Neuroanatomical Changes Associated with Cognitive Aging

  • Janice M. JuraskaEmail author
  • Nioka C. Lowry
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 10)


The literature on the neuroanatomical changes that occur during normal, non-demented aging is reviewed here with an emphasis on the improved accuracy of studies that use stereological techniques. Loss of neural tissue involved in cognition occurs during aging of humans as well as the other mammals that have been examined. There is considerable regional specificity within the cerebral cortex and the hippocampus in both the degree and cellular basis for loss. The anatomy of the prefrontal cortex is especially vulnerable to the effects of aging while the major subfields of the hippocampus are not. A loss of neurons, dendrites and synapses has been documented, as well as changes in neurotransmitter systems, in some regions of the cortex and hippocampus but not others. Species differences are also apparent in the cortical white matter and the corpus callosum where there are indications of loss of myelin in humans, but most evidence favors preservation in rats. The examination of whether the course of neuroanatomical aging is altered by hormone replacement in females is just beginning. When hormone replacement is started close to the time of cycle cessation, there are indications in humans and rats that replacement can preserve neural tissue but there is some variability due to the type of hormones and regimen of administration.


Stereology Neuron number Dendrites Synapses Synaptophysin Dopamine Estrogen Progesterone Medroxyprogesterone acetate Hormone treatment Menopause Hippocampus Prefrontal cortex Acetylcholine Glutamate White matter Myelination Basolateral amygdala Corpus callosum 



Magnetic resonance imaging


Positron emission tomography


Single-photon emission computed tomography


Dopamine transporter


Monoamine oxidase A


Monoamine oxidase B


Messenger ribonucleic acid


Medial prefrontal cortex


N-methyl-d-aspartate receptor


Medroxyprogesterone acetate


17-β estradiol




Conjugated equine estrogens


Choline acetyltransferase





Our work was supported by grants from the National Institute of Aging, AG18046 and AG022499. We thank Wendy Koss and Renee Sadowski for comments on the manuscript.


