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
  • 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

    • br Materials and methods br Results and discussion

    2021-11-30


    Materials and methods
    Results and discussion
    Conclusion Altogether, our data provide an unexpected insight into Cx26 trafficking pathway and gap junction assembly in the cochlea. Since many of the disease-causing mutations in GJB2 impair the trafficking and delivery of Cx26 to the cell surface (Ambrosi et al., 2013; Hoang Dinh et al., 2009; Xu and Nicholson, 2013), our findings should help further research aimed to decipher the pathogenic significance of these mutations.
    Competing financial interests
    Acknowledgements We thank the GIGA-Cell Imaging platform. This work was supported by the Belgian Fonds de la Recherche Scientifique - FNRS.
    Introduction The cerebral cortex contains a multitude of blood vessels that regulate blood supply in response to local changes in a process known as functional hyperaemia. This process is characterised by an increase in neuronal activity followed by a rapid dilation of local blood vessels and hence increased blood supply providing oxygen and glucose necessary for cellular function. Functional hyperaemia is controlled through the process of neurovascular coupling (NVC). This process involves an intercellular communication system based on ion exchange through pumps and channels between neurons, astrocytes (glial cells), vascular cells, and the extracellular space (ECS) (Attwell, Buchan, Charpak, Lauritzen, MacVicar, Newman, 2010, Drewes, 2012, Hamel, 2006, Iadecola, 2004). Together these communicating cells comprise a neurovascular unit (NVU). Impaired functional hyperaemia resulting in reduced blood supply to tosylate tissue is associated with various pathologies such as cortical spreading depression (CSD) (Girouard, Iadecola, 2006, Lauritzen, Dreier, Fabricius, Hartings, Graf, Strong, 2011, Pietrobon, Moskowitz, 2014). CSD is the occurrence of slowly propagating waves of high extracellular potassium (K) concentration (over  mM) and neuronal depolarisation in the gray matter of various species (Leâo, 1944). It typically arises in metabolically compromised tissue as in ischemia (Dreier, 2011) and is associated with several neurological disorders such as migraine, subarachnoid and intracranial haemorrhage, Alzheimers disease, stroke, and hypertension (Charles, Baca, 2013, Girouard, Iadecola, 2006, Lauritzen, Dreier, Fabricius, Hartings, Graf, Strong, 2011, Takano, Nedergaard, 2009). Cell damage or death during ischemia results in reduced supply of oxygen and glucose to brain cells (Huguet et al., 2016). This decreases adenosine triphosphate (ATP) production and leads to the failure of the neuronal Na/K ATPase pump, which in turn leads to increased extracellular K levels, elevated neuronal sodium (NA) concentration, cell swelling, and neuronal depolarisation (Enger et al., 2015). In these conditions we often observe a decrease in cerebral blood flow followed by a slight increase and slow return to the baseline (Chen, Feng, Li, Jacques, Zeng, Luo, 2006, Tomita, Tomita, Schiszler, Amano, Tanahashi, Kobari, Takeda, Ohtomo, Fukuuchi, 2002). Indeed, numerous studies have documented that small increases in extracellular K concentration can lead to vasodilation, whereas high concentrations lead to vasoconstriction (Cameron, Caronna, 1976, Edwards, Hirst, Silverberg, 1988, Golding, Steenberg, Johnson, Bryan, 2000, Kuschinsky, Wahl, Bosse, Thurau, 1972, McCarron, Halpern, 1990). The massive rise in extracellular K to levels sufficient for depolarising adjacent cells is the main factor for allowing the spread of depolarisation throughout the tissue (Ayata, Lauritzen, 2015, Enger, Tang, Vindedal, Jensen, Johannes Helm, Sprengel, Looger, Nagelhus, 2015). These waves of depolarisation are then followed by a short period of neuronal inactivity. Pathologies such as CSD can occur when the normal regulation of extracellular K fails (Wallraff, 2006). Astrocytes are able to regulate the extracellular K concentration via a process known as spatial buffering. Astrocytes can take up K via ion channels and distribute it further to neighbouring astrocytes via gap junctions. The neuroprotective role of astrocytic gap junctions during diseased states has been under debate (see Chen and Swanson (2003); Chew et al. (2010) for review). Some studies indicate that gap junction communication may increase ischemic damage by allowing the propagation of pre-apoptotic signals between dying and viable astrocytes (Lin et al., 1998). On the other hand, Nakase et al. (2003) demonstrated that reduced expression of Cx43 in astrocytes leads to a significant increase in the size of ischemic infarcts, suggesting that gap junctions play a critical role in the regulation and removal of ions. Ma et al. (2016) demonstrated both experimentally and numerically that a syncytium of coupled astrocytes can distribute excess K and maintain a physiological membrane potential in the presence of elevated extracellular K concentration.