title: Age-related changes in behavior in C57BL/6J mice from young adulthood to middle age.
abstract: BACKGROUND
  Aging is considered to be associated with progressive changes in the brain and its associated sensory, motor, and cognitive functions. A large number of studies comparing young and aged animals have reported differences in various behaviors between age-cohorts, indicating behavioral dysfunctions related to aging. However, relatively little is known about behavioral changes from young adulthood to middle age, and the effect of age on behavior during the early stages of life remains to be understood. In order to investigate age-related changes in the behaviors of mice from young adulthood to middle age, we performed a large-scale analysis of the behavioral data obtained from our behavioral test battery involving 1739 C57BL/6J wild-type mice at 2-12 months of age.
  
  
  RESULTS
  Significant behavioral differences between age groups (2-3-, 4-5-, 6-7-, and 8-12-month-old groups) were found in all the behavioral tests, including the light/dark transition, open field, elevated plus maze, rotarod, social interaction, prepulse inhibition, Porsolt forced swim, tail suspension, Barnes maze, and fear conditioning tests, except for the hot plate test. Compared with the 2-3-month-old group, the 4-5- and 6-7-month-old groups exhibited decreased locomotor activity to novel environments, motor function, acoustic startle response, social behavior, and depression-related behavior, increased prepulse inhibition, and deficits in spatial and cued fear memory. For most behaviors, the 8-12-month-old group showed similar but more pronounced changes in most of these behaviors compared with the younger age groups. Older groups exhibited increased anxiety-like behavior in the light/dark transition test whereas those groups showed seemingly decreased anxiety-like behavior measured by the elevated plus maze test.
  
  
  CONCLUSIONS
  The large-scale analysis of behavioral data from our battery of behavioral tests indicated age-related changes in a wide range of behaviors from young adulthood to middle age in C57BL/6J mice, though these results might have been influenced by possible confounding factors such as the time of day at testing and prior test experience. Our results also indicate that relatively narrow age differences can produce significant behavioral differences during adulthood in mice. These findings provide an insight into our understanding of the neurobiological processes underlying brain function and behavior that are subject to age-related changes in early to middle life. The findings also indicate that age is one of the critical factors to be carefully considered when designing behavioral tests and interpreting behavioral differences that might be induced by experimental manipulations.
authors.affiliation: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan. hshoji@fujita-hu.ac.jp.|Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan. hshoji@fujita-hu.ac.jp.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Shoji
authors.affiliation: Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan. keizo@nips.go.jp.|Section of Behavior Patterns, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi, 444-8787, Japan. keizo@nips.go.jp.
authors.forename: Keizo
authors.initials: K
authors.lastname: Takao
authors.affiliation: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan. hattoris@fujita-hu.ac.jp.|Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan. hattoris@fujita-hu.ac.jp.
authors.forename: Satoko
authors.initials: S
authors.lastname: Hattori
authors.affiliation: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan. miyakawa@fujita-hu.ac.jp.|Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan. miyakawa@fujita-hu.ac.jp.|Section of Behavior Patterns, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi, 444-8787, Japan. miyakawa@fujita-hu.ac.jp.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyakawa
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001522:Behavior, Animal; D001835:Body Weight; D005239:Fear; D007103:Immobilization; D008568:Memory; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D053580:Muscle Strength; D010146:Pain / Q000503:physiopathology; D065808:Prepulse Inhibition; D013216:Reflex, Startle; D012919:Social Behavior; D065853:Spatial Learning
references.citation: Physiol Behav. 1996 Nov;60(5):1247-54
references.pmid: 8916178
references.citation: Eur J Neurosci. 2006 Feb;23(3):711-28
references.pmid: 16487153
references.citation: Behav Brain Res. 2008 Dec 16;195(1):147-52
references.pmid: 18585406
references.citation: Front Aging Neurosci. 2012 Sep 12;4:12
references.pmid: 22988436