  1. Adams MM, Shah RA, Janssen WG, Morrison JH (2001) Different modes of hippocampal plasticity in response to estrogenestrogen in young and aged female rats. Proc Natl Acad Sci U S A 98:8071–8076. doi: 10.1073/pnas.141215898 PubMedCrossRefGoogle Scholar
  2. Allard P, Marcusson JO (1989) Age-correlated loss of dopamine uptake sites labeled with [3H]GBR-12935 in human putamen. Neurobiol Aging 10:661–664PubMedCrossRefGoogle Scholar
  3. Allen JS, Bruss J, Brown CK, Damasio H (2005) Normal neuroanatomical variation due to age: the major lobes and a parcellation of the temporal region. Neurobiol Aging 26:1245–1260; discussion 1279–1282. doi: 10.1016/j.neurobiolaging.2005.05.023 Google Scholar
  4. Amenta F, Bograni S, Cadel S, Ferrante F, Valsecchi B, Vega JA (1994) Microanatomical changes in the frontal cortex of aged rats: effect of L-deprenyl treatment. Brain Res Bull 34:125–131PubMedCrossRefGoogle Scholar
  5. Antonini A, Leenders KL, Reist H, Thomann R, Beer HF, Locher J (1993) Effect of age on D2 dopamine receptors in normal human brain measured by positron emission tomography and 11C-raclopride. Arch Neurol 50:474–480PubMedCrossRefGoogle Scholar
  6. Azcoitia I, Perez-Martin M, Salazar V, Castillo C, Ariznavarreta C, Garcia-Segura LM, Tresguerres JA (2005) Growth hormone prevents neuronal loss in the aged rat hippocampus. Neurobiol Aging 26:697–703. doi: 10.1016/j.neurobiolaging.2004.06.007 PubMedCrossRefGoogle Scholar
  7. Bäckman L, Lindenberger U, Li SC, Nyberg L (2010) Linking cognitive aging to alterations in dopamine neurotransmitter functioning: recent data and future avenues. Neurosci Biobehav Rev 34:670–677. doi: 10.1016/j.neubiorev.2009.12.008 PubMedCrossRefGoogle Scholar
  8. Bannon MJ, Whitty CJ (1997) Age-related and regional differences in dopamine transporter mRNA expression in human midbrain. Neurology 48:969–977PubMedCrossRefGoogle Scholar
  9. Bartzokis G, Beckson M, Lu PH, Nuechterlein KH, Edwards N, Mintz J (2001) Age-related changes in frontal and temporal lobe volumes in men: a magnetic resonance imaging study. Arch Gen Psychiatry 58:461–465.PubMedCrossRefGoogle Scholar
  10. Baxter MG, Chiba AA (1999) Cognitive functions of the basal forebrain. Curr Opin Neurobiol 9:178–183PubMedCrossRefGoogle Scholar
  11. Black JE, Isaacs KR, Greenough WT (1991) Usual vs successful aging: some notes on experiential factors. Neurobiol Aging 12:325–328; discussion 352–355PubMedCrossRefGoogle Scholar
  12. Boccardi M, Ghidoni R, Govoni S, Testa C, Benussi L, Bonetti M, Binetti G, Frisoni GB (2006) Effects of hormone therapy on brain morphology of healthy postmenopausal women: a Voxel-based morphometry study. Menopause 13:584–591. doi: 10.1097/01.gme.0000196811.88505.10 PubMedCrossRefGoogle Scholar
  13. Bohacek J, Bearl AM, Daniel JM (2008) Long-term ovarian hormone deprivation alters the ability of subsequent oestradiol replacement to regulate choline acetyltransferase protein levels in the hippocampus and prefrontal cortex of middle-aged rats. J Neuroendocrinol 20:1023–1027. doi: 10.1111/j.1365-2826.2008.01752.x PubMedCrossRefGoogle Scholar
  14. Bowley MP, Cabral H, Rosene DL, Peters A (2010) Age changes in myelinated nerve fibers of the cingulate bundle and corpus callosum in the rhesus monkey. J Comp Neurol 518:3046–3064. doi: 10.1002/cne.22379 PubMedCrossRefGoogle Scholar
  15. Braden BB, Talboom JS, Crain ID, Simard AR, Lukas RJ, Prokai L, Scheldrup MR, Bowman BL, Bimonte-Nelson HA (2010) Medroxyprogesterone acetate impairs memory and alters the GABAergic system in aged surgically menopausal rats. Neurobiol Learn Mem 93:444–453. doi: 10.1016/j.nlm.2010.01.002 PubMedCrossRefGoogle Scholar
  16. Brody H (1955) Organization of the cerebral cortex. III. A study of aging in the human cerebral cortex. J Comp Neurol 102:511–516PubMedCrossRefGoogle Scholar
  17. Calhoun ME, Kurth D, Phinney AL, Long JM, Hengemihle J, Mouton PR, Ingram DK, Jucker M (1998) Hippocampal neuron and synaptophysin-positive bouton number in aging C57BL/6 mice. Neurobiol Aging 19:599–606PubMedCrossRefGoogle Scholar
  18. Castorina M, Ambrosini AM, Pacific L, Ramacci MT, Angelucci L (1994) Age-dependent loss of NMDA receptors in hippocampus, striatum, and frontal cortex of the rat: prevention by acetyl-L-carnitine. Neurochem Res 19:795–798PubMedCrossRefGoogle Scholar
  19. Casu MA, Wong TP, De Koninck Y, Ribeiro-da-Silva A, Cuello AC (2002) Aging causes a preferential loss of cholinergic innervation of characterized neocortical pyramidal neurons. Cereb Cortex 12:329–337PubMedCrossRefGoogle Scholar
  20. Chang YM, Rosene DL, Killiany RJ, Mangiamele LA, Luebke JI (2005) Increased action potential firing rates of layer 2/3 pyramidal cells in the prefrontal cortex are significantly related to cognitive performance in aged monkeys. Cereb Cortex 15:409–418. doi: 10.1093/cercor/bhh144 PubMedCrossRefGoogle Scholar
  21. Clemens JA, Meites J (1971) Neuroendocrine status of old constant-estrous rats. Neuroendocrinology 7:249–256PubMedCrossRefGoogle Scholar
  22. Cupp CJ, Uemura E (1980) Age-related changes in prefrontal cortex of Macaca mulatta: quantitative analysis of dendritic branching patterns. Exp Neurol 69:143–163. doi: 10.1016/0197-4580(91)90077 PubMedCrossRefGoogle Scholar
  23. Curcio CA, Coleman PD (1982) Stability of neuron number in cortical barrels of aging mice. J Comp Neurol 212:158–172. doi: 10.1002/cne.902120206 PubMedCrossRefGoogle Scholar
  24. Dawson R Jr, Wallace DR, Meldrum MJ (1989) Endogenous glutamate release from frontal cortex of adult and aged rats. Neurobiol Aging 10:665–668PubMedCrossRefGoogle Scholar
