Skip to main content
PMC home page
Frontiers in Molecular Neuroscience logoLink to Frontiers in Molecular Neuroscience
editorial
. 2018 Oct 31;11:407. doi: 10.3389/fnmol.2018.00407

Editorial: Neuroglia Molecular Mechanisms in Psychiatric Disorders

Caterina Scuderi 1,*, Mami Noda 2, Alexei Verkhratsky 3,4,5
PMCID: PMC6220059  PMID: 30429774

Neuroglia are an extended class of cells of ectodermal (astroglia, oligodendroglia, and peripheral glial cells) and mesodermal (microglia) origin, which provide extensive homeostatic support, protection, and defense of nervous tissue (Kettenmann and Ransom, 2013; Verkhratsky and Butt, 2013; Verkhratsky and Nedergaard, 2018). Pathological potential of glial cells has been recognized since their discovery (Virchow, 1858; Andriezen, 1893; Nissl, 1899; Alzheimer, 1910), while recent decade highlighted the fundamental role of neuroglia in the progression of all types of neurological diseases (Giaume et al., 2007; Verkhratsky et al., 2013, 2014, 2016, 2017; Burda and Sofroniew, 2014; Sofroniew, 2014; Zeidan-Chulia et al., 2014; Burda et al., 2016; Pekny et al., 2016; Verkhratsky and Parpura, 2016; Ferrer, 2018). The neurogliopathology is complex and is represented by glial reactivity (activation of microglia, astrogliosis) or glial degeneration, atrophy, and loss of functions. In particular glial cells undergo prominent changes in the context of neuropsychiatric diseases; these changes are generally represented by loss and asthenia of astroglia and oligodendroglia in conjunction with microglial activation (Rajkowska and Stockmeier, 2013; Verkhratsky et al., 2015; Cobb et al., 2016; Rajkowska et al., 2018). In this research topic we addressed the contribution of neuroglia to major neuropsychiatric conditions including major depression, schizophrenia, and alcohol use disorders.

The gliocentric theory of major depression has been overviewed by Czéh and Nagy who presented recent findings on glial structural and functional abnormalities at molecular and cellular levels. Subsequently they focused on clinical studies and summarized neuroimaging as well as post-mortem molecular and histopathological evidence supporting leading role of glia in the progression of depression and related mood disorders. Notably, the depression is associated with substantial loss of macroglial cells with loss of their function, in conjunction with microglial activation, which summarily affect neuronal networks and brain function. Structural and molecular alterations of astrocytes and oligodendrocytes also lie at the core of alcohol use disorders (Miguel-Hidalgo). In particular alcohol exposure, as well as alcohol withdrawal affects glial transporters, glutamate (GABA) glutamine shuttle and gap junctions, which connect glial syncytia. The association of endothelial cells, blood-brain barrier and neurovascular unit with neuropsychiatric diseases has been discussed by Malik and Di Benedetto, who presented evidence supporting pathophysiological role of disrupted erythropoietin-producing-hepatocellular carcinoma receptors (EphR)/Ephrin signaling cascades.

Pathophysiological changes in microglia in context of environmental stress associated with neurodevelopmental and neuropsychiatric disorders are overviewed by Tay et al. In particular, they discuss the role of microglia in Nasu-Hakola disease, hereditary diffuse leukoencephaly with spheroids, Rett syndrome, autism spectrum disorders, obsessive-compulsive disorder and major psychiatric pathologies such as addiction, major depressive disorder, bipolar disorder, schizophrenia, eating disorders, and sleep disorders. Studies on humans have demonstrated neuroinflammation and microglial reactivity in patients with schizophrenia as well as in animal models. In the latter, the gender differences have been also described (Hui et al.); and it turned out that in males prominent differences in microglial distribution, morphology, and microglial activation may account for higher incidence of schizophrenia. Up-regulation of microglia associated genes following administration of IgG-Saporin has been demonstrated to alter a memory-associated behavior (Dobryakova et al.). The role of microglial activation and phagocytosis in Parkinson's disease and therapeutic potential of targeting microglia were reviewed by Janda et al. Of note both asphyxia and cesarean section are associated with the expression of Schizophrenia risk genes (Paparelli et al.). The link between neuregulin and β-secretase with schizophrenia is shown by Zhang et al.

Glial cells can be targets for specific therapy. Effects of electro-acupuncture on hippocampal neuroinflamamtion in rat depressed model (induced by unpredictable stress-induced depressive- and anxiety-like behavior) are presented by Yue et al. They showed that treatment with acupuncture reduce behavioral abnormalities and abrogate neuroinflammation. Quercitin neuroprotection was discussed by Gao et al.

All in all, the papers assembled in this Research Topic provide a wide picture of the importance of neuroglia in the pathogenesis of neuropsychiatric diseases and discuss possible therapeutic strategies aimed at glial cells.