references.citation: J Neurosci. 2005 Sep 21;25(38):8680-5
references.pmid: 16177036
references.citation: Psychopharmacology (Berl). 2000 Feb;148(2):164-70
references.pmid: 10663431
references.citation: Behav Brain Res. 2004 May 5;151(1-2):1-8
references.pmid: 15084415
references.citation: Neuroscience. 2000;95(1):293-307
references.pmid: 10619486
references.citation: Neurobiol Aging. 1999 Jan-Feb;20(1):9-18
references.pmid: 10466889
references.citation: Physiol Behav. 2001 Aug;73(5):705-17
references.pmid: 11566205
references.citation: Lancet Neurol. 2011 Dec;10(12):1108-18
references.pmid: 22094131
references.citation: Behav Brain Res. 2000 Sep;114(1-2):153-65
references.pmid: 10996056
references.citation: Exp Gerontol. 1984;19(1):25-9
references.pmid: 6723816
references.citation: Nature. 2001 May 17;411(6835):309-13
references.pmid: 11357133
references.citation: Behav Brain Res. 1993 Nov 30;57(2):163-73
references.pmid: 8117421
references.citation: Exp Gerontol. 1999 Sep;34(6):797-808
references.pmid: 10579639
references.citation: Physiol Behav. 2000 Dec;71(5):509-16
references.pmid: 11239669
references.citation: Physiol Behav. 2011 Jan 10;102(1):115-20
references.pmid: 20888354
references.citation: Age (Dordr). 2012 Dec;34(6):1435-52
references.pmid: 21989972
references.citation: Mamm Genome. 1997 Oct;8(10):711-3
references.pmid: 9321461
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1624-9
references.pmid: 20080589
references.citation: Mol Brain. 2014;7:31
references.pmid: 24758191
references.citation: Neurobiol Aging. 2001 Mar-Apr;22(2):323-32
references.pmid: 11182482
references.citation: Neurobiol Aging. 2007 Oct;28(10):1577-93
references.pmid: 17010477
references.citation: Nat Rev Neurosci. 2006 Jan;7(1):30-40
references.pmid: 16371948
references.citation: Behav Brain Res. 2000 Mar;108(2):197-203
references.pmid: 10701663
references.citation: Front Aging Neurosci. 2011 May 25;3:9
references.pmid: 21647305
references.citation: Behav Neurosci. 1994 Aug;108(4):703-13
references.pmid: 7986364
references.citation: Physiol Behav. 1994 Feb;55(2):341-5
references.pmid: 8153176
references.citation: Learn Mem. 2008 Oct;15(10):733-46
references.pmid: 18832560
references.citation: Behav Brain Res. 2009 Mar 2;198(1):247-51
references.pmid: 18996418
references.citation: Neuropsychopharmacology. 2002 Dec;27(6):914-23
references.pmid: 12464448
references.citation: Physiol Behav. 1996 Aug;60(2):541-7
references.pmid: 8840916
references.citation: Behav Brain Res. 2007 Dec 11;185(1):43-8
references.pmid: 17707521
references.citation: Behav Brain Res. 2005 Dec 7;165(2):160-71
references.pmid: 16154210
references.citation: Nat Protoc. 2007;2(2):322-8
references.pmid: 17406592
references.citation: J Vis Exp. 2008;(22). pii: 1088. doi: 10.3791/1088
references.pmid: 19229173
references.citation: Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11686-91
references.pmid: 21709248
references.citation: Exp Gerontol. 2007 Jan-Feb;42(1-2):37-45
references.pmid: 16809014
references.citation: J Vis Exp. 2014;(85). doi: 10.3791/50871
references.pmid: 24637495
references.citation: Exp Toxicol Pathol. 2003 Jul;55(1):69-83
references.pmid: 12940631
references.citation: Horm Behav. 1997 Jun;31(3):197-211
references.pmid: 9213134
references.citation: Mol Brain. 2013;6:12
references.pmid: 23497716
references.citation: Psychopharmacology (Berl). 1985;85(3):367-70
references.pmid: 3923523
references.citation: Behav Brain Res. 2001 Nov 1;125(1-2):141-9
references.pmid: 11682105
references.citation: Neurobiol Learn Mem. 2007 Mar;87(3):309-23
references.pmid: 17079170
references.citation: Gerontologia. 1974;20(3):155-62
references.pmid: 4461327
references.citation: Endocrinology. 2005 Jul;146(7):3105-12
references.pmid: 15831572
references.citation: Pharmacol Biochem Behav. 1980 Aug;13(2):167-70
references.pmid: 6106204
references.citation: Physiol Behav. 2011 Jan 10;102(1):58-62
references.pmid: 20937292
references.citation: Eur J Pharmacol. 2003 Feb 28;463(1-3):163-75
references.pmid: 12600708
references.citation: Neuroscience. 2011 Jan 13;172:256-69
references.pmid: 21036203
references.citation: Nature. 2010 Mar 25;464(7288):529-35
references.pmid: 20336135
references.citation: Psychopharmacology (Berl). 1979 Aug 8;64(2):127-9
references.pmid: 40287
references.citation: Eur J Pharmacol. 1990 Mar 13;178(1):135-8
references.pmid: 1970538
references.citation: Neuroscience. 2006;137(2):413-23
references.pmid: 16330151
references.citation: Genes Brain Behav. 2004 Feb;3(1):27-38
references.pmid: 14960013
references.citation: Front Behav Neurosci. 2010 Sep 30;4:null
references.pmid: 20953248
references.citation: Pharmacol Biochem Behav. 1998 Apr;59(4):807-11