  25. de Brabander JM, Kramers RJ, Uylings HB (1998) Layer-specific dendritic regression of pyramidal cells with ageing in the human prefrontal cortex. Eur J Neurosci 10:1261–1269PubMedCrossRefGoogle Scholar
  26. de Keyser J, De Backer JP, Vauquelin G, Ebinger G (1990) The effect of aging on the D1 dopamine receptors in human frontal cortex. Brain Res 528:308–310PubMedCrossRefGoogle Scholar
  27. Duan H, Wearne SL, Rocher AB, Macedo A, Morrison JH, Hof PR (2003) Age-related dendritic and spine changes in corticocortically projecting neurons in macaque monkeys. Cereb Cortex 13:950–961PubMedCrossRefGoogle Scholar
  28. Dumitriu D, Hao J, Hara Y, Kaufmann J, Janssen WG, Lou W, Rapp PR, Morrison JH (2010) Selective changes in thin spine density and morphology in monkey prefrontal cortex correlate with aging-related cognitive impairment. J Neurosci 30:7507–7515. doi: 10.1523/JNEUROSCI.6410-09.2010 PubMedCrossRefGoogle Scholar
  29. Eastwood SL, Weickert CS, Webster MJ, Herman MM, Kleinman JE, Harrison PJ (2006) Synaptophysin protein and mRNA expression in the human hippocampal formation from birth to old age. Hippocampus 16:645–654. doi: 10.1002/hipo.20194 PubMedCrossRefGoogle Scholar
  30. Espeland MA, Rapp SR, Shumaker SA, Brunner R, Manson JE, Sherwin BB, Hsia J, Margolis KL, Hogan PE, Wallace R, Dailey M, Freeman R, Hays J, Women’s Health Initiative Memory Study (2004) Conjugated equine estrogens and global cognitive function in postmenopausal women: Women’s Health Initiative Memory Study. JAMA 291:2959–2968. doi: 10.1001/jama.291.24.2959 PubMedCrossRefGoogle Scholar
  31. Feldman ML, Dowd C (1975) Loss of dendritic spines in aging cerebral cortex. Anat Embryol (Berl) 148:279–301CrossRefGoogle Scholar
  32. Fernandez SM, Frick KM (2004) Chronic oral estrogen affects memory and neurochemistry in middle-aged female mice. Behav Neurosci 118:1340–1351. doi: 10.1037/0735-7044.118.6.1340 PubMedCrossRefGoogle Scholar
  33. Fischer W, Bjorklund A, Chen K, Gage FH (1991) NGF improves spatial memory in aged rodents as a function of age. J Neurosci 11:1889–1906PubMedGoogle Scholar
  34. Fjell AM, Walhovd KB, Fennema-Notestine C, McEvoy LK, Hagler DJ, Holland D, Brewer JB, Dale AM (2009) One-year brain atrophy evident in healthy aging. J Neurosci 29:15223–15231. doi: 10.1523/JNEUROSCI.3252-09.2009 PubMedCrossRefGoogle Scholar
  35. Frick KM, Fernandez SM, Bulinski SC (2002) Estrogen replacement improves spatial reference memory and increases hippocampal synaptophysin in aged female mice. Neuroscience 115:547–558PubMedCrossRefGoogle Scholar
  36. Fuchs E, Flugge G, Czeh B (2006) Remodeling of neuronal networks by stress. Front Biosci 11:2746–2758PubMedCrossRefGoogle Scholar
  37. Gallagher M, Rapp PR (1997) The use of animal models to study the effects of aging on cognition. Annu Rev Psychol 48:339–370. doi: 10.1146/annurev.psych.48.1.339 PubMedCrossRefGoogle Scholar
  38. Gazzaley AH, Siegel SJ, Kordower JH, Mufson EJ, Morrison JH (1996) Circuit-specific alterations of N-methyl-D-aspartate receptor subunit 1 in the dentate gyrus of aged monkeys. Proc Natl Acad Sci USA 93:3121–3125PubMedCrossRefGoogle Scholar
  39. Geinisman Y, Ganeshina O, Yoshida R, Berry RW, Disterhoft JF, Gallagher M (2004) Aging, spatial learning, and total synapse number in the rat CA1 stratum radiatum. Neurobiol Aging 25:407–416. doi: 10.1016/j.neurobiolaging.2003.12.001 PubMedCrossRefGoogle Scholar
  40. Gibbs RB (2010) Estrogen therapy and cognition: a review of the cholinergic hypothesis. Endocr Rev 31:224–253. doi: 10.1210/er.2009-0036 PubMedCrossRefGoogle Scholar
  41. Gibbs RB, Mauk R, Nelson D, Johnson DA (2009) Donepezil treatment restores the ability of estradiol to enhance cognitive performance in aged rats: evidence for the cholinergic basis of the critical period hypothesis. Horm Behav 56:73–83. doi: 10.1016/j.yhbeh.2009.03.003 PubMedCrossRefGoogle Scholar
  42. Gibbs RB, Edwards D, Lazar N, Nelson D, Talameh J (2006) Effects of long-term hormone treatment and of tibolone on monoamines and monoamine metabolites in the brains of ovariectomised, Cynomologous monkeys. J Neuroendocrinol 18:643–654. doi: 10.1111/j.1365-2826.2006.01463.x PubMedCrossRefGoogle Scholar
  43. Gibbs RB (2003) Effects of ageing and long-term hormone replacement on cholinergic neurones in the medial septum and nucleus basalis magnocellularis of ovariectomized rats. J Neuroendocrinol 15:477–485PubMedCrossRefGoogle Scholar
  44. Gibbs RB, Nelson D, Anthony MS, Clarkson TB (2002) Effects of long-term hormone replacement and of tibolone on choline acetyltransferase and acetylcholinesterase activities in the brains of ovariectomized, cynomologus monkeys. Neuroscience 113:907–914PubMedCrossRefGoogle Scholar
  45. Gibbs RB (2000) Long-term treatment with estrogen and progesteroneprogesterone enhances acquisition of a spatial memory task by ovariectomized aged rats. Neurobiol Aging 21:107–116. doi: 10.1016/S0197-4580(00)00103-2 PubMedCrossRefGoogle Scholar
  46. Gibson GE, Peterson C, Jenden DJ (1981) Brain acetylcholine synthesis declines with senescence. Science 213:674–676PubMedCrossRefGoogle Scholar
  47. Gibson PH (1983) EM study of the numbers of cortical synapses in the brains of ageing people and people with Alzheimer-type dementia. Acta Neuropathol 62:127–133PubMedCrossRefGoogle Scholar
  48. Goldman-Rakic PS, Brown RM (1981) Regional changes of monoamines in cerebral cortex and subcortical structures of aging rhesus monkeys. Neuroscience 6:177–187PubMedCrossRefGoogle Scholar
  49. Gozlan H, Daval G, Verge D, Spampinato U, Fattaccini CM, Gallissot MC, el Mestikawy S, Hamon M (1990) Aging associated changes in serotoninergic and dopaminergic pre- and postsynaptic neurochemical markers in the rat brain. Neurobiol Aging 11:437–449PubMedCrossRefGoogle Scholar
