Archives

  • 2018-07
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • Recent studies have shown that the

    2021-06-11

    Recent studies have shown that the extracellular regulated protein kinase 1 and 2 (ERK1 and ERK2), commonly referred to collectively as Calmidazolium chloride sale ERK 1/2, are members of the mitogen-activated protein kinase (MAPK) family. This family of kinases transport signals from the surface of the cell to the nucleus, thereby mediating the activation of nuclear transcription factors that participate in cell apoptosis and other biological functions (Cargnello and Roux, 2011; Ciccarelli and Giustetto, 2014). ERK 1/2, and their phosphorylations (p-ERK 1/2) play a notable role in neurobehavioral responses and cognitive processes that include learning and memory (Johnson and Lapadat, 2002). In addition, di-(2-ethylhexyl) phthalate, a homologue of DBP, can induce excessive reactive oxygen species (ROS) and cause calcium aggravation in hepatocytes, which were isolated from the liver of male albino rats of the Wistar strain weighing approximately 120–130 g (4 weeks of age), exposed to DEHP for 24 h at doses of 5, 10, 25, 50, 100, and 200 μM (Ghosh et al., 2010). But even more importantly, intracellular ROS accumulation and a Ca2+ imbalance can activate the ERK 1/2 pathways in hippocampal Calmidazolium chloride sale (Mccubrey et al., 2006; Kemmerling et al., 2007). On the basis of there being a possible relationship between DBP and the ERK 1/2 pathway, we conducted this research to determine whether DBP induces hippocampal neuron apoptosis and whether it increases the observed behavioral disorders via the ERK 1/2 pathway. We examined the ROS, GSH and MDA content to evaluate oxidative stress. The levels of CaM, CaMK II and PKC were examined to assess the Ca2+ signaling pathway. We determined ERK 1/2 and ERK 1/2 pathway-related proteins (sensitive biomarkers) including BDNF and p-CREB levels after DBP treatment to study the role of ERK 1/2 in DBP-mediated effects. The levels of cyto C, caspase-3 and TNF-α were also analysised to evaluate apoptosis in hippocampal neurons. We also looked for changes in mouse behavior, and observed histopathological changes and immunohistochemistry in the hippocampus. In addtion, we used the antioxidant VE and the DHP Ca2+ antagonist, NMDP, to demonstrate that the ERK 1/2 pathway mediates oxidative stress and the Ca2+ signaling pathway induced by DBP. Although this study is an animal experiment, it still provides a better understanding of the possible mechanism by which neurotoxic environmental pollutants induce LDs in children.
    Materials and methods
    Results
    Discussion Apoptosis plays a major role in the development of neurons, and a defect in the apoptosis process may underly various neurodevelopmental disorders (Xia et al., 1995; Mattson, 2000). Hippocampal neuron apoptosis also plays a significant role in the development of LD (Hoffman, 2004; Whitlock et al., 2006). The hippocampus is an essential structure in the limbic system of the brain, and is closely related to learning, memory and cognitive function (Whitlock et al., 2006). Studies have shown that the hippocampus is mainly composed of CA1, CA2, CA3 and DG, and that these areas may be affected, which tends to pathological changes (Remondes and Schuman, 2004; Tonegawa et al., 2018). DBP, a ubiquitous environmental contaminant with potential cerebral neurotoxicity, can act on the hippocampus, since it is able to cross the blood-brain and placental barriers (Wójtowicz et al., 2017). The brain is a metabolically active organ, which incessantly generates free radicals (ROS) during the metabolic process (Uttara et al., 2009). A certain level of ROS is necessary for maintaining normal life activities, but excessive ROS can change cell functions and cause adverse effects. ROS accumulation can cause oxidative damage and even apoptosis of cells (Saeidnia and Abdollahi, 2013). Studies in vivo and in vitro have shown that oxidative stress is usually regarded as an upstream molecular event of an exogenous stimulus signal, and thus plays an important role in the neurotoxicity mediated by DBP (Li et al., 2010; Ma et al., 2015). The imbalance between the production of ROS and the antioxidant defense can lead to oxidative stress, which in turn causes cells to be damaged by ROS. Oxidative stress can lead to GSH depletion, MDA production, membrane damage, breaks in DNA strands, and the activation of proteases, nucleic acids and protein kinases (Finkel and Holbrook, 2000). According to our results, the hippocampi of the mice in the 50 mg/kg/day DBP group were shown to have a significantly higher oxidative stress level, suggesting that the excessive production of intracellular ROS induced by DBP could lead to further oxidative damage of the hippocampus. Suematsu et al. (2003) reported that ROS may be associated with a variety of signal transduction pathways, which can induce cell apoptosis or necrosis, and may eventually lead to organ dysfunction such as the hypofunction of learning and memory, and to cognitive impairment.