title: Wake-active neurons across aging and neurodegeneration: a potential role for sleep disturbances in promoting disease.
abstract: Sleep/wake disturbance is a feature of almost all common age-related neurodegenerative diseases. Although the reason for this is unknown, it is likely that this inability to maintain sleep and wake states is in large part due to declines in the number and function of wake-active neurons, populations of cells that fire only during waking and are silent during sleep. Consistent with this, many of the brain regions that are most susceptible to neurodegeneration are those that are necessary for wake maintenance and alertness. In the present review, these wake-active populations are systematically assessed in terms of their observed pathology across aging and several neurodegenerative diseases, with implications for future research relating sleep and wake disturbances to aging and age-related neurodegeneration.
authors: Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
authors: Anna L
authors: AL
authors: Stern
authors: Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
authors: Nirinjini
authors: N
authors: Naidoo
keywords: Aging; Daytime sleepiness; Fragmentation; Neurodegeneration; Sleep
references: Nat Clin Pract Neurol. 2008 May;4(5):254-66
references: 18398415
references: Sleep. 2012 Sep 01;35(9):1201-7
references: 22942498
references: Acta Neuropathol. 2001 Mar;101(3):256-70
references: 11307626
references: Nat Neurosci. 2010 Dec;13(12):1526-33
references: 21037585
references: Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10744-9
references: 15249681
references: Neurosci Lett. 1992 Jul 6;141(1):9-12
references: 1508406
references: Front Pharmacol. 2014 Feb 12;5:16
references: 24575043
references: Sleep Med. 2010 Apr;11(4):372-7
references: 20219426
references: Sleep Med Rev. 2013 Oct;17(5):367-75
references: 23481545
references: Brain Res. 1990 Feb 26;510(1):104-7
references: 1691042
references: Sleep. 1993 Jan;16(1):40-81
references: 8456235
references: Am J Geriatr Psychiatry. 2006 Oct;14(10):860-6
references: 17001025
references: Neuropsychologia. 2014 Jan;53:54-63
references: 24269297
references: J Neurosci. 2014 Mar 19;34(12):4418-31
references: 24647961
references: Behav Brain Res. 2011 Aug 10;221(2):555-63
references: 21145918
references: PLoS One. 2013 Nov 21;8(11):e81233
references: 24278399
references: JAMA Neurol. 2013 Dec;70(12):1544-51
references: 24145819
references: Drugs Aging. 2012 Nov;29(11):911-23
references: 23044640
references: Neuropathol Appl Neurobiol. 2000 Aug;26(4):347-55
references: 10931368
references: J Pharmacol Exp Ther. 2011 Jan;336(1):38-46
references: 20864505
references: Cell Tissue Res. 2004 Oct;318(1):121-34
references: 15338272
references: PLoS One. 2013;8(1):e53814
references: 23326515
references: Peptides. 2005 Dec;26(12):2590-6
references: 15951059
references: Clin Neuropathol. 1997 Jan-Feb;16(1):23-6
references: 9020390
references: J Neurol. 2013 May;260(5):1433-40
references: 23589196
references: Exp Gerontol. 2013 Jul;48(7):603-7
references: 22910064
references: Parkinsonism Relat Disord. 2009 Dec;15 Suppl 3:S101-4
references: 20082966
references: Brain Res. 2002 Sep 6;948(1-2):47-55
references: 12383954
references: Neurosci Lett. 2010 Mar 12;472(1):29-32
references: 20117171
references: J Neurol. 2014 Oct;261(10):1939-48
