Short- and long-term treatment with modafinil differentially affects adult hippocampal neurogenesis
| Autor: | A. Storch, E. Ellwardt, M.D. Brandt |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
drug effects [Dentate Gyrus]
medicine.medical_specialty Neurogenesis Modafinil drug effects [Neurogenesis] Hippocampal formation Biology Mice physiology [Dentate Gyrus] Precursor cell Internal medicine medicine Animals drug effects [Neurons] pharmacology [Benzhydryl Compounds] ddc:610 Benzhydryl Compounds Progenitor cell Cell Proliferation Neurons drug effects [Cell Proliferation] Cell growth Stem Cells General Neuroscience Dentate gyrus metabolism [Bromodeoxyuridine] metabolism [Dentate Gyrus] drug effects [Stem Cells] Mice Inbred C57BL Endocrinology Bromodeoxyuridine metabolism [Neurons] Dentate Gyrus Female Calretinin Neuroscience medicine.drug |
| Zdroj: | Neuroscience 278, 267-275 (2014). doi:10.1016/j.neuroscience.2014.08.014 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/j.neuroscience.2014.08.014 |
| Popis: | The generation of new neurons in the dentate gyrus of the adult brain has been demonstrated in many species including humans and is suggested to have functional relevance for learning and memory. The wake promoting drug modafinil has popularly been categorized as a so-called neuroenhancer due to its positive effects on cognition. We here show that short- and long-term treatment with modafinil differentially effects hippocampal neurogenesis. We used different thymidine analogs (5-bromo-2-deoxyuridine (BrdU), chlorodeoxyuridine (CldU), iododeoxyuridine (IdU)) and labeling protocols to investigate distinct regulative events during hippocampal neurogenesis, namely cell proliferation and survival. Eight-week-old mice that were treated with modafinil (64 mg/kg, i.p.) every 24 h for 4 days show increased proliferation in the dentate gyrus indicated by BrdU-labeling and more newborn granule cells 3 weeks after treatment. Short-term treatment for 4 days also enhanced the number of postmitotic calretinin-expressing progenitor cells that were labeled with BrdU 1 week prior to treatment indicating an increased survival of new born immature granule cells. Interestingly, long-term treatment for 14 days resulted in an increased number of newborn Prox1 + granule cells, but we could not detect an additive effect of the prolonged treatment on proliferation and survival of newborn cells. Moreover, daily administration for 14 days did not influence the number of proliferating cells in the dentate gyrus. Together, modafinil has an acute impact on precursor cell proliferation as well as survival but loses this ability during longer treatment durations. |
| Databáze: | OpenAIRE |
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