Impact of age and caloric restriction on neurogenesis in the dentate gyrus of C57BL/6 mice.
Age-related changes in neurogenesis and its modulation by caloric restriction (CR) were studied in C57BL/6 mice. To this end, bromodeoxyuridine (BrdU) labeling was used to assess neuronal and glial precursor proliferation and survival in the granular cell layer (GCL) and the hilus of the dentate gyrus of 2-, 12-, 18-, and 24-month-old mice. For both regions, we found an age-dependent decrease in proliferation but not in survival of newborn cells. Interestingly, the reduction in proliferation occurred between 2 and 18 months of age with no additional decline between 18- and 24-month-old mice. Phenotyping of the newborn cells revealed a decrease in the neuron fraction in the GCL between 2 and 12 months of age but not thereafter. The majority of BrdU cells in the hilus colocalized with astrocytic but none with neuronal markers. CR from 3 to 11 months of age had no effect on neurogenesis in the GCL, but had a survival-promoting effect on newly generated glial cells in the hilus of the dentate gyrus. In conclusion, C57BL/6 mice reveal a substantial reduction in neurogenesis in the dentate gyrus until late adulthood with no further decline with aging. Long-term CR does not counteract this age-related decline in neurogenesis but promotes survival of hilar glial cells.
Bondolfi
Luca
L
Department of Neuropathology, Institute of Pathology, University of Basel, Schönbeinstrasse 40, CH-4003 Basel, Switzerland.
Ermini
Florian
F
Long
Jefferey M
JM
Ingram
Donald K
DK
Jucker
Mathias
M
D000375:Aging / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology; D015415:Biomarkers; D001973:Bromodeoxyuridine; D031204:Caloric Restriction; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D018891:Dentate Gyrus / Q000166:cytology / Q000254:growth & development* / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D005508:Food Deprivation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
D015415:Biomarkers; D009419:Nerve Tissue Proteins; D001973:Bromodeoxyuridine