Sex-dependent mitophagy and neuronal death following rat neonatal hypoxia–ischemia

Demarest, Tyler G.; Waite, Eric L.; Kristián, Tibor; Puché, Adam C.; Waddell, Jaylyn; McKenna, Mary C.; Fiskum, Gary

doi:10.1016/j.neuroscience.2016.08.026

Cited by 48 publications

(36 citation statements)

References 54 publications

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“…Based on these results, it seems likely that our neonatal rat model of H/I injury corresponds well to the neonatal mouse model used in our previous study (Koike et al, 2008). Immunohistochemical and biochemical approaches for LC3 have shown that autophagy is involved in neuron death following H/I brain injury to neonatal rats when a hypoxic period is loaded for 120 min or more (Ginet et al, 2009;Liu et al, 2013;Carloni et al, 2014;Weis et al, 2014;Demarest et al, 2016;Xie et al, 2016). Moreover, the induction of autophagy is known to differ according to brain region (Weis et al, 2014) and dying pyramidal neurons in the hippocampal CA1 region exhibit strong apoptotic characteristics as opposed to autophagic neuron death (Ginet et al, 2009).…”

Section: Discussionsupporting

confidence: 70%

“…Recent studies on H/I brain injury using neonatal rats have focused on producing damage that was limited to the ipsilateral hemisphere via the use of a hypoxic period of 120 min or more (Ginet et al, 2009;Liu et al, 2013;Carloni et al, 2014;Weis et al, 2014;Demarest et al, 2016;Xie et al, 2016). The present study was an attempt to produce damage restricted to the ipsilateral hippocampus with a shorter hypoxic period: H/I injury produced by 60 min of hypoxia (Uchiyama et al, 2009).…”

Section: Discussionmentioning

confidence: 98%

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Induction of Autophagy in the Hippocampus after Hypoxic Ischemic Injury to Neonatal Rats

Koike

Kawahara

Shibata

et al. 2017

Archives of Histology and Cytology

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Summary. Neonatal hypoxic/ischemic (H/I) brain injury causes neurological impairment, including cognitive and motor dysfunction as well as seizures. Patterns of H/I injury-induced neuron death using rodent models are considered to be similar to the cases in human H/I encephalopathy. The participation of autophagy in neuron death has been a common feature in neonatal rodent models of H/I brain injury and human H/I encephalopathy when examined by immunochemical approaches for MAP1-LC3. This tendency has also been confirmed in neuronal tissue-specific Atg7 conditional knockout mice. However, while the current rat H/I model that is used for analyzing autophagy results in global damage to the ipsilateral hemisphere, it does not entirely reflect the neuropathological changes that appear in the neonatal mouse H/I model, in which the hippocampus is selectively damaged. The present study established a neonatal rat model of H/I injury with a milder ischemic insult, in which autophagy was involved in the hippocampal CA1 region after H/I injury when examined by electron microscopy, and by immunohistochemical and biochemical analyses of LC3.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 98%

Induction of Autophagy in the Hippocampus after Hypoxic Ischemic Injury to Neonatal Rats

Koike

Kawahara

Shibata

et al. 2017

Archives of Histology and Cytology

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“…For example, in the model of neonatal cerebral hypoxic‐ischaemia, it was reported that brain mitochondrial respiration was largely more decreased and oxidative stress more increased in 7‐day‐old male rat pups compared to female rat pups. The hormonal influence cannot explain these sex disparities because the level of circulating hormones was not different between males and females in this neonatal period …”

Section: Differences In Mitochondrial Metabolism After Strokementioning

confidence: 91%

Sex differences in brain mitochondrial metabolism: influence of endogenous steroids and stroke

