bims-stacyt Biomed news
on Paracrine crosstalk between cancer and the organism
Issue of 2018‒10‒07
two papers selected by
Cristina Muñoz Pinedo
L’Institut d’Investigació Biomèdica de Bellvitge

  1. Neuroscience. 2018 Sep 26. pii: S0306-4522(18)30622-5. [Epub ahead of print]
    Yang X, Zhong M, Chen J, Li T, Cheng Q, Dai Y.
      Neonatal hypoxic-ischemic brain damage (HIBD) is a cerebral hypoxic-ischemic disease caused by a variety of insults during the perinatal period, leading to varying degrees of cognitive dysfunction. Mesenchymal stem cells play an important role in functional recovery, but the mechanism is not yet clear. It has been reported that HIF-1<alpha> and PTEN are involved in the process of hypoxia-ischemia, but the specific roles that these proteins play remains to be understood. In this study, we performed oxygen glucose deprivation (OGD) or CoCl2 preconditioning on hippocampal neurons to simulate an hypoxic environment in vitro, and then co-cultured them with BMSCs, to observe the effect of BMSCs and the role of HIF-1<alpha>. In addition, bpV, an inhibitor of PTEN was added to OGD neurons to determine the role of PTEN during hypoxia. We found that the levels of cell damage and apoptosis in OGD neurons decreased significantly after co-culture with BMSCs. Apoptosis was increased when HIF-1<alpha> was inhibited, but neurons remained protected when PTEN was suppressed. We further established that HIF-1<alpha> was enriched at the PTEN promoter both in BMSCs and hippocampal neurons, with increased enrichment under hypoxic conditions, leading to reduced transcription of PTEN. Our findings support the conclusion that CoCl2 preconditioning of BMSCs can simulate hypoxic conditions and can protect OGD neurons, an effect that is mediated through activation of the HIF-1<alpha> system and repression of PTEN transcription.
    Keywords:  Bone mesenchymal stem cells; Hypoxia-inducible factor-1α; Hypoxic-ischemic brain damage; Phosphatase and tensin homologue deleted on chromosome ten
  2. Neurochem Int. 2018 Sep 26. pii: S0197-0186(18)30367-X. [Epub ahead of print]
    Song M, Ahn JH, Kim H, Kim DW, Lee TK, Lee JC, Kim YM, Lee CH, Hwang IK, Yan BC, Won MH, Park JH.
      Recent studies have shown that obesity and its related metabolic dysfunction exacerbate outcomes of ischemic brain injuries in some brain areas, such as the hippocampus and cerebral cortex when they are subjected to transient ischemia. However, the impact of obesity in the striatum after brief transient ischemia has not yet been addressed. The objective of this study was to investigate effects of obesity on neuronal damage and inflammation in the striatum after transient ischemia and to examine the role of mTOR which is involved in the pathogenesis of metabolic and neurological diseases. Gerbils were fed with normal diet (ND) or high-fat diet (HFD) for 12 weeks and subjected to 5 min of transient ischemia. HFD-fed gerbils showed significant increase in body weight, blood glucose level, serum triglycerides, total cholesterol and low-density lipoprotein cholesterol without affecting food intake. Neuronal death/loss in the HFD-fed gerbils occurred in the dorsolateral striatum 2 days after transient ischemia, and neuronal loss was increased 5 days after transient ischemia, although no neuronal loss was observed in ND-fed gerbils at any time after transient ischemia. The HFD-fed gerbils showed hypertrophied microglia and further increased expressions of tumor necrosis factor-alpha, interukin-1beta, mammalian target of rapamycin (mTOR) and phosphorylated-mTOR during pre- and post-ischemic phases compared with the ND-fed gerbils. Additionally, we found that treatment with mTOR inhibitor rapamycin in the HFD-fed gerbils significantly attenuated transient ischemia-induced neuronal death in the dorsolateral striatum. These findings reveal that chronic HFD-induced obesity results in severe neuroinflammation and significant increase of mTOR activation, which could contribute to neuronal death in the stratum following 5 min of transient ischemia. Especially, abnormal mTOR activation would play a key role in mediating obesity-induced severe ischemic brain injury.
    Keywords:  Ischemia-reperfusion; Neuroinflammation; Neuronal loss/death; Obesity; Pro-inflammatory cytokines; mTOR