  50. Gratton G, Wee E, Rykhlevskaia EI, Leaver EE, Fabiani M (2009) Does white matter matter? Spatio-temporal dynamics of task switching in aging. J Cogn Neurosci 21:1380–1395. doi: 10.1162/jocn.2009.21093 PubMedCrossRefGoogle Scholar
  51. Green EJ, Greenough WT, Schlumpf BE (1983) Effects of complex or isolated environments on cortical dendrites of middle-aged rats. Brain Res 264:233–240PubMedCrossRefGoogle Scholar
  52. Greenough WT, McDonald JW, Parnisari RM, Camel JE (1986) Environmental conditions modulate degeneration and new dendrite growth in cerebellum of senescent rats. Brain Res 380:136–143PubMedCrossRefGoogle Scholar
  53. Grill JD, Riddle DR (2002) Age-related and laminar-specific dendritic changes in the medial frontal cortex of the rat. Brain Res 937:8–21PubMedCrossRefGoogle Scholar
  54. Gunning-Dixon FM, Brickman AM, Cheng JC, Alexopoulos GS (2009) Aging of cerebral white matter: a review of MRI findings. Int J Geriatr Psychiatry 24:109–117. doi: 10.1002/gps.2087 PubMedCrossRefGoogle Scholar
  55. Haley GE, Kohama SG, Urbanski HF, Raber J (2010) Age-related decreases in SYN levels associated with increases in MAP-2, apoE, and GFAP levels in the rhesus macaque prefrontal cortex and hippocampus Age (Dordr) 32:283–296. doi: 10.1007/s11357-010-9137-9 CrossRefGoogle Scholar
  56. Hao J, Rapp PR, Janssen WG, Lou W, Lasley BL, Hof PR, Morrison JH (2007) Interactive effects of age and estrogen on cognition and pyramidal neurons in monkey prefrontal cortex. Proc Natl Acad Sci USA 104:11465–11470. doi: 10.1073/pnas.0704757104 PubMedCrossRefGoogle Scholar
  57. Hao J, Rapp PR, Leffler AE, Leffler SR, Janssen WG, Lou W, McKay H, Roberts JA, Wearne SL, Hof PR, Morrison JH (2006) Estrogen alters spine number and morphology in prefrontal cortex of aged female rhesus monkeys. J Neurosci 26:2571–2578. doi: 10.1523/JNEUROSCI.3440-05.2006 PubMedCrossRefGoogle Scholar
  58. Harada N, Nishiyama S, Satoh K, Fukumoto D, Kakiuchi T, Tsukada H (2002) Age-related changes in the striatal dopaminergic system in the living brain: a multiparametric PET study in conscious monkeys. Synapse 45:38–45. doi: 10.1002/syn.10082 PubMedCrossRefGoogle Scholar
  59. Heumann D, Leuba G (1983) Neuronal death in the development and aging of the cerebral cortex of the mouse. Neuropathol Appl Neurobiol 9:297–311PubMedCrossRefGoogle Scholar
  60. Himi T, Cao M, Mori N (1995) Reduced expression of the molecular markers of dopaminergic neuronal atrophy in the aging rat brain. J Gerontol A Biol Sci Med Sci 50:B193–200PubMedCrossRefGoogle Scholar
  61. Hof PR, Duan H, Page TL, Einstein M, Wicinski B, He Y, Erwin JM, Morrison JH (2002) Age-related changes in GluR2 and NMDAR1 glutamate receptor subunit protein immunoreactivity in corticocortically projecting neurons in macaque and patas monkeys. Brain Res 928:175–186PubMedCrossRefGoogle Scholar
  62. Hof PR, Nimchinsky EA, Young WG, Morrison JH (2000) Numbers of meynert and layer IVB cells in area V1: a stereologic analysis in young and aged macaque monkeys. J Comp Neurol 420:113–126PubMedCrossRefGoogle Scholar
  63. Holmes A, Wellman CL (2009) Stress-induced prefrontal reorganization and executive dysfunction in rodents. Neurosci Biobehav Rev 33:773–783. doi: 10.1016/j.neubiorev.2008.11.005 PubMedCrossRefGoogle Scholar
  64. Huttenlocher PR (1979) Synaptic density in human frontal cortex–developmental changes and effects of aging. Brain Res 163:195–205PubMedCrossRefGoogle Scholar
  65. Hyttel J (1987) Age related decrease in the density of dopamine D1 and D2 receptors in corpus striatum of rats. Pharmacol Toxicol 61:126–129PubMedCrossRefGoogle Scholar
  66. Ichise M, Ballinger JR, Tanaka F, Moscovitch M, St George-Hyslop PH, Raphael D, Freedman M (1998) Age-related changes in D2 receptor binding with iodine-123-iodobenzofuran SPECT. J Nucl Med 39:1511–1518PubMedGoogle Scholar
  67. Inoue M, Suhara T, Sudo Y, Okubo Y, Yasuno F, Kishimoto T, Yoshikawa K, Tanada S (2001) Age-related reduction of extrastriatal dopamine D2 receptor measured by PET. Life Sci 69:1079–1084PubMedCrossRefGoogle Scholar
  68. Jacobs B, Driscoll L, Schall M (1997) Life-span dendritic and spine changes in areas 10 and 18 of human cortex: a quantitative Golgi study. J Comp Neurol 386:661–680PubMedCrossRefGoogle Scholar
  69. Kaasinen V, Kemppainen N, Nagren K, Helenius H, Kurki T, Rinne JO (2002) Age-related loss of extrastriatal dopamine D(2) -like receptors in women. J Neurochem 81:1005–1010PubMedCrossRefGoogle Scholar
  70. Kaasinen V, Vilkman H, Hietala J, Nagren K, Helenius H, Olsson H, Farde L, Rinne J (2000) Age-related dopamine D2/D3 receptor loss in extrastriatal regions of the human brain. Neurobiol Aging 21:683–688PubMedCrossRefGoogle Scholar
  71. Kabaso D, Coskren PJ, Henry BI, Hof PR, Wearne SL (2009) The electrotonic structure of pyramidal neurons contributing to prefrontal cortical circuits in macaque monkeys is significantly altered in aging. Cereb Cortex 19:2248–2268. doi: 10.1093/cercor/bhn242 PubMedCrossRefGoogle Scholar
  72. Keuker JI, de Biurrun G, Luiten PG, Fuchs E (2004) Preservation of hippocampal neuron numbers and hippocampal subfield volumes in behaviorally characterized aged tree shrews. J Comp Neurol 468:509–517. doi: 10.1002/cne.10996 PubMedCrossRefGoogle Scholar
  73. Keuker JI, Luiten PG, Fuchs E (2003) Preservation of hippocampal neuron numbers in aged rhesus monkeys. Neurobiol Aging 24:157–165PubMedCrossRefGoogle Scholar
  74. Klempin F, Kempermann G (2007) Adult hippocampal neurogenesis and aging. Eur Arch Psychiatry Clin Neurosci 257:271–280. doi: 10.1007/s00406-007-0731-5 PubMedCrossRefGoogle Scholar
