title: Adult hippocampal neurogenesis and c-Fos induction during escalation of voluntary wheel running in C57BL/6J mice.
abstract: Voluntary wheel running activates dentate gyrus granule neurons and increases adult hippocampal neurogenesis. Average daily running distance typically increases over a period of 3 weeks in rodents. Whether neurogenesis and cell activation are greater at the peak of running as compared to the initial escalation period is not known. Therefore, adult C57BL/6J male mice received 5 days of BrdU injections, at the same age, to label dividing cells during the onset of wheel access or after 21 days during peak levels of running or in sedentary conditions. Mice were sampled either 24h or 25 days after the last BrdU injection to measure cell proliferation and survival, respectively. Immunohistochemistry was performed on brain sections to identify the numbers of proliferating BrdU-labeled cells, and new neurons (BrdU/NeuN co-labeled) in the dentate gyrus. Ki67 was used as an additional mitotic marker. The induction of c-Fos was used to identify neurons activated from running. Mice ran approximately half as far during the first 5 days as compared to after 21 days. Running increased Ki67 cells at the onset but after 21 days levels were similar to sedentary. Numbers of BrdU cells were similar in all groups 24h after the final injection. However, after 25 days, running approximately doubled the survival of new neurons born either at the onset or peak of running. These changes co-varied with c-Fos expression. We conclude that sustained running maintains a stable rate of neurogenesis above sedentary via activity-dependent increases in differentiation and survival, not proliferation, of progenitor cells in the C57BL/6J model.
authors.affiliation: Department of Psychology, The Beckman Institute, University of Illinois at Urbana-Champaign, 405 N. Mathews Ave., Urbana, IL 61801, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Clark
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Kohman
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Miller
authors.forename: Tushar K
authors.initials: TK
authors.lastname: Bhattacharya
authors.forename: Erik H
authors.initials: EH
authors.lastname: Haferkamp
authors.forename: Justin S
authors.initials: JS
authors.lastname: Rhodes
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D013997:Time Factors
chemical_list: D016760:Proto-Oncogene Proteins c-fos
references.citation: Hippocampus. 2009 Oct;19(10):907-12
references.pmid: 19235230
references.citation: Neurosci Lett. 1994 Feb 14;167(1-2):101-4
references.pmid: 7909928
references.citation: Neuron. 2005 Sep 15;47(6):803-15
references.pmid: 16157276
references.citation: Neuron. 2004 May 27;42(4):535-52
references.pmid: 15157417
references.citation: Neuroscience. 1993 Sep;56(2):337-44
references.pmid: 8247264
references.citation: Nat Rev Neurosci. 2002 Sep;3(9):715-27
references.pmid: 12209120
references.citation: Behav Brain Res. 2009 Dec 1;204(1):175-81
references.pmid: 19520122
references.citation: Hippocampus. 2010 Mar;20(3):364-76
references.pmid: 19452518
references.citation: Brain Behav Immun. 2010 Mar;24(3):486-92
references.pmid: 20025957
references.citation: Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5263-7
references.pmid: 10220454
references.citation: Hippocampus. 2006;16(1):11-9
references.pmid: 16270325
references.citation: Exp Brain Res. 2001 Mar;137(1):26-35
references.pmid: 11310169
references.citation: Am J Physiol Heart Circ Physiol. 2004 Aug;287(2):H914-20
references.pmid: 15277206
references.citation: Brain Res Dev Brain Res. 2004 Jul 19;151(1-2):159-68
references.pmid: 15246702
references.citation: Nat Neurosci. 1999 Mar;2(3):266-70
references.pmid: 10195220
references.citation: Neurobiol Aging. 2006 Oct;27(10):1505-13
references.pmid: 16271278
references.citation: Behav Neurosci. 2003 Oct;117(5):1006-16
references.pmid: 14570550
references.citation: Neuroscience. 2008 Sep 9;155(4):1048-58
references.pmid: 18664375
references.citation: Behav Neurosci. 2003 Dec;117(6):1243-56
references.pmid: 14674844
references.citation: Eur J Neurosci. 2003 May;17(10):2042-6
references.pmid: 12786970
references.citation: Hippocampus. 2009 Oct;19(10):928-36
references.pmid: 19212941
references.citation: J Physiol. 2008 Aug 15;586(16):3745-9
references.pmid: 18511482
references.citation: Brain Res. 1985 Dec 30;361(1-2):99-106
references.pmid: 4084813
references.citation: Neurosci Res. 2006 Sep;56(1):45-52
references.pmid: 16793155
references.citation: J Neurophysiol. 2005 Dec;94(6):4528-32
references.pmid: 16033936
references.citation: Development. 2003 Jan;130(2):391-9
references.pmid: 12466205
references.citation: Nature. 2006 Feb 2;439(7076):589-93
references.pmid: 16341203
references.citation: Hippocampus. 2009 Oct;19(10):898-906
references.pmid: 19156854
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):780-5
references.pmid: 16407118
references.citation: Hippocampus. 2009 Oct;19(10):937-50
references.pmid: 19132736
references.citation: Eur J Neurosci. 2000 Jul;12(7):2211-4
references.pmid: 10947799
references.citation: Eur Neuropsychopharmacol. 2010 Jan;20(1):1-17
references.pmid: 19748235
references.citation: Nat Med. 1998 Nov;4(11):1313-7
references.pmid: 9809557
references.citation: Nature. 2002 Feb 28;415(6875):1030-4
references.pmid: 11875571
references.citation: Life Sci. 2003 Feb 7;72(12):1421-36
references.pmid: 12527039
references.citation: Neuroscience. 1994 Aug;61(4):739-44
references.pmid: 7838373
references.citation: J Neurosci. 2009 Apr 1;29(13):4239-51
references.pmid: 19339618
references.citation: Neurochem Res. 1996 Nov;21(11):1425-35
references.pmid: 8947933
references.citation: Exp Brain Res. 2005 Nov;167(1):136-40
references.pmid: 16041511