversed by resveratrol administration emphasizes a prosocial role for this dietary phenol, and evokes the possibility of developing new treatments for social dysfunctions.

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“…UCP-2 is considered to be a neuroprotective factor7273 that is overexpressed during oxidative stress or after brain injuries747576, contributing to decrease the production of ROS in the mitochondria77. Interestingly, UCP-2 expression increases in the mice brain after vaginal birth23, supporting the idea of vaginal birth as a mild hypoxic insult for the brain. In our experiments, UCP-2 expression was higher in males than in females as a consequence of the perinatal testosterone peak, possibly meaning that the nervous tissue from males needs a higher protection against oxidative stress than in females.…”

Section: Discussionmentioning

confidence: 90%

Developmental Sex Differences in the Metabolism of Cardiolipin in Mouse Cerebral Cortex Mitochondria

Acaz‐Fonseca

Ortiz-Rodriguez

López-Rodríguez

et al. 2017

Sci Rep

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Cardiolipin (CL) is a mitochondrial-specific phospholipid. CL content and acyl chain composition are crucial for energy production. Given that estradiol induces CL synthesis in neurons, we aimed to assess CL metabolism in the cerebral cortex (CC) of male and female mice during early postnatal life, when sex steroids induce sex-dimorphic maturation of the brain. Despite the fact that total amount of CL was similar, its fatty acid composition differed between males and females at birth. In males, CL was more mature (lower saturation ratio) and the expression of the enzymes involved in synthetic and remodeling pathways was higher, compared to females. Importantly, the sex differences found in CL metabolism were due to the testosterone peak that male mice experience perinatally. These changes were associated with a higher expression of UCP-2 and its activators in the CC of males. Overall, our results suggest that the perinatal testosterone surge in male mice regulates CL biosynthesis and remodeling in the CC, inducing a sex-dimorphic fatty acid composition. In male’s CC, CL is more susceptible to peroxidation, likely explaining the testosterone-dependent induction of neuroprotective molecules such as UCP-2. These differences may account for the sex-dependent mitochondrial susceptibility after perinatal hypoxia/ischemia.

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Ucp2 Induced by Natural Birth Regulates Neuronal Differentiation of the Hippocampus and Related Adult Behavior

Cited by 54 publications

References 20 publications

Mitochondrial ROS Signaling in Organismal Homeostasis

Mitochondrial ROS Signaling in Organismal Homeostasis

Social deficits induced by peripubertal stress in rats are reversed by resveratrol

Developmental Sex Differences in the Metabolism of Cardiolipin in Mouse Cerebral Cortex Mitochondria

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