CD44 Transmembrane Receptor and Hyaluronan Regulate Adult Hippocampal Neural Stem Cell Quiescence and Differentiation
| Autor: | Kerstin Feistel, Weiping Su, Reid H.J. Olsen, Summer F. Acevedo, Scott Foster, Rubing Xing, Jacob Raber, Larry S. Sherman |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Neurogenesis Hippocampus Hippocampal formation Biology Biochemistry Subgranular zone Mice 03 medical and health sciences Neural Stem Cells Neurobiology medicine Animals Hyaluronic Acid Receptor Molecular Biology Cells Cultured Cellular Senescence reproductive and urinary physiology CD44 Wild type Cell Biology Neural stem cell nervous system diseases Cell biology Hyaluronan Receptors 030104 developmental biology medicine.anatomical_structure nervous system Immunology biology.protein Female biological phenomena cell phenomena and immunity Gene Deletion |
| Zdroj: | Journal of Biological Chemistry. 292:4434-4445 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m116.774109 |
| Popis: | Adult neurogenesis in the hippocampal subgranular zone (SGZ) is involved in learning and memory throughout life but declines with aging. Mice lacking the CD44 transmembrane receptor for the glycosaminoglycan hyaluronan (HA) demonstrate a number of neurological disturbances including hippocampal memory deficits, implicating CD44 in the processes underlying hippocampal memory encoding, storage, or retrieval. Here, we found that HA and CD44 play important roles in regulating adult neurogenesis, and we provide evidence that HA contributes to age-related reductions in neural stem cell (NSC) expansion and differentiation in the hippocampus. CD44-expressing NSCs isolated from the mouse SGZ are self-renewing and capable of differentiating into neurons, astrocytes, and oligodendrocytes. Mice lacking CD44 demonstrate increases in NSC proliferation in the SGZ. This increased proliferation is also observed in NSCs grown in vitro, suggesting that CD44 functions to regulate NSC proliferation in a cell-autonomous manner. HA is synthesized by NSCs and increases in the SGZ with aging. Treating wild type but not CD44-null NSCs with HA inhibits NSC proliferation. HA digestion in wild type NSC cultures or in the SGZ induces increased NSC proliferation, and CD44-null as well as HA-disrupted wild type NSCs demonstrate delayed neuronal differentiation. HA therefore signals through CD44 to regulate NSC quiescence and differentiation, and HA accumulation in the SGZ may contribute to reductions in neurogenesis that are linked to age-related decline in spatial memory. |
| Databáze: | OpenAIRE |
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