Gaignard

Fréchou

Lière

et al. 2018

J Neuroendocrinology

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Steroids are neuroprotective and a growing body of evidence indicates that mitochondria are a potential target of their effects. The mitochondria are the site of cellular energy synthesis, regulate oxidative stress and play a key role in cell death after brain injury and neurodegenerative diseases. After providing a summary of the literature on the general functions of mitochondria and the effects of sex steroid administrations on mitochondrial metabolism, we summarise and discuss our recent findings concerning sex differences in brain mitochondrial function under physiological and pathological conditions. To analyse the influence of endogenous sex steroids, the oxidative phosphorylation system, mitochondrial oxidative stress and brain steroid levels were compared between male and female mice, either intact or gonadectomised. The results obtained show that females have higher a mitochondrial respiration and lower oxidative stress compared to males and also that these differences were suppressed by ovariectomy but not orchidectomy. We have also shown that the decrease in brain mitochondrial respiration induced by ischaemia/reperfusion is different according to sex. In both sexes, treatment with progesterone reduced the ischaemia/reperfusioninduced mitochondrial alterations. Our findings indicate sex differences in brain mitochondrial function under physiological conditions, as well as after stroke, and identify mitochondria as a target of the neuroprotective properties of progesterone. Thus, it is necessary to investigate sex specificity in brain physiopathological mechanisms, especially when mitochondria impairment is involved. K E Y W O R D Smitochondria, oxidative phosphorylation, oxidative stress, progesterone, sex difference, stroke | INTRODUCTIONThe main function of mitochondria is energy production. Mitochondria play a major role in the nervous system because neurones have a high metabolic rate and do not have a high capacity with respect to energy storage. Mitochondrial dysfunction has devastating consequences because mitochondria are centrally involved in neural cells life. Indeed, mitochondrial energy production is vital to maintain membrane potential in neurones. Mitochondria also play a major role in regulating oxidative stress and in death/survival cell signalling. They are also the site of the first steps of steroidogenesis and increasing evidence indicates that mitochondria are an essential target of the neuroactive effects of steroids, especially oestradiol and progesterone. In this review, we describe the sex differences and the role of sex steroids in brain mitochondrial energy production and oxidative stress. In particular, we summarise our recent work on brain mitochondrial metabolism in both sexes under physiological conditions, as well as after stroke, a pathology characterised by both sexual dimorphism and mitochondrial bioenergetics impairment. | MITOCHONDRIA ARE THE SITE OF ENERGY PRODUCTIONThe energy production by the mitochondria is mediated by three major enzymatic systems: the pyruva...

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“…In addition, this sex-specific adaptation to a stress is associated with a sex-specific expression of Lon protease isoform and proteolytic activity [76]. In mice subjected to hypoxia-ischemia, mitophagy induction is higher in females than in males and the lower clearance of damaged mitochondria in males may contribute to their greater vulnerability to neuronal death after hypoxia-ischemia [77]. Interestingly, the ERα-dependent UPRmt pathway is higher in females than in males [77, 78].…”

Section: Factors Affecting Mitochondrial Quality Controlmentioning

confidence: 99%

Mitophagy and Mitochondrial Quality Control Mechanisms in the Heart

Gottlieb¹,

Thomas²

2017

Curr Pathobiol Rep

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PURPOSE OF REVIEW Mitochondrial homeostasis and quality control are essential to maintenance of cardiac function and a disruption of this pathway can lead to deleterious cardiac consequences. RECENT FINDINGS Mitochondrial quality control has been described as a major homeostatic mechanism in cell. Recent studies highlighted that an impairment of mitochondrial quality control in different cell or mouse models is linked to cardiac dysfunction. Moreover, some conditions as aging, genetic mutations or obesity have been associated with mitochondrial quality control alteration leading to an accumulation of damaged mitochondria responsible for increased production of reactive oxygen species, metabolic inflexibility, and inflammation, all of which can have sustained effects on cardiac cell function and even cell death. SUMMARY In this review, we describe the major mechanisms of mitochondrial quality control, factors that can impair mitochondrial quality control, and the consequences of disrupted mitochondrial quality control.

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Sex-dependent mitophagy and neuronal death following rat neonatal hypoxia–ischemia

Cited by 48 publications

References 54 publications

<b>Induction of Autophagy in the Hippocampus after Hypoxic Ischemic Injury to Neonatal </b><b>Rats </b>

<b>Induction of Autophagy in the Hippocampus after Hypoxic Ischemic Injury to Neonatal </b><b>Rats </b>

Sex differences in brain mitochondrial metabolism: influence of endogenous steroids and stroke

Mitophagy and Mitochondrial Quality Control Mechanisms in the Heart

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