references: 25059393
references: Am J Geriatr Psychiatry. 2007 Apr;15(4):344-50
references: 17384317
references: Cereb Cortex. 1994 Mar-Apr;4(2):138-50
references: 8038565
references: Semin Neurol. 2014 Apr;34(2):189-201
references: 24963678
references: Prog Neuropsychopharmacol Biol Psychiatry. 2005 Feb;29(2):297-303
references: 15694238
references: Exp Neurol. 2000 May;163(1):20-30
references: 10785440
references: Front Neurol. 2012 May 15;3:69
references: 22615706
references: Neurosci Lett. 1988 Dec 19;95(1-3):93-6
references: 3226627
references: Biol Psychiatry. 2012 May 1;71(9):805-13
references: 21816388
references: Nat Neurosci. 2013 Mar;16(3):357-64
references: 23354332
references: Clin Geriatr Med. 2014 Aug;30(3):591-627
references: 25037297
references: Lancet Neurol. 2013 Jan;12(1):105-18
references: 23237905
references: Sleep Med Rev. 2011 Aug;15(4):269-81
references: 21459634
references: Ann Neurol. 2013 Dec;74(6):794-804
references: 24006291
references: Psychopharmacology (Berl). 2005 May;179(3):673-7
references: 15551121
references: Neurobiol Aging. 1992 Mar-Apr;13(2):201-15
references: 1355858
references: Eur J Neurol. 2009 Mar;16(3):317-23
references: 19170747
references: J Chem Neuroanat. 1994 Aug;7(3):185-90
references: 7848573
references: Neuron. 2000 Sep;27(3):469-74
references: 11055430
references: Ann Neurol. 2004 Jun;55(6):815-28
references: 15174015
references: J Neuropsychiatry Clin Neurosci. 2002 Spring;14(2):223-36; discussion 222
references: 11983801
references: J Sleep Res. 2005 Sep;14(3):311-7
references: 16120107
references: J Neurosci. 2010 Oct 6;30(40):13254-64
references: 20926651
references: Neurosci Lett. 1993 Feb 5;150(1):71-4
references: 7682308
references: Science. 2009 Nov 13;326(5955):1005-7
references: 19779148
references: Neurology. 2005 Nov 8;65(9):1442-6
references: 16275833
references: Behav Brain Res. 2001 Oct 15;124(2):213-33
references: 11640975
references: Magn Reson Med Sci. 2006 Dec;5(4):197-200
references: 17332710
references: Cereb Cortex. 2010 Jul;20(7):1685-95
references: 19889714
references: J Neurosci. 2011 Jul 20;31(29):10529-39
references: 21775598
references: Ann Neurol. 2000 Sep;48(3):344-53
references: 10976641
references: Sleep Med. 2014 Jun;15(6):647-53
references: 24841108
references: J Neurosci. 2006 Jan 4;26(1):193-202
references: 16399687
references: J Sleep Res. 2007 Dec;16(4):372-80
references: 18036082
references: Synapse. 2012 May;66(5):445-52
references: 22213437
references: Neurobiol Aging. 2012 Nov;33(11):2585-98
references: 22284987
references: Neuroscience. 2010 Sep 1;169(3):1115-26
references: 20542093
references: Neuroreport. 1992 May;3(5):433-6
references: 1633281
references: Mov Disord. 2014 Mar;29(3):410-5
references: 24488760
references: Neurosci Lett. 1993 Mar 19;151(2):196-9
references: 8506080
references: Cell. 1999 Aug 6;98(3):365-76
references: 10458611
references: Brain Res. 1984 Oct 8;311(1):51-6
references: 6488044
references: Ann Neurol. 1985 Feb;17(2):163-70
references: 3883886
references: Compr Gerontol A. 1988 Oct;2(3):114-9
references: 2906817
references: Front Physiol. 2012 Jul 16;3:263
references: 22934019
references: Prog Brain Res. 2004;145:179-96
references: 14650916
references: Neuropsychopharmacology. 2011 Jan;36(1):52-73
references: 20668433
references: Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9965-70