  75. Krettek JE, Price JL (1977) Projections from the amygdaloid complex to the cerebral cortex and thalamus in the rat and cat. J Comp Neurol 172:687–722. doi: 10.1002/cne.901720408 PubMedCrossRefGoogle Scholar
  76. Lai H, Bowden DM, Horita A (1987) Age-related decreases in dopamine receptors in the caudate nucleus and putamen of the rhesus monkey (Macaca mulatta). Neurobiol Aging 8:45–49PubMedCrossRefGoogle Scholar
  77. Lord C, Engert V, Lupien SJ, Pruessner JC (2010) Effect of sex and estrogen therapy on the aging brain: a voxel-based morphometry study. Menopause 17:846–851. doi: 10.1097/gme.0b013e3181e06b83 PubMedCrossRefGoogle Scholar
  78. Lowry NC, Yates MA, Juraska JM (2008) Ovarian hormones in aged female rats benefit acquisistion of a spatial alternation task, but do not improve performance during delayed alternation. Soc Neurosci Abs OnlineGoogle Scholar
  79. Lowry NC, Pardon LP, Yates MA, Juraska JM (2010) Effects of long-term treatment with 17 beta-estradiol and medroxyprogesterone acetate on water maze performance in middle aged female rats. Horm Behav 58:200–207. doi: 10.1016/j.yhbeh.2010.03.018 PubMedCrossRefGoogle Scholar
  80. Magnusson KR, Cotman CW (1993) Age-related changes in excitatory amino acid receptors in two mouse strains. Neurobiol Aging 14:197–206PubMedCrossRefGoogle Scholar
  81. Markham JA, Herting MM, Luszpak AE, Juraska JM, Greenough WT (2009) Myelination of the corpus callosum in male and female rats following complex environment housing during adulthood. Brain Res 1288:9–17. doi: 10.1016/j.brainres.2009.06.087 PubMedCrossRefGoogle Scholar
  82. Markham JA, McKian KP, Stroup TS, Juraska JM (2005) Sexually dimorphic aging of dendritic morphology in CA1 of hippocampus. Hippocampus 15:97–103. doi: 10.1002/hipo.20034 PubMedCrossRefGoogle Scholar
  83. Markham JA, Juraska JM (2002) Aging and sex influence the anatomy of the rat anterior cingulate cortex. Neurobiol Aging 23:579–588PubMedCrossRefGoogle Scholar
  84. Marner L, Nyengaard JR, Tang Y, Pakkenberg B (2003) Marked loss of myelinated nerve fibers in the human brain with age. J Comp Neurol 462:144–152. doi: 10.1002/cne.10714 PubMedCrossRefGoogle Scholar
  85. McCullough LD, Hurn PD (2003) Estrogen and ischemic neuroprotection: an integrated view. Trends Endocrinol Metab 14:228–235PubMedCrossRefGoogle Scholar
  86. McDermott JL (1993) Effects of estrogen upon dopamine release from the corpus striatum of young and aged female rats. Brain Res 606:118–125PubMedCrossRefGoogle Scholar
  87. McEntee WJ, Crook TH (1993) Glutamate: its role in learning, memory, and the aging brain. Psychopharmacology (Berl) 111:391–401CrossRefGoogle Scholar
  88. Meier-Ruge W, Ulrich J, Bruhlmann M, Meier E (1992) Age-related white matter atrophy in the human brain. Ann N Y Acad Sci 673:260–269PubMedCrossRefGoogle Scholar
  89. Mesco ER, Carlson SG, Joseph JA, Roth GS (1993) Decreased striatal D2 dopamine receptor mRNA synthesis during aging. Brain Res Mol Brain Res 17:160–162PubMedCrossRefGoogle Scholar
  90. Mesulam MM, Mufson EJ, Levey AI, Wainer BH (1983) Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. J Comp Neurol 214:170–197. doi: 10.1002/cne.902140206 PubMedCrossRefGoogle Scholar
  91. Miyoshi R, Kito S, Doudou N, Nomoto T (1990) Age-related changes of strychnine-insensitive glycine receptors in rat brain as studied by in vitro autoradiography. Synapse 6:338–343. doi: 10.1002/syn.890060405 PubMedCrossRefGoogle Scholar
  92. Mizoguchi K, Shoji H, Tanaka Y, Maruyama W, Tabira T (2009) Age-related spatial working memory impairment is caused by prefrontal cortical dopaminergic dysfunction in rats. Neuroscience 162:1192–1201. doi: 10.1016/j.neuroscience.2009.05.023 PubMedCrossRefGoogle Scholar
  93. Moore H, Stuckman S, Sarter M, Bruno JP (1996) Potassium, but not atropine-stimulated cortical acetylcholine efflux, is reduced in aged rats. Neurobiol Aging 17:565–571PubMedCrossRefGoogle Scholar
  94. Morris ED, Chefer SI, Lane MA, Muzic RF Jr, Wong DF, Dannals RF, Matochik JA, Bonab AA, Villemagne VL, Grant SJ, Ingram DK, Roth GS, London ED (1999) Loss of D2 receptor binding with age in rhesus monkeys: importance of correction for differences in striatal size. J Cereb Blood Flow Metab 19:218–229. doi: 10.1097/00004647-199902000-00013 PubMedCrossRefGoogle Scholar
  95. Neafsey EJ, Terreberry RR, Hurley KM, Ruit KG, Frysztak RJ (1993) Anterior cingulate cortex in rodents: connections, visceral control functions, and implications for emotion. In: Vogt BA, Gabriel M (eds) Neurobiology of cingulate cortex and limbic thalamus. Birkhauser, Boston, pp 206–223Google Scholar
  96. Nicolle MM, Gallagher M, McKinney M (1999) No loss of synaptic proteins in the hippocampus of aged, behaviorally impaired rats. Neurobiol Aging 20:343–348PubMedCrossRefGoogle Scholar
  97. O’Donnell KA, Rapp PR, Hof PR (1999) Preservation of prefrontal cortical volume in behaviorally characterized aged macaque monkeys. Exp Neurol 160:300–310. doi: 10.1006/exnr.1999.7192 PubMedCrossRefGoogle Scholar
  98. O’Steen WK, Spencer RL, Bare DJ, McEwen BS (1995) Analysis of severe photoreceptor loss and Morris water-maze performance in aged rats. Behav Brain Res 68:151–158PubMedCrossRefGoogle Scholar
  99. O’Sullivan M, Jones DK, Summers PE, Morris RG, Williams SC, Markus HS (2001) Evidence for cortical “disconnection” as a mechanism of age-related cognitive decline. Neurology 57:632–638PubMedCrossRefGoogle Scholar
  100. Ota M, Obata T, Akine Y, Ito H, Ikehira H, Asada T, Suhara T (2006) Age-related degeneration of corpus callosum measured with diffusion tensor imaging. Neuroimage 31:1445–1452. doi: 10.1016/j.neuroimage.2006.02.008 PubMedCrossRefGoogle Scholar
