Impact of age and caloric restriction on neurogenesis in the dentate gyrus of C57BL/6 mice

Bondolfi, Luca; Ermini, Florian; Long, Jefferey M; Ingram, Donald K; Jucker, Mathias

doi:10.1016/S0197-4580(03)00083-6

« Previous Next »Neurobiology of Aging
Volume 25, Issue 3 , Pages 333-340, March 2004

Impact of age and caloric restriction on neurogenesis in the dentate gyrus of C57BL/6 mice

Luca Bondolfi
- Department of Neuropathology, Institute of Pathology, University of Basel, Schönbeinstrasse 40, CH-4003 Basel, Switzerland
- Contributed equally.
Florian Ermini
- Department of Neuropathology, Institute of Pathology, University of Basel, Schönbeinstrasse 40, CH-4003 Basel, Switzerland
- Contributed equally.
Jefferey M Long
- Laboratory of Experimental Gerontology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
- Present address: Medical Teaching Facility, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Donald K Ingram
- Laboratory of Experimental Gerontology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
Mathias Jucker
- Department of Neuropathology, Institute of Pathology, University of Basel, Schönbeinstrasse 40, CH-4003 Basel, Switzerland
- Department of Cellular Neurology, Hertie-Institute of Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany
- Corresponding author. Tel.: +41-61-265-2894; fax: +41-61-265-3194.

Received 2 January 2003; received in revised form 10 April 2003; accepted 11 April 2003.

Abstract

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.

Keywords: Mouse brain, Aging, Neurogenesis, Glia, Caloric restriction, Hippocampus, Progenitor cells, Proliferation, Gliogenesis