Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 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
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • 2024-04

    • Epidemiological evidence indicates that neuroinflammation pl

    2022-05-13

    Epidemiological evidence indicates that neuroinflammation plays a pivotal role in pathogenesis of AD (Heneka et al., 2015, Heneka et al., 2013, Holmes et al., 2009, Liu et al., 2016). For example, prolonged treatment with nonsteroidal anti-inflammatory drugs reduces the risk of developing AD (In et al., 2001, Sastre et al., 2003, Weggen et al., 2001). Synaptic plasticity is particularly sensitive to IL-1β as this cytokine can disrupt formation of dendritic spines (Heneka et al., 2015). In this study, we found that Aβ1-42 oligomers significantly increased secretion of IL-1β, TNF-α, and IL-6 by astrocytes and neurons. These results suggest that the pathogenesis of AD may be correlated with increased levels of these inflammatory mediators produced by astrocytes and neurons. Previous studies have shown that several inflammatory mediators appear to disrupt glutamate homeostasis, in part, by down-regulating expression or function of high-affinity EAATs (Boycott et al., 2008, Ronnback and Hansson, 2004, Sitcheran et al., 2005, Yan et al., 2014). These results suggest that inflammatory mediators may be involved in impairment of glutamate uptake. However, additional work will be required to sufficiently characterize whether Aβ alters expression or function of EAATs through signaling cascade effects of proinflammatory cytokines. In conclusion, we demonstrated that Aβ1-42 oligomers attenuated glutamate uptake in astrocytes and decreased astrocytic GLT-1 and GLAST protein expression. Furthermore, Aβ1-42 oligomers also decreased glutamate uptake in neurons. These impaired processes may lead to excess glutamate in the synaptic cleft and neuronal cell death because of excitotoxicity. Our present findings offer further evidence that EAATs-related expression and dysfunction may be important features of AD pathology and suggest that pharmacological interference aimed at enhancing astrocytic and neuronal glutamate uptake may open a new therapeutic opportunity to treat AD.
    Conflict of interests
    Introduction Intracerebral hemorrhage (ICH) is a serious subtype of stroke characterized by extravasations of blood into MK-4827 Racemate mg parenchyma resulting in high mortality and morbidity rates (Qureshi et al., 2009). The hematoma formation produces a transient ischemic effect that ultimately leads to increased levels of extracellular glutamate and further excitotoxicity, oxidative stress and neuronal cell death (Hu et al., 2016; Prabhakaran and Naidech, 2012; Righy et al., 2016; Wagner, 2007; Wu et al., 2013). The extension of hemorrhage and brain edema are key variables responsible for the development of these mechanisms and are the main determinants of neurologic deterioration (Lim-Hing and Rincon, 2017). Glutamate is an excitatory neurotransmitter that plays an important role in the pathogenesis of neuronal injury; it has been implicated in a number of brain disorders such as stroke, traumatic brain injury, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson disease and Huntington's disease (Amorini et al., 2017; Bi et al., 2017; Lewerenz and Maher, 2015; Qureshi et al., 2003). Glial glutamate transporters 1 (EAAT1) and 2 (EAAT2) are the essential proteins controlling the glutamate reuptake to maintain extracellular glutamate concentrations below neurotoxic levels (López-Bayghen and Ortega, 2011; Martinez-Lozada et al., 2016; Rothstein et al., 1996). Although the changes of glutamate uptake, EAAT1 and EAAT2 have been widely reported in the ischemic condition (Hu et al., 2017; Rao et al., 2001; Yatomi et al., 2013), studies of experimental intracerebral hemorrhage are scarce (Qureshi et al., 2003). Moreover, there are conflicting results of EAAT1 and EAAT2 and of glutamate uptake depending of brain injury and site of lesion (Dumont et al., 2014; Piao et al., 2015). It is now recognized that astrocytic glutamate transporters may have differential expression patterns and act depending of specific transcriptional regulators (Martinez-Lozada et al., 2016). Additionally, the injury effect on Na+/K+-ATPase and glutamine synthetase (GS) activities can also contribute to distinguish patterns of EAAT1/2. Previous studies have demonstrated a direct relationship between both enzyme (Na+/K+-ATPase and GS) activities and the glial glutamate transporters, EAAT1 and EAAT2 (Genda et al., 2011; Lehmann et al., 2009; Zou et al., 2010). Thus, the knowledge of these parameters may help understand the pathogenesis of hemorrhagic stroke.