Increased neurogenesis in dentate gyrus of long-lived Ames dwarf mice.
Neurogenesis occurs throughout adult life in the dentate gyrus of mammalian hippocampus and has been suggested to play an important role in cognitive function. Multiple trophic factors including IGF-I have been demonstrated to regulate hippocampal neurogenesis. Ames dwarf mice live considerably longer than normal animals and maintain physiological function at youthful levels, including cognitive function, despite a deficiency of circulating GH and IGF-I. Here we show an increase in numbers of newly generated cells [bromodeoxyuridine (BrdU) positive] and newborn neurons (neuronal nuclear antigen and BrdU positive) in the dentate gyrus of adult dwarf mice compared with normal mice using BrdU labeling. Despite the profound suppression of hippocampal GH expression, hippocampal IGF-I protein levels are up-regulated and the corresponding mRNAs are as high in Ames dwarf as in normal mice. Our results suggest that local/hippocampal IGF-I expression may have induced the increase in hippocampal neurogenesis, and increased neurogenesis might contribute to the maintenance of youthful levels of cognitive function during aging in these long-lived animals.
Sun
Liou Y
LY
Geriatrics Research, Department of Internal Medicine, Southern Illinois University School of Medicine, Room 4389, 801 North Rutledge, Springfield, Illinois 62794-9628, USA.
Evans
M Steven
MS
Hsieh
Jenny
J
Panici
Jacob
J
Bartke
Andrzej
A
D000375:Aging; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000494:pharmacology; D049109:Cell Proliferation; D003071:Cognition; D004396:Coloring Agents / Q000494:pharmacology; D017931:DNA Primers / Q000737:chemistry; D018891:Dentate Gyrus / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D004392:Dwarfism / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D013006:Growth Hormone / Q000172:deficiency / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000502:physiology*; D008136:Longevity; D051379:Mice; D008817:Mice, Mutant Strains; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology; D015854:Up-Regulation
D000963:Antimetabolites; D004396:Coloring Agents; D017931:DNA Primers; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D001973:Bromodeoxyuridine