title: The effects of chronic alcoholism on cell proliferation in the human brain.
abstract: Neurogenesis continues in the human subventricular zone and to a lesser extent in the hippocampal subgranular zone throughout life. Subventricular zone-derived neuroblasts migrate to the olfactory bulb where survivors become integrated as interneurons and are postulated to contribute to odor discrimination. Adult neurogenesis is dysregulated in many neurological, neurovascular and neurodegenerative diseases. Alcohol abuse can result in a neurodegenerative condition called alcohol-related brain damage. Alcohol-related brain damage manifests clinically as cognitive dysfunction and the loss of smell sensation (hyposmia) and pathologically as generalized white matter atrophy and focal neuronal loss. The exact mechanism linking chronic alcohol intoxication with alcohol-related brain damage remains largely unknown but rodent models suggest that decreased neurogenesis is an important component. We investigated this idea by comparing proliferative events in the subventricular zone and olfactory bulb of a well-characterized cohort of 15 chronic alcoholics and 16 age-matched controls. In contrast to the findings in animal models there was no difference in the number of proliferative cell nuclear antigen-positive cells in the subventricular zone of alcoholics (mean±SD=28.7±20.0) and controls (27.6±18.9, p=1.0). There were also no differences in either the total (p=0.89) or proliferative cells (p=0.98) in the granular cell layer of the olfactory bulb. Our findings show that chronic alcohol consumption does not affect cell proliferation in the human SVZ or olfactory bulb. In fact only microglial proliferation could be demonstrated in the latter. Therefore neurogenic deficits are unlikely to contribute to hyposmia in chronic alcoholics.
authors.affiliation: Discipline of Pathology, Sydney Medical School, The University of Sydney, NSW 2006, Australia. g.sutherland@sydney.edu.au
authors.forename: G T
authors.initials: GT
authors.lastname: Sutherland
authors.forename: P J
authors.initials: PJ
authors.lastname: Sheahan
authors.forename: J
authors.initials: J
authors.lastname: Matthews
authors.forename: C V P
authors.initials: CV
authors.lastname: Dennis
authors.forename: D S
authors.initials: DS
authors.lastname: Sheedy
authors.forename: T
authors.initials: T
authors.lastname: McCrossin
authors.forename: M A
authors.initials: MA
authors.lastname: Curtis
authors.forename: J J
authors.initials: JJ
authors.lastname: Kril
mesh_terms: D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D002452:Cell Count; D049109:Cell Proliferation; D002908:Chronic Disease; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D020547:Lateral Ventricles / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009830:Olfactory Bulb / Q000473:pathology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D010751:Phosphopyruvate Hydratase
keywords: Adult neurogenesis; Chronic alcoholism; Human brain tissue; Proliferation
references.citation: J Histochem Cytochem. 1997 Mar;45(3):327-43
references.pmid: 9071315
references.citation: J Neurosci. 2010 Sep 15;30(37):12252-62
references.pmid: 20844121
references.citation: Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14895-900
references.pmid: 8962152
references.citation: Biol Psychiatry. 2008 Aug 1;64(3):192-202
references.pmid: 18374900
references.citation: Wien Klin Wochenschr. 2005 Jan;117(1-2):26-30
references.pmid: 15986587
references.citation: Proc Natl Acad Sci U S A. 2011 May 17;108(20):8479-84
references.pmid: 21536899
references.citation: J Neurosci. 2009 Sep 30;29(39):12302-14
references.pmid: 19793989
references.citation: J Neurochem. 2002 Dec;83(5):1087-93
references.pmid: 12437579
references.citation: Nat Neurosci. 2004 Jul;7(7):726-35
references.pmid: 15195095
references.citation: J Immunol Methods. 1988 Apr 22;109(1):49-59
references.pmid: 2895795
references.citation: Br Med J (Clin Res Ed). 1987 Feb 28;294(6571):534-6
references.pmid: 3103762
references.citation: Neurobiol Dis. 2006 Oct;24(1):1-14
references.pmid: 16814555
references.citation: Nat Neurosci. 2008 Oct;11(10):1153-61
references.pmid: 18758458
references.citation: Cell Prolif. 1992 Jan;25(1):31-40
references.pmid: 1540682
references.citation: Neuroscience. 1997 Aug;79(4):983-98
references.pmid: 9219961
references.citation: Eur J Neurosci. 2005 May;21(10):2711-20
references.pmid: 15926919
references.citation: Exp Neurol. 2008 Apr;210(2):349-58
references.pmid: 18190912
references.citation: Neuroscience. 2011 Dec 29;199:577-88
references.pmid: 21946006
references.citation: Alcohol Clin Exp Res. 2003 Mar;27(3):432-9
references.pmid: 12658108