references: 11493714
references: Exp Neurol. 2000 Dec;166(2):363-75
references: 11085901
references: Clin Interv Aging. 2014 Jun 18;9:947-61
references: 24971004
references: Expert Opin Drug Saf. 2014 Jun;13(6):759-74
references: 24845946
references: Am J Physiol. 1999 Nov;277(5):R1488-92
references: 10564223
references: Dement Geriatr Cogn Disord. 2012;33(1):50-8
references: 22415141
references: J Clin Endocrinol Metab. 2005 Aug;90(8):4510-5
references: 15941867
references: Int J Cell Biol. 2013;2013:797914
references: 24348565
references: Clin Neuropathol. 2011 May-Jun;30(3):104-10
references: 21545773
references: Int J Neurosci. 2006 Jul;116(7):775-826
references: 16861147
references: Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):322-7
references: 9419374
references: Sleep. 2013 Jul 01;36(7):1027-1032
references: 23814339
references: Behav Brain Res. 2011 Aug 10;221(2):499-504
references: 21238497
references: J Neurosci. 2006 Feb 1;26(5):1343-54
references: 16452658
references: Brain Res. 2013 Sep 19;1531:9-16
references: 23916734
references: Aging (Milano). 1998 Aug;10(4):308-15
references: 9825022
references: Brain Res. 2003 Oct 24;988(1-2):84-96
references: 14519529
references: Am J Respir Crit Care Med. 2005 Oct 1;172(7):921-9
references: 15994465
references: Dement Geriatr Cogn Disord. 2008;25(4):372-9
references: 18354253
references: Brain. 2007 Nov;130(Pt 11):2770-88
references: 17412731
references: Brain. 2007 Jun;130(Pt 6):1586-95
references: 17491094
references: Brain. 2010 Jul;133(Pt 7):2058-68
references: 20558417
references: Nat Neurosci. 2014 Jun;17(6):832-40
references: 24816140
references: Neurobiol Aging. 2010 Dec;31(12):2103-14
references: 19152986
references: Curr Biol. 2004 Dec 29;14(24):R1038-9
references: 15620633
references: Sleep. 2014 Jan 01;37(1):51-64
references: 24470695
references: J Physiol Sci. 2013 Mar;63(2):95-101
references: 23086726
references: Neuroreport. 2010 Aug 4;21(11):756-60
references: 20531237
references: J Neurosci. 2013 Jul 31;33(31):12557-68
references: 23904594
references: JAMA Neurol. 2014 Apr;71(4):505-8
references: 24493463
references: Neurobiol Aging. 1997 Jul-Aug;18(4):393-9
references: 9330970
references: Sci Transl Med. 2012 Apr 4;4(128):128ra41
references: 22491951
references: Nature. 2006 May 25;441(7092):513-7
references: 16724068
references: Neurology. 1992 Jul;42(7 Suppl 6):83-93; discussion 93-4
references: 1630644
references: Neurology. 2006 Apr 11;66(7):1111-3
references: 16606932
references: Gerontology. 2014;60(5):448-57
references: 24732109
references: Behav Brain Funct. 2010 Oct 21;6:62
references: 20964843
references: Brain Res. 1999 Apr 24;826(1):143-7
references: 10216207
references: J Sleep Res. 2010 Dec;19(4):620-3
references: 20846244
references: J Neurosci. 2005 Apr 20;25(16):4127-30
references: 15843615
references: Sleep. 2006 Oct;29(10):1327-36
references: 17068987
references: Neuroimage. 2010 Feb 15;49(4):2933-9
references: 19941962
references: Neurobiol Aging. 2007 Aug;28(8):1286-95
references: 16870307
references: Prog Neurobiol. 2012 Oct;99(1):15-41
references: 22766041
references: Eur J Neurol. 2012 May;19(5):760-3
references: 22233269
references: J Pharmacol Sci. 2010;114(4):444-53
references: 21135511
references: J Neuropathol Exp Neurol. 2011 Nov;70(11):960-9
references: 22002422