  101. Ota M, Yasuno F, Ito H, Seki C, Nozaki S, Asada T, Suhara T (2006) Age-related decline of dopamine synthesis in the living human brain measured by positron emission tomography with L-[beta-11C]DOPA. Life Sci 79:730–736. doi: 10.1016/j.lfs.2006.02.017 PubMedCrossRefGoogle Scholar
  102. Pakkenberg B, Gundersen HJ (1997) Neocortical neuron number in humans: effect of sex and age. J Comp Neurol 384:312–320PubMedCrossRefGoogle Scholar
  103. Palmer AM, Robichaud PJ, Reiter CT (1994) The release and uptake of excitatory amino acids in rat brain: effect of aging and oxidative stress. Neurobiol Aging 15:103–111PubMedCrossRefGoogle Scholar
  104. Pedigo NW Jr, Polk DM (1985) Reduced muscarinic receptor plasticity in frontal cortex of aged rats after chronic administration of cholinergic drugs. Life Sci 37:1443–1449PubMedCrossRefGoogle Scholar
  105. Peiffer AM, Shi L, Olson J, Brunso-Bechtold JK (2010) Differential effects of radiation and age on diffusion tensor imaging in rats. Brain Res 1351:23–31. doi: 10.1016/j.brainres.2010.06.049 PubMedCrossRefGoogle Scholar
  106. Peters A, Sethares C (2003) Is there remyelination during aging of the primate central nervous system? J Comp Neurol 460:238–254. doi: 10.1002/cne.10639 PubMedCrossRefGoogle Scholar
  107. Peters A, Moss MB, Sethares C (2000) Effects of aging on myelinated nerve fibers in monkey primary visual cortex. J Comp Neurol 419:364–376PubMedCrossRefGoogle Scholar
  108. Peters A, Feldman ML, Vaughan DW (1983) The effect of aging on the neuronal population within area 17 of adult rat cerebral cortex. Neurobiol Aging 4:273–282PubMedCrossRefGoogle Scholar
  109. Phillips LH, Andres P (2010) The cognitive neuroscience of aging: new findings on compensation and connectivity. Cortex 46:421–424. doi: 10.1016/j.cortex.2010.01.005 PubMedCrossRefGoogle Scholar
  110. Rapp PR, Gallagher M (1996) Preserved neuron number in the hippocampus of aged rats with spatial learning deficits. Proc Natl Acad Sci USA 93:9926–9930PubMedCrossRefGoogle Scholar
  111. Rapp SR, Espeland MA, Shumaker SA, Henderson VW, Brunner RL, Manson JE, Gass ML, Stefanick ML, Lane DS, Hays J, Johnson KC, Coker LH, Dailey M, Bowen D, WHIMS Investigators (2003) Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 289:2663–2672. doi: 10.1001/jama.289.20.2663 PubMedCrossRefGoogle Scholar
  112. Rasmussen T, Schliemann T, Sorensen JC, Zimmer J, West MJ (1996) Memory impaired aged rats: no loss of principal hippocampal and subicular neurons. Neurobiol Aging 17:143–147PubMedCrossRefGoogle Scholar
  113. Raz N, Ghisletta P, Rodrigue KM, Kennedy KM, Lindenberger U (2010) Trajectories of brain aging in middle-aged and older adults: regional and individual differences. Neuroimage 51:501–511. doi: 10.1016/j.neuroimage.2010.03.020 PubMedCrossRefGoogle Scholar
  114. Raz N, Rodrigue KM (2006) Differential aging of the brain: patterns, cognitive correlates and modifiers. Neurosci Biobehav Rev 30:730–748. doi: 10.1016/j.neubiorev.2006.07.001 PubMedCrossRefGoogle Scholar
  115. Raz N, Lindenberger U, Rodrigue KM, Kennedy KM, Head D, Williamson A, Dahle C, Gerstorf D, Acker JD (2005) Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. Cereb Cortex 15:1676–1689. doi: 10.1093/cercor/bhi044 PubMedCrossRefGoogle Scholar
  116. Raz N, Rodrigue KM, Kennedy KM, Acker JD (2004) Hormone replacement therapy and age-related brain shrinkage: regional effects. Neuroreport 15:2531–2534PubMedCrossRefGoogle Scholar
  117. Raz N, Gunning FM, Head D, Dupuis JH, McQuain J, Briggs SD, Loken WJ, Thornton AE, Acker JD (1997) Selective aging of the human cerebral cortex observed in vivo: differential vulnerability of the prefrontal gray matter. Cereb Cortex 7:268–282PubMedCrossRefGoogle Scholar
  118. Resnick SM, Espeland MA, Jaramillo SA, Hirsch C, Stefanick ML, Murray AM, Ockene J, Davatzikos C (2009) Postmenopausal hormone therapy and regional brain volumes: the WHIMS-MRI Study. Neurology 72:135–142. doi: 10.1212/ PubMedCrossRefGoogle Scholar
  119. Resnick SM, Pham DL, Kraut MA, Zonderman AB, Davatzikos C (2003) Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain. J Neurosci 23:3295–3301PubMedGoogle Scholar
  120. Riddle DR, Sonntag WE, Lichtenwalner RJ (2003) Microvascular plasticity in aging. Ageing Res Rev 2:149–168PubMedCrossRefGoogle Scholar
  121. Rinne JO, Sahlberg N, Ruottinen H, Nagren K, Lehikoinen P (1998) Striatal uptake of the dopamine reuptake ligand [11C]beta-CFT is reduced in Alzheimer’s disease assessed by positron emission tomography. Neurology 50:152–156PubMedCrossRefGoogle Scholar
  122. Rinne JO, Lonnberg P, Marjamaki P (1990) Age-dependent decline in human brain dopamine D1 and D2 receptors. Brain Res 508:349–352PubMedCrossRefGoogle Scholar
  123. Robertson D, Craig M, van Amelsvoort T, Daly E, Moore C, Simmons A, Whitehead M, Morris R, Murphy D (2009) Effects of estrogen therapy on age-related differences in gray matter concentration. Climacteric 12:301–309. doi: 10.1080/13697130902730742 PubMedCrossRefGoogle Scholar
  124. Rubinow MJ, Hagerbaumer DA, Juraska JM (2009) The food-conditioned place preference task in adolescent, adult and aged rats of both sexes. Behav Brain Res 198:263–266. doi: 10.1016/j.bbr.2008.11.024 PubMedCrossRefGoogle Scholar
  125. Rubinow MJ, Juraska JM (2009) Neuron and glia numbers in the basolateral nucleus of the amygdala from preweaning through old age in male and female rats: a stereological study. J Comp Neurol 512:717–725. doi: 10.1002/cne.21924 PubMedCrossRefGoogle Scholar
