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 55 publications

(34 citation statements)

References 20 publications

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“…Overexpression of UCP2 also rescued diminished pro-survival markers such as Bcl-2, cyclin G2, and HSP90 [27]. Furthermore, UCP2 has been documented to be neuroprotective via its involvement in neurogenesis and synaptogenesis, suggesting a role in neuronal growth and development [53, 54]. Future studies are needed to explore the potential roles of UCP2 in our cerebral ischemic model.…”

Section: Discussionmentioning

confidence: 99%

Disrupted mitochondrial genes and inflammation following stroke

et al. 2016

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Aims Determine the subacute time course of mitochondria disruption, cell death, and inflammation in a rat model of unilateral motor cortical ischemic stroke. Main Methods Rats received unilateral ischemia of the motor cortex and were tested on behavioral tasks to determine impairments. Animals were euthanized at 24 h, 72 h and 144 h and mRNA expression of key mitochondria proteins and indicators of inflammation, apoptosis and potential regenerative processes in ipsilesion cortex and striatum, using RT-qPCR. Mitochondrial proteins were examined at 144 h using immunoblot analysis. Key Findings Rats with stroke induced-behavioral deficits had sustained, 144 h post-lesion, decreases in mitochondrial-encoded electron transport chain proteins NADH dehydrogenase subunit-1 and cytochrome c oxidase subunit-1 (mRNA and protein) and mitochondrial DNA content in perilesion motor and sensory cortex. Uncoupling-protein-2 gene expression, but not superoxide dismutase-2, remained elevated in ipsilateral cortex and striatum at this time. Cortical inflammatory cytokine, interleukin-6, was increased early and was followed by increased macrophage marker F4/80 after stroke. Cleaved caspase-3 activation was elevated in cortex and growth associated protein-43 was elevated in the cortex and striatum six days post-lesion. Significance We identified a relationship between three disrupted pathways, (1) sustained loss of mitochondrial proteins and mitochondrial DNA copy number in the cortex linked to decreased mitochondrial gene transcription; (2) early inflammatory response mediated by interleukin- 6 followed by macrophages; (3) apoptosis in conjunction with the activation of regenerative pathways. The stroke-induced spatial and temporal profiles lay the foundation to target pharmacological therapeutics to these three pathways.

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Section: Discussionmentioning

confidence: 99%

Disrupted mitochondrial genes and inflammation following stroke

et al. 2016

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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

1,011

670

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

Cited by 55 publications

References 20 publications

Disrupted mitochondrial genes and inflammation following stroke

Disrupted mitochondrial genes and inflammation following stroke

Mitochondrial ROS Signaling in Organismal Homeostasis

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

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