Author contributions

CS, MN, and AV wrote the editorial. All authors read and approved the submitted version.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

  1. Alzheimer A. (1910). Beiträge zur Kenntnis der pathologischen Neuroglia und ihrer Beziehungen zu den Abbauvorgängen im Nervengewebe, in Histologische und histopathologische Arbeiten über die Grosshirnrinde mit besonderer Berücksichtigung der pathologischen Anatomie der Geisteskrankheiten, Vol. 3, eds Nissl F., Alzheimer A. (Jena: Gustav Fischer; ), 401–562. [Google Scholar]
  2. Andriezen W. L. (1893). The neuroglia elements of the brain. Brit. Med. J. 2, 227–230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burda J. E., Bernstein A. M., Sofroniew M. V. (2016). Astrocyte roles in traumatic brain injury. Exp. Neurol. 275(Pt 3), 305–315. 10.1016/j.expneurol.2015.03.020 [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burda J. E., Sofroniew M. V. (2014). Reactive gliosis and the multicellular response to CNS damage and disease. Neuron 81, 229–248. 10.1016/j.neuron.2013.12.034 [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cobb J. A., O'Neill K., Milner J., Mahajan G. J., Lawrence T. J., May W. L., et al. (2016). Density of GFAP-immunoreactive astrocytes is decreased in left hippocampi in major depressive disorder. Neuroscience 316, 209–220. 10.1016/j.neuroscience.2015.12.044 [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ferrer I. (2018). Astrogliopathy in Tauopathies. Neuroglia 1, 126–150. 10.3390/neuroglia1010010 [DOI] [Google Scholar]
  7. Giaume C., Kirchhoff F., Matute C., Reichenbach A., Verkhratsky A. (2007). Glia: the fulcrum of brain diseases. Cell Death Differ. 14, 1324–1335. 10.1038/sj.cdd.4402144 [DOI] [PubMed] [Google Scholar]
  8. Kettenmann H., Ransom B. R. (2013). Neuroglia. Oxford: Oxford University Press. [Google Scholar]
  9. Nissl F. (1899). Ueber einige Beziehungen zwischen Nervenzellerkrankungen und Erscheinungen bei verschiedenen Psychosen. Arch. Psychiatr. 32, 1–21. [Google Scholar]
  10. Pekny M., Pekna M., Messing A., Steinhäuser C., Lee J. M., Parpura V., et al. (2016). Astrocytes: a central element in neurological diseases. Acta Neuropathol. 131, 323–345. 10.1007/s00401-015-1513-1 [DOI] [PubMed] [Google Scholar]
  11. Rajkowska G., Legutko B., Moulana M., Syed M., Romero D. G., Stockmeier C. A., et al. (2018). Astrocyte pathology in the ventral prefrontal white matter in depression. J. Psychiatr. Res. 102, 150–158. 10.1016/j.jpsychires.2018.04.005 [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Rajkowska G., Stockmeier C. A. (2013). Astrocyte pathology in major depressive disorder: insights from human postmortem brain tissue. Curr. Drug Targets 14, 1225–1236. 10.2174/13894501113149990156 [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sofroniew M. V. (2014). Multiple roles for astrocytes as effectors of cytokines and inflammatory mediators. Neuroscientist. 20:160–172. 10.1177/1073858413504466 [DOI] [PubMed] [Google Scholar]
  14. Verkhratsky A., Butt A. M. (2013). Glial Physiology and Pathophysiology. Chichester: Wiley-Blackwell, 560. [Google Scholar]
  15. Verkhratsky A., Marutle A., Rodríguez-Arellano J. J., Nordberg A. (2015). Glial asthenia and functional paralysis: a new perspective on neurodegeneration and alzheimer's disease. Neuroscientist 21, 552–568. 10.1177/1073858414547132 [DOI] [PubMed] [Google Scholar]
  16. Verkhratsky A., Nedergaard M. (2018). Physiology of astroglia. Physiol. Rev. 98, 239–389. 10.1152/physrev.00042.2016 [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Verkhratsky A., Parpura V. (2016). Astrogliopathology in neurological, neurodevelopmental and psychiatric disorders. Neurobiol. Dis. 85, 254–261. 10.1016/j.nbd.2015.03.025 [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Verkhratsky A., Parpura V., Pekna M., Pekny M., Sofroniew M. (2014). Glia in the pathogenesis of neurodegenerative diseases. Biochem. Soc. Trans. 42, 1291–1301. 10.1042/BST20140107 [DOI] [PubMed] [Google Scholar]
  19. Verkhratsky A., Rodríguez J. J., Parpura V. (2013). Astroglia in neurological diseases. Future Neurol. 8, 149–158. 10.2217/fnl.12.90 [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Verkhratsky A., Steardo L., Parpura V., Montana V. (2016). Translational potential of astrocytes in brain disorders. Prog. Neurobiol. 144, 188–205. 10.1016/j.pneurobio.2015.09.003 [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Verkhratsky A., Zorec R., Parpura V. (2017). Stratification of astrocytes in healthy and diseased brain. Brain Pathol. 27, 629–644. 10.1111/bpa.12537 [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Virchow R. (1858). Die Cellularpathologie in ihrer Begründung auf Physiologische and Pathologische Gewebelehre. Zwanzig Vorlesungen gehalten während der Monate Februar, März und April 1858 im Pathologischen Institut zu Berlin. Berlin: Hirschwald, 440. [Google Scholar]
  23. Zeidan-Chulia F., Salmina A. B., Malinovskaya N. A., Noda M., Verkhratsky A., Moreira J. C. (2014). The glial perspective of autism spectrum disorders. Neurosci. Biobehav. Rev. 38, 160–172. 10.1016/j.neubiorev.2013.11.008 [DOI] [PubMed] [Google Scholar]

Articles from Frontiers in Molecular Neuroscience are provided here courtesy of Frontiers Media SA

RESOURCES