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Cereb Cortex. 2019 Jan 3. doi: 10.1093/cercor/bhy284. [Epub ahead of print]

Nestin Regulates Neurogenesis in Mice Through Notch Signaling From Astrocytes to Neural Stem Cells.

Author information

1
Laboratory of Astrocyte Biology and CNS Regeneration, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
2
Faculty of Science and Engineering, Biosciences, Åbo Akademi University, Turku, Finland.
3
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
4
Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
5
Celica BIOMEDICAL, Ljubljana, Slovenia.
6
Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia.
7
Laboratory of Regenerative Neuroimmunology, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
8
Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.
9
University of Newcastle, Newcastle, NSW, Australia.

Abstract

The intermediate filament (nanofilament) protein nestin is a marker of neural stem cells, but its role in neurogenesis, including adult neurogenesis, remains unclear. Here, we investigated the role of nestin in neurogenesis in adult nestin-deficient (Nes-/-) mice. We found that the proliferation of Nes-/- neural stem cells was not altered, but neurogenesis in the hippocampal dentate gyrus of Nes-/- mice was increased. Surprisingly, the proneurogenic effect of nestin deficiency was mediated by its function in the astrocyte niche. Through its role in Notch signaling from astrocytes to neural stem cells, nestin negatively regulates neuronal differentiation and survival; however, its expression in neural stem cells is not required for normal neurogenesis. In behavioral studies, nestin deficiency in mice did not affect associative learning but was associated with impaired long-term memory.

PMID:
30605503
DOI:
10.1093/cercor/bhy284

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