references.pmid: 9586835
references.citation: Eur J Pharmacol. 2003 Feb 28;463(1-3):55-65
references.pmid: 12600702
references.citation: Genes Brain Behav. 2003 Aug;2(4):214-9
references.pmid: 12953787
references.citation: Mol Brain. 2014;7:21
references.pmid: 24678719
references.citation: Mol Brain. 2014;7:44
references.pmid: 24893573
references.citation: Biol Psychiatry. 2006 Jun 15;59(12):1198-207
references.pmid: 16797265
references.citation: Neurosci Lett. 2006 Jun 19;401(1-2):183-7
references.pmid: 16581184
references.citation: Science. 2010 May 7;328(5979):753-6
references.pmid: 20448184
references.citation: Front Behav Neurosci. 2010 Jun 14;4:29
references.pmid: 20676234
references.citation: J Neurosci. 2008 Oct 1;28(40):9910-9
references.pmid: 18829949
references.citation: Science. 1999 Jun 4;284(5420):1670-2
references.pmid: 10356397
references.citation: J Neurosci. 2001 Jul 15;21(14):5239-50
references.pmid: 11438599
references.citation: Neuropsychopharmacology. 2013 Jul;38(8):1409-25
references.pmid: 23389689
references.citation: Neuron. 2008 Mar 27;57(6):809-18
references.pmid: 18367082
references.citation: Proc Natl Acad Sci U S A. 1996 May 14;93(10):4765-9
references.pmid: 8643477
references.citation: Physiol Behav. 1996 Nov;60(5):1191-7
references.pmid: 8916170
references.citation: Arch Int Pharmacodyn Ther. 1977 Oct;229(2):327-36
references.pmid: 596982
references.citation: Eur J Pharmacol. 2003 Feb 28;463(1-3):35-53
references.pmid: 12600701
references.citation: Prog Neurobiol. 2003 Feb;69(3):143-79
references.pmid: 12758108
references.citation: J Bone Miner Res. 2002 Jun;17(6):1044-50
references.pmid: 12054159
references.citation: Psychopharmacology (Berl). 2001 Feb;153(4):443-9
references.pmid: 11243491
references.citation: Neurosci Res. 2007 Jun;58(2):124-32
references.pmid: 17524507
references.citation: J Gerontol. 1990 May;45(3):B101-4
references.pmid: 2335717
references.citation: J Gerontol. 1986 Jan;41(1):8-12
references.pmid: 3941261
references.citation: Genes Brain Behav. 2008 Jun;7(4):496-505
references.pmid: 18182070
references.citation: J Comp Physiol Psychol. 1979 Feb;93(1):74-104
references.pmid: 221551
references.citation: Behav Brain Res. 2006 Sep 25;172(2):307-15
references.pmid: 16814879
references.citation: Exp Gerontol. 2012 Aug;47(8):552-64
references.pmid: 22583982
references.citation: Learn Mem. 1999 Mar-Apr;6(2):111-9
references.pmid: 10327236
references.citation: Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5280-5
references.pmid: 10220457
references.citation: Neurobiol Aging. 1981 Fall;2(3):199-203
references.pmid: 6171740
references.citation: Anesth Analg. 2004 May;98(5):1305-11, table of contents
references.pmid: 15105206
references.citation: Physiol Rev. 2002 Jul;82(3):637-72
references.pmid: 12087131
references.citation: Hear Res. 2004 Feb;188(1-2):21-8
references.pmid: 14759567
references.citation: J Vis Exp. 2006 Dec;(1):104
references.pmid: 18704188
references.citation: Eur J Pharmacol. 2003 Feb 28;463(1-3):3-33
references.pmid: 12600700
references.citation: Behav Brain Res. 2001 Aug 1;122(2):159-67
references.pmid: 11334646
references.citation: Front Behav Neurosci. 2012 Oct 02;6:58
references.pmid: 23060763
references.citation: Learn Mem. 2009 Jun;16(6):362-6
references.pmid: 19470651
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8987-92
references.pmid: 12851457
references.citation: Behav Neurosci. 2003 Jun;117(3):485-95
references.pmid: 12802877
references.citation: Neurobiol Aging. 1993 Jul-Aug;14(4):309-17
references.pmid: 8367012
references.citation: Physiol Behav. 1994 Sep;56(3):623-8
references.pmid: 7972418
references.citation: Exp Aging Res. 1976 May;2(3):221-33
references.pmid: 190016
references.citation: Behav Brain Res. 2012 Apr 1;229(1):21-8
references.pmid: 22227508
references.citation: Brain Res Bull. 2012 May 1;88(1):3-12
references.pmid: 22142973
references.citation: Mol Brain. 2013;6:35
references.pmid: 23938054
references.citation: J Neurobiol. 2003 Jan;54(1):283-311
references.pmid: 12486710
references.citation: Neuropsychopharmacology. 2008 Sep;33(10):2341-51
references.pmid: 18075491
references.citation: Arch Gerontol Geriatr. 2009 Jul-Aug;49(1):39-42
references.pmid: 18524397
references.citation: Behav Brain Res. 2008 Jan 10;186(1):32-40
references.pmid: 17716752
references.citation: Behav Brain Res. 2007 Feb 12;177(1):80-9
references.pmid: 17126421
references.citation: J Neurosci Methods. 1980 Jun;2(3):219-38
references.pmid: 6120260
references.citation: Neurobiol Aging. 1981 Fall;2(3):221-7
references.pmid: 7312100
references.citation: Brain Res Rev. 2007 Aug;55(1):78-88
references.pmid: 17561265