The adult human subventricular zone: partial ependymal coverage and proliferative capacity of cerebrospinal fluid

Sophia F A M de Sonnaville; Miriam E van Strien; Jinte Middeldorp; Jacqueline A Sluijs; Simone A van den Berge; Martina Moeton; Vanessa Donega; Annemiek van Berkel; Tasmin Deering; Lidia De Filippis; Angelo L Vescovi; Eleonora Aronica; Rainer Glass; Wilma D J van de Berg; Dick F Swaab; Pierre A Robe; Elly M Hol

doi:10.1093/braincomms/fcaa150

The adult human subventricular zone: partial ependymal coverage and proliferative capacity of cerebrospinal fluid

Brain Commun. 2020 Oct 13;2(2):fcaa150. doi: 10.1093/braincomms/fcaa150. eCollection 2020.

Authors

Sophia F A M de Sonnaville¹, Miriam E van Strien¹, Jinte Middeldorp¹, Jacqueline A Sluijs¹, Simone A van den Berge², Martina Moeton², Vanessa Donega¹, Annemiek van Berkel¹, Tasmin Deering¹, Lidia De Filippis³, Angelo L Vescovi³, Eleonora Aronica⁴, Rainer Glass⁵, Wilma D J van de Berg⁶, Dick F Swaab⁷, Pierre A Robe⁸, Elly M Hol¹

Affiliations

¹ Department of Translational Neuroscience, UMC Utrecht Brain Centre, University Medical Centre Utrecht, University Utrecht, Utrecht, The Netherlands.
² Department of Neuroimmunology, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
³ Department of Regenerative Medicine, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
⁴ Department of (Neuro)pathology, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
⁵ Department of Neurosurgical Research, Clinic for Neurosurgery, Ludwig Maximilian University of Munich, Munich, Germany.
⁶ Department of Anatomy and Neurosciences, Section Clinical Neuroanatomy, Amsterdam University Medical Centre, Location VU, Amsterdam, The Netherlands.
⁷ Department of Neuropsychiatric Disorders, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
⁸ Department of Neurosurgery, UMC Utrecht Brain Centre, University Medical Centre Utrecht, University Utrecht, Utrecht, The Netherlands.

Abstract

Neurogenesis continues throughout adulthood in specialized regions of the brain. One of these regions is the subventricular zone. During brain development, neurogenesis is regulated by a complex interplay of intrinsic and extrinsic cues that control stem-cell survival, renewal and cell lineage specification. Cerebrospinal fluid (CSF) is an integral part of the neurogenic niche in development as it is in direct contact with radial glial cells, and it is important in regulating proliferation and migration. Yet, the effect of CSF on neural stem cells in the subventricular zone of the adult human brain is unknown. We hypothesized a persistent stimulating effect of ventricular CSF on neural stem cells in adulthood, based on the literature, describing bulging accumulations of subventricular cells where CSF is in direct contact with the subventricular zone. Here, we show by immunohistochemistry on post-mortem adult human subventricular zone sections that neural stem cells are in close contact with CSF via protrusions through both intact and incomplete ependymal layers. We are the first to systematically quantify subventricular glial nodules denuded of ependyma and consisting of proliferating neural stem and progenitor cells, and showed that they are present from foetal age until adulthood. Neurosphere, cell motility and differentiation assays as well as analyses of RNA expression were used to assess the effects of CSF of adult humans on primary neural stem cells and a human immortalized neural stem cell line. We show that human ventricular CSF increases proliferation and decreases motility of neural stem cells. Our results also indicate that adult CSF pushes neural stem cells from a relative quiescent to a more active state and promotes neuronal over astrocytic lineage differentiation. Thus, CSF continues to stimulate neural stem cells throughout aging.

Keywords: cerebrospinal fluid; glial nodules; human; neural stem cells; subventricular zone.