title: Protracted brain development in a rodent model of extreme longevity.
abstract: Extreme longevity requires the continuous and large-scale adaptation of organ systems to delay senescence. Naked mole rats are the longest-living rodents, whose nervous system likely undergoes life-long adaptive reorganization. Nevertheless, neither the cellular organization of their cerebral cortex nor indices of structural neuronal plasticity along extreme time-scales have been established. We find that adult neurogenesis and neuronal migration are not unusual in naked mole rat brains. Instead, we show the prolonged expression of structural plasticity markers, many recognized as being developmentally controlled, and multi-year-long postnatal neuromorphogenesis and spatial synapse refinement in hippocampal and olfactory structures of the naked mole rat brain. Neurophysiological studies on identified hippocampal neurons demonstrated that morphological differentiation is disconnected from the control of excitability in all neuronal contingents regardless of their ability to self-renew. Overall, we conclude that naked mole rats show an extremely protracted period of brain maturation that may permit plasticity and resilience to neurodegenerative processes over their decades-long life span. This conclusion is consistent with the hypothesis that naked mole rats are neotenous, with retention of juvenile characteristics to permit survival in a hypoxic environment, with extreme longevity a consequence of greatly retarded development.
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry &Biophysics, Scheeles väg 1:A1, Karolinska Institutet, SE-17177 Stockholm, Sweden.
authors.forename: Orsolya K
authors.initials: OK
authors.lastname: Penz
authors.affiliation: 1] Division of Molecular Neurobiology, Department of Medical Biochemistry &Biophysics, Scheeles väg 1:A1, Karolinska Institutet, SE-17177 Stockholm, Sweden [2] Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria.
authors.forename: Janos
authors.initials: J
authors.lastname: Fuzik
authors.affiliation: Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria.
authors.forename: Aleksandra B
authors.initials: AB
authors.lastname: Kurek
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry &Biophysics, Scheeles väg 1:A1, Karolinska Institutet, SE-17177 Stockholm, Sweden.
authors.forename: Roman
authors.initials: R
authors.lastname: Romanov
authors.affiliation: 1] Department of Biological Sciences, University of Illinois, 840 West Taylor Street, Chicago, IL 60607, USA [2] Laboratory for Integrative Neuroscience, University of Illinois, 840 West Taylor Street, Chicago, IL 60607, USA [3] Department of Psychiatry, University of Illinois College of Medicine, 1601 West Taylor Street, Chicago, IL 60612.
authors.forename: John
authors.initials: J
authors.lastname: Larson
authors.affiliation: 1] Department of Biological Sciences, University of Illinois, 840 West Taylor Street, Chicago, IL 60607, USA [2] Laboratory for Integrative Neuroscience, University of Illinois, 840 West Taylor Street, Chicago, IL 60607, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Park
authors.affiliation: 1] Division of Molecular Neurobiology, Department of Medical Biochemistry &Biophysics, Scheeles väg 1:A1, Karolinska Institutet, SE-17177 Stockholm, Sweden [2] Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria.
authors.forename: Tibor
authors.initials: T
authors.lastname: Harkany
authors.affiliation: 1] Division of Molecular Neurobiology, Department of Medical Biochemistry &Biophysics, Scheeles väg 1:A1, Karolinska Institutet, SE-17177 Stockholm, Sweden [2] Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria.
authors.forename: Erik
authors.initials: E
authors.lastname: Keimpema
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D055592:Biophysical Phenomena; D001921:Brain / Q000254:growth & development*; D056547:CA1 Region, Hippocampal / Q000502:physiology; D049109:Cell Proliferation; D003712:Dendrites / Q000502:physiology; D018891:Dentate Gyrus / Q000502:physiology; D008136:Longevity / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D019577:Mole Rats; D009024:Morphogenesis; D055495:Neurogenesis; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology; D066195:Piriform Cortex / Q000502:physiology; D013569:Synapses / Q000502:physiology