references: N Engl J Med. 2010 Mar 11;362(10):953-4
references: 20220193
references: Neurosci Lett. 2003 Jul 3;344(3):212-4
references: 12812843
references: Sleep Med Rev. 2015 Feb;19:29-38
references: 24846773
references: Brain. 1995 Feb;118 ( Pt 1):131-43
references: 7894999
references: Science. 2013 Oct 18;342(6156):373-7
references: 24136970
references: Brain. 2007 Jun;130(Pt 6):1577-85
references: 17470494
references: Nature. 2007 Nov 15;450(7168):420-4
references: 17943086
references: Neuropsychopharmacology. 1997 Aug;17(2):72-81
references: 9252982
references: J Neurol Neurosurg Psychiatry. 1979 Jul;42(7):640-1
references: 479903
references: J Alzheimers Dis. 2014;38(1):85-91
references: 24077430
references: Expert Rev Neurother. 2010 Jul;10(7):1101-15
references: 20586691
references: Cell. 1999 Aug 20;98(4):437-51
references: 10481909
references: Neurology. 2013 Mar 26;80(13):1202-8
references: 23486878
references: J Pineal Res. 2006 Nov;41(4):313-23
references: 17014688
references: Neuroreport. 2007 Dec 3;18(18):1895-9
references: 18007182
references: Aging Cell. 2011 Aug;10(4):640-9
references: 21388495
references: Neurology. 2009 Jul 14;73(2):106-12
references: 19597132
references: Curr Neuropharmacol. 2008 Sep;6(3):235-53
references: 19506723
references: Neuroscience. 2015 Jan 22;284:217-224
references: 25286384
references: Sleep. 2004 Nov 1;27(7):1255-73
references: 15586779
references: Neurobiol Dis. 2009 Sep;35(3):415-25
references: 19524671
references: Neurobiol Aging. 2007 Mar;28(3):327-35
references: 16574280
references: Neuropathology. 2011 Feb;31(1):71-6
references: 20573033
references: Neurobiol Aging. 2012 Aug;33(8):1642-50
references: 21546124
references: Neurosci Biobehav Rev. 2013 Dec;37(10 Pt 2):2676-88
references: 24035740
references: Sleep Med. 2013 Aug;14(8):744-8
references: 23347909
references: Maturitas. 2013 Nov;76(3):247-52
references: 23746664
references: J Neurosci. 1998 Dec 1;18(23):9996-10015
references: 9822755
references: J Neurosci Res. 1992 Jan;31(1):103-11
references: 1613816
references: Front Neurol. 2012 Jul 26;3:118
references: 22855682
references: J Neurol Neurosurg Psychiatry. 2011 Aug;82(8):839-42
references: 21217159
references: J Neurosci. 2007 Sep 12;27(37):10060-71
references: 17855620
references: Brain Pathol. 2015 Mar;25(2):121-35
references: 24995389
references: Neurobiol Aging. 2012 Jul;33(7):1343-4
references: 21371786
references: Neuroscience. 2011 Mar 31;178:82-8
references: 21262323
references: Psychopharmacology (Berl). 2008 Mar;196(4):603-10
references: 18026720
references: Acta Neuropathol. 1999 Aug;98(2):186-96
references: 10442559
references: Front Aging Neurosci. 2014 May 06;6:82
references: 24834052
references: Ann Neurol. 2008 Nov;64(5):485-91
references: 19067353
references: Brain. 2005 Apr;128(Pt 4):896-905
references: 15689356
references: J Neurochem. 2005 Aug;94(3):828-38
references: 16033425
references: Curr Biol. 2008 Aug 5;18(15):1118-23
references: 18656358
references: J Sleep Res. 2013 Oct;22(5):535-41
references: 23560612
references: Arch Neurol. 2003 Mar;60(3):337-41
references: 12633144
references: Am J Alzheimers Dis Other Demen. 2013 Sep;28(6):606-11
references: 23813609
references: J Alzheimers Dis. 2012;29(1):125-32
references: 22207004
references: Neuroreport. 2001 Mar 26;12(4):669-71
references: 11277560