  126. Ryberg C, Rostrup E, Stegmann MB, Barkhof F, Scheltens P, van Straaten EC, Fazekas F, Schmidt R, Ferro JM, Baezner H, Erkinjuntti T, Jokinen H, Wahlund LO, O’brien J, Basile AM, Pantoni L, Inzitari D, Waldemar G, LADIS study group (2007) Clinical significance of corpus callosum atrophy in a mixed elderly population. Neurobiol Aging 28:955–963. doi: 10.1016/j.neurobiolaging.2006.04.008 PubMedCrossRefGoogle Scholar
  127. Salat DH, Greve DN, Pacheco JL, Quinn BT, Helmer KG, Buckner RL, Fischl B (2009) Regional white matter volume differences in nondemented aging and Alzheimer’s disease. Neuroimage 44:1247–1258. doi: 10.1016/j.neuroimage.2008.10.030 PubMedCrossRefGoogle Scholar
  128. Salat DH, Tuch DS, Greve DN, van der Kouwe AJ, Hevelone ND, Zaleta AK, Rosen BR, Fischl B, Corkin S, Rosas HD, Dale AM (2005) Age-related alterations in white matter microstructure measured by diffusion tensor imaging. Neurobiol Aging 26:1215–1227. doi: 10.1016/j.neurobiolaging.2004.09.017 PubMedCrossRefGoogle Scholar
  129. Sanchez-Prieto J, Herrero I, Miras-Portugal MT, Mora F (1994) Unchanged exocytotic release of glutamic acid in cortex and neostriatum of the rat during aging. Brain Res Bull 33:357–359PubMedCrossRefGoogle Scholar
  130. Saransaari P, Oja SS (1995) Age-related changes in the uptake and release of glutamate and aspartate in the mouse brain. Mech Ageing Dev 81:61–71PubMedCrossRefGoogle Scholar
  131. Sargon MF, Denk CC, Celik HH, Surucu HS, Aldur MM (2007) Electron microscopic examination of the myelinated axons of corpus callosum. in perfused young and old rats. Int J Neurosci 117:999–1010. doi: 10.1080/00207450600934382 PubMedCrossRefGoogle Scholar
  132. Saura J, Andres N, Andrade C, Ojuel J, Eriksson K, Mahy N (1997) Biphasic and region-specific MAO-B response to aging in normal human brain. Neurobiol Aging 18:497–507PubMedCrossRefGoogle Scholar
  133. Scahill RI, Frost C, Jenkins R, Whitwell JL, Rossor MN, Fox NC (2003) A longitudinal study of brain volume changes in normal aging using serial registered magnetic resonance imaging. Arch Neurol 60:989–994. doi: 10.1001/archneur.60.7.989 PubMedCrossRefGoogle Scholar
  134. Schliebs R, Arendt T (2006) The significance of the cholinergic system in the brain during aging and in Alzheimer’s disease. J Neural Transm 113:1625–1644. doi: 10.1007/s00702-006-0579-2 PubMedCrossRefGoogle Scholar
  135. Seeman P, Bzowej NH, Guan HC, Bergeron C, Becker LE, Reynolds GP, Bird ED, Riederer P, Jellinger K, Watanabe S (1987) Human brain dopamine receptors in children and aging adults. Synapse 1:399–404. doi: 10.1002/syn.890010503 PubMedCrossRefGoogle Scholar
  136. Severson JA, Marcusson J, Winblad B, Finch CE (1982) Age-correlated loss of dopaminergic binding sites in human basal ganglia. J Neurochem 39:1623–1631PubMedCrossRefGoogle Scholar
  137. Shi L, Pang H, Linville MC, Bartley AN, Argenta AE, Brunso-Bechtold JK (2006) Maintenance of inhibitory interneurons and boutons in sensorimotor cortex between middle and old age in Fischer 344 X Brown Norway rats. J Chem Neuroanat 32:46–53. doi: 10.1016/j.jchemneu.2006.04.001 PubMedCrossRefGoogle Scholar
  138. Shi L, Linville MC, Tucker EW, Sonntag WE, Brunso-Bechtold JK (2005) Differential effects of aging and insulin-like growth factor-1 on synapses in CA1 of rat hippocampus. Cereb Cortex 15:571–577. doi: 10.1093/cercor/bhh158 PubMedCrossRefGoogle Scholar
  139. Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, Fillit H, Stefanick ML, Hendrix SL, Lewis CE, Masaki K, Coker LH, Women’s Health Initiative Memory Study (2004) Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women’s Health Initiative Memory Study. JAMA 291:2947–2958. doi: 10.1001/jama.291.24.2947 PubMedCrossRefGoogle Scholar
  140. Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, Hendrix SL, Jones BN 3rd, Assaf AR, Jackson RD, Kotchen JM, Wassertheil-Smoller S, Wactawski-Wende J, WHIMS Investigators (2003) Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 289:2651–2662. doi: 10.1001/jama.289.20.2651 PubMedCrossRefGoogle Scholar
  141. Simic G, Kostovic I, Winblad B, Bogdanovic N (1997) Volume and number of neurons of the human hippocampal formation in normal aging and Alzheimer’s disease. J Comp Neurol 379:482–494PubMedCrossRefGoogle Scholar
  142. Smith DE, Rapp PR, McKay HM, Roberts JA, Tuszynski MH (2004) Memory impairment in aged primates is associated with focal death of cortical neurons and atrophy of subcortical neurons. J Neurosci 24:4373–4381. doi: 10.1523/JNEUROSCI.4289-03.2004 PubMedCrossRefGoogle Scholar
  143. Smith TD, Adams MM, Gallagher M, Morrison JH, Rapp PR (2000) Circuit-specific alterations in hippocampal synaptophysin immunoreactivity predict spatial learning impairment in aged rats. J Neurosci 20:6587–6593PubMedGoogle Scholar
  144. Smith YR, Minoshima S, Kuhl DE, Zubieta JK (2001) Effects of long-term hormone therapy on cholinergic synaptic concentrations in healthy postmenopausal women. J Clin Endocrinol Metab 86:679–684PubMedCrossRefGoogle Scholar
  145. Soghomonian JJ, Sethares C, Peters A (2010) Effects of age on axon terminals forming axosomatic and axodendritic inhibitory synapses in prefrontal cortex. Neuroscience 168:74–81. doi: 10.1016/j.neuroscience.2010.03.020 PubMedCrossRefGoogle Scholar
  146. Sowell ER, Peterson BS, Thompson PM, Welcome SE, Henkenius AL, Toga AW (2003) Mapping cortical change across the human life span. Nat Neurosci 6:309–315. doi: 10.1038/nn1008 PubMedCrossRefGoogle Scholar
  147. Spencer RL, O’Steen WK, McEwen BS (1995) Water maze performance of aged Sprague-Dawley rats in relation to retinal morphologic measures. Behav Brain Res 68:139–150PubMedCrossRefGoogle Scholar