references.citation: Neuroimage. 2001 Jul;14(1 Pt 1):7-20
references.pmid: 11525339
references.citation: Int J Neuropsychopharmacol. 2010 Jun;13(5):583-93
references.pmid: 20334723
references.citation: Neurosci Lett. 2005 Jul 22-29;383(1-2):33-8
references.pmid: 15936508
references.citation: Neuropathol Appl Neurobiol. 2003 Oct;29(5):503-10
references.pmid: 14507342
references.citation: Cell Res. 2011 Nov;21(11):1534-50
references.pmid: 21577236
references.citation: Genes Brain Behav. 2008 Feb;7 Suppl 1:28-42
references.pmid: 18184368
references.citation: Science. 1994 May 20;264(5162):1145-8
references.pmid: 8178174
references.citation: Nat Rev Neurosci. 2007 Sep;8(9):712-23
references.pmid: 17704813
references.citation: Neuropharmacology. 2010 May;58(6):940-9
references.pmid: 20138063
references.citation: Mol Brain. 2011 Jul 07;4:29
references.pmid: 21736737
references.citation: Trends Neurosci. 2001 Jan;24(1):11-7
references.pmid: 11163882
references.citation: J Anat. 2007 Jul;211(1):117-24
references.pmid: 17553102
references.citation: J Neurol Neurosurg Psychiatry. 1988 Jan;51(1):124-7
references.pmid: 3351512
references.citation: Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7919-24
references.pmid: 12792022
references.citation: Hippocampus. 1997;7(1):78-87
references.pmid: 9138671
references.citation: Ann N Y Acad Sci. 2009 Jul;1170:239-54
references.pmid: 19686142
references.citation: Aging Cell. 2010 Jun;9(3):313-26
references.pmid: 20121722
references.citation: Brain Pathol. 2013 May;23(3):263-73
references.pmid: 22994884
references.citation: Alcohol Clin Exp Res. 2005 Aug;29(8):1504-13
references.pmid: 16156047
references.citation: J Cell Biol. 1987 Oct;105(4):1549-54
references.pmid: 2889739
references.citation: PLoS One. 2011;6(8):e23190
references.pmid: 21858026
references.citation: Acta Neuropathol. 2010 Jun;119(6):723-35
references.pmid: 20383714
references.citation: Alcohol Alcohol. 2009 Mar-Apr;44(2):115-27
references.pmid: 18940959
references.citation: J Neurosci. 2006 Dec 13;26(50):13114-9
references.pmid: 17167100
references.citation: J Neurosci. 2004 Sep 22;24(38):8354-65
references.pmid: 15385618
references.citation: Nature. 2011 Sep 28;478(7369):382-6
references.pmid: 21964341
references.citation: Neuroscience. 2005;132(3):777-88
references.pmid: 15837138
references.citation: J Clin Exp Neuropsychol. 1987 Dec;9(6):650-64
references.pmid: 2961789
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):9023-7
references.pmid: 12853570
references.citation: J Comp Neurol. 2007 Apr 20;501(6):825-36
references.pmid: 17311323
references.citation: Hippocampus. 2006;16(3):287-95
references.pmid: 16421863
references.citation: Brain. 2011 Nov;134(Pt 11):3249-63
references.pmid: 22075520
references.citation: J Comp Neurol. 1969 Dec;137(4):433-57
references.pmid: 5361244
references.citation: J Clin Exp Neuropsychol. 2006 Nov;28(8):1373-80
references.pmid: 17050264
references.citation: Cell Tissue Bank. 2008 Sep;9(3):205-16
references.pmid: 18543078
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13198-202
references.pmid: 16924107
references.citation: Brain Inj. 2011;25(5):503-10
references.pmid: 21456999
references.citation: Histol Histopathol. 1989 Apr;4(2):183-92
references.pmid: 2520455
references.citation: Nat Med. 1998 Nov;4(11):1313-7
references.pmid: 9809557
references.citation: Nature. 2011 Oct 19;478(7369):333-4
references.pmid: 22012389
references.citation: Science. 2007 Mar 2;315(5816):1243-9
references.pmid: 17303719
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):11104-9
references.pmid: 20534463
references.citation: J Comp Neurol. 1993 Jul 22;333(4):519-30
references.pmid: 7690371
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17980-5
references.pmid: 19815505
references.citation: J Histochem Cytochem. 2008 Mar;56(3):201-21
references.pmid: 17998570
references.citation: Neuron. 2012 May 24;74(4):634-9
references.pmid: 22632721
references.citation: Alcohol Clin Exp Res. 2010 Mar 1;34(3):443-50
references.pmid: 20028356
references.citation: Biochem Soc Trans. 2009 Jun;37(Pt 3):605-13
references.pmid: 19442257
references.citation: J Pathol. 1990 Dec;162(4):285-94
references.pmid: 1981239
references.citation: Int J Environ Res Public Health. 2010 Apr;7(4):1540-57
references.pmid: 20617045
references.citation: Eur J Neurosci. 2008 Dec;28(11):2254-65
references.pmid: 19046368
references.citation: Drug Alcohol Depend. 2013 Jun 1;130(1-3):1-12
references.pmid: 23279925
references.citation: Biol Psychiatry. 2009 Apr 15;65(8):680-90
references.pmid: 19103436
references.citation: Brain Res Dev Brain Res. 2004 Jul 19;151(1-2):159-68
references.pmid: 15246702