  148. Stroessner-Johnson HM, Rapp PR, Amaral DG (1992) Cholinergic cell loss and hypertrophy in the medial septal nucleus of the behaviorally characterized aged rhesus monkey. J Neurosci 12:1936–1944PubMedGoogle Scholar
  149. Suhara T, Fukuda H, Inoue O, Itoh T, Suzuki K, Yamasaki T, Tateno Y (1991) Age-related changes in human D1 dopamine receptors measured by positron emission tomography. Psychopharmacology (Berl) 103:41–45CrossRefGoogle Scholar
  150. Sullivan EV, Pfefferbaum A, Adalsteinsson E, Swan GE, Carmelli D (2002) Differential rates of regional brain change in callosal and ventricular size: a 4-year longitudinal MRI study of elderly men. Cereb Cortex 12:438–445PubMedCrossRefGoogle Scholar
  151. Takei N, Nihonmatsu I, Kawamura H (1989) Age-related decline of acetylcholine release evoked by depolarizing stimulation. Neurosci Lett 101:182–186PubMedCrossRefGoogle Scholar
  152. Terry RD, DeTeresa R, Hansen LA (1987) Neocortical cell counts in normal human adult aging. Ann Neurol 21:530–539. doi: 10.1002/ana.410210603 PubMedCrossRefGoogle Scholar
  153. Tigges J, Herndon JG, Rosene DL (1996) Preservation into old age of synaptic number and size in the supragranular layer of the dentate gyrus in rhesus monkeys. Acta Anat (Basel) 157:63–72CrossRefGoogle Scholar
  154. Uemura E (1985) Age-related changes in the subiculum of Macaca mulatta: dendritic branching pattern. Exp Neurol 87:412–427PubMedCrossRefGoogle Scholar
  155. van Dyck CH, Seibyl JP, Malison RT, Laruelle M, Wallace E, Zoghbi SS, Zea-Ponce Y, Baldwin RM, Charney DS, Hoffer PB (1995) Age-related decline in striatal dopamine transporter binding with iodine-123-beta-CITSPECT. J Nucl Med 36:1175–1181PubMedGoogle Scholar
  156. Vatassery GT, Lai JC, Smith WE, Quach HT (1998) Aging is associated with a decrease in synaptosomal glutamate uptake and an increase in the susceptibility of synaptosomal vitamin E to oxidative stress. Neurochem Res 23:121–125PubMedCrossRefGoogle Scholar
  157. Vaughan DW (1977) Age-related deterioration of pyramidal cell basal dendrites in rat auditory cortex. J Comp Neurol 171:501–515. doi: 10.1002/cne.901710406 PubMedCrossRefGoogle Scholar
  158. Walhovd KB, Westlye LT, Amlien I, Espeseth T, Reinvang I, Raz N, Agartz I, Salat DH, Greve DN, Fischl B, Dale AM, Fjell AM (2009) Consistent neuroanatomical age-related volume differences across multiple samples. Neurobiol Aging. doi: 10.1016/j.neurobiolaging.2009.05.013
  159. Walker LC, Kitt CA, Struble RG, Wagster MV, Price DL, Cork LC (1988) The neural basis of memory decline in aged monkeys. Neurobiol Aging 9:657–666PubMedCrossRefGoogle Scholar
  160. Wallace M, Frankfurt M, Arellanos A, Inagaki T, Luine V (2007) Impaired recognition memory and decreased prefrontal cortex spine density in aged female rats. Ann N Y Acad Sci 1097:54–57. doi: 10.1196/annals.1379.026 PubMedCrossRefGoogle Scholar
  161. Wang Y, Chan GL, Holden JE, Dobko T, Mak E, Schulzer M, Huser JM, Snow BJ, Ruth TJ, Calne DB, Stoessl AJ (1998) Age-dependent decline of dopamine D1 receptors in human brain: a PET study. Synapse 30:56–61PubMedCrossRefGoogle Scholar
  162. West MJ (1993) Regionally specific loss of neurons in the aging human hippocampus. Neurobiol Aging 14:287–293PubMedCrossRefGoogle Scholar
  163. Wheeler DD, Ondo JG (1986) Endogenous GABA concentration in cortical synaptosomes from young and aged rats. Exp Gerontol 21:79–85PubMedCrossRefGoogle Scholar
  164. Wise PM, Ratner A (1980) Effect of ovariectomy on plasma LH, FSH, estradiol, and progesterone and medial basal hypothalamic LHRH concentrations old and young rats. Neuroendocrinology 30:15–19PubMedCrossRefGoogle Scholar
  165. Wong TP, Marchese G, Casu MA, Ribeiro-da-Silva A, Cuello AC, De Koninck Y (2006) Imbalance towards inhibition as a substrate of aging-associated cognitive impairment. Neurosci Lett 397:64–68. doi: 10.1016/j.neulet.2005.11.055 PubMedCrossRefGoogle Scholar
  166. Wong TP, Marchese G, Casu MA, Ribeiro-da-Silva A, Cuello AC, De Koninck Y (2000) Loss of presynaptic and postsynaptic structures is accompanied by compensatory increase in action potential-dependent synaptic input to layer V neocortical pyramidal neurons in aged rats. J Neurosci 20:8596–8606PubMedGoogle Scholar
  167. Wong TP, Campbell PM, Ribeiro-da-Silva A, Cuello AC (1998) Synaptic numbers across cortical laminae and cognitive performance of the rat during ageing. Neuroscience 84:403–412PubMedCrossRefGoogle Scholar
  168. Yang S, Li C, Lu W, Zhang W, Wang W, Tang Y (2009) The myelinated fiber changes in the white matter of aged female Long-Evans rats. J Neurosci Res 87:1582–1590. doi: 10.1002/jnr.21986 PubMedCrossRefGoogle Scholar
  169. Yassa MA, Muftuler LT, Stark CE (2010) Ultrahigh-resolution microstructural diffusion tensor imaging reveals perforant path degradation in aged humans in vivo. Proc Natl Acad Sci USA 107:12687–12691. doi: 10.1073/pnas.1002113107 PubMedCrossRefGoogle Scholar
  170. Yates MA, Markham JA, Anderson SE, Morris JR, Juraska JM (2008) Regional variability in age-related loss of neurons from the primary visual cortex and medial prefrontal cortex of male and female rats. Brain Res 1218:1–12. doi: 10.1016/j.brainres.2008.04.055 PubMedCrossRefGoogle Scholar
  171. Yates MA, Juraska JM (2007) Increases in size and myelination of the rat corpus callosum during adulthood are maintained into old age. Brain Res 1142:13–18. doi: 10.1016/j.brainres.2007.01.043 PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of Psychology and Program in NeuroscienceUniversity of IllinoisChampaignUSA
  2. 2.Department of PsychologyUniversity of IllinoisChampaignUSA

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