Alcohol-related amnesia and dementia: animal models have revealed the contributions of different etiological factors on neuropathology, neurochemical dysfunction and cognitive impairment.
Chronic alcoholism is associated with impaired cognitive functioning. Over 75% of autopsied chronic alcoholics have significant brain damage and over 50% of detoxified alcoholics display some degree of learning and memory impairment. However, the relative contributions of different etiological factors to the development of alcohol-related neuropathology and cognitive impairment are questioned. One reason for this quandary is that both alcohol toxicity and thiamine deficiency result in brain damage and cognitive problems. Two alcohol-related neurological disorders, alcohol-associated dementia and Wernicke-Korsakoff syndrome have been modeled in rodents. These pre-clinical models have elucidated the relative contributions of ethanol toxicity and thiamine deficiency to the development of dementia and amnesia. What is observed in these models--from repeated and chronic ethanol exposure to thiamine deficiency--is a progression of both neural and cognitive dysregulation. Repeated binge exposure to ethanol leads to changes in neural plasticity by reducing GABAergic inhibition and facilitating glutamatergic excitation, long-term chronic ethanol exposure results in hippocampal and cortical cell loss as well as reduced hippocampal neurotrophin protein content critical for neural survival, and thiamine deficiency results in gross pathological lesions in the diencephalon, reduced neurotrophic protein levels, and neurotransmitters levels in the hippocampus and cortex. Behaviorally, after recovery from repeated or chronic ethanol exposure there is impairment in working or episodic memory that can recover with prolonged abstinence. In contrast, after thiamine deficiency there is severe and persistent spatial memory impairments and increased perseverative behavior. The interaction between ethanol and thiamine deficiency does not produce more behavioral or neural pathology, with the exception of reduction of white matter, than long-term thiamine deficiency alone.
Behavioral Neuroscience Program, Department of Psychology, State University of New York at Binghamton, Binghamton, NY 13902, USA.
Ryan P
RP
Vetreno
Joseph M
JM
Hall
Lisa M
LM
Savage
D000437:Alcoholism / Q000150:complications* / Q000473:pathology / Q000523:psychology; D000647:Amnesia / Q000209:etiology* / Q000473:pathology / Q000523:psychology; D000818:Animals; D001921:Brain / Q000473:pathology*; D003704:Dementia / Q000209:etiology* / Q000473:pathology / Q000523:psychology; D004195:Disease Models, Animal; D006801:Humans; D008568:Memory / Q000502:physiology
Behav Neurosci. 1999 Feb;113(1):42-50
10197905
Brain. 2000 Jan;123 ( Pt 1):141-54
10611128
Nature. 2001 Mar 15;410(6826):372-6
11268214
Neuropsychology. 2000 Apr;14(2):178-88
10791858
Alcohol Clin Exp Res. 1997 Sep;21(6):1047-52
9309316
Metab Brain Dis. 2006 Sep;21(2-3):149-61
16724269
J Neurosci Res. 1999 Oct 1;58(1):76-87
10491573
Alcohol Clin Exp Res. 1997 May;21(3):521-9
9161613
Eur J Neurosci. 2003 Apr;17(8):1646-54
12752382
Psychol Med. 1990 Feb;20(1):63-75
2320699
Alcohol Clin Exp Res. 1996 Jun;20(4):752-7
8800395
J Neurochem. 1997 Jun;68(6):2485-92
9166743
J Neurosci. 2002 Feb 1;22(3):1171-6
11826146
Br Med J (Clin Res Ed). 1987 Feb 28;294(6571):534-6
3103762
Brain Res. 1988 Dec;472(4):351-70
3066440
Alcohol Clin Exp Res. 1995 Oct;19(5):1127-32
8561280
Neurobiol Learn Mem. 2008 May;89(4):497-503
18331803
J Neurosci Res. 2000 Feb 1;59(3):353-5
10679770
Behav Brain Res. 1995 Apr;68(1):75-89
7619308
Alcohol Health Res World. 1994;18(3):228-232
31798100
J Neurochem. 1993 Dec;61(6):2175-82
8245970
Alcohol Alcohol. 1985;20(2):201-21
2864938
Neuroscience. 1996 Sep;74(1):155-9
8843084
Behav Brain Res. 2008 Mar 17;188(1):24-31
18061285
Alcohol Clin Exp Res. 1999 Oct;23(10):1587-95
10549989
Neurobiol Learn Mem. 2003 Mar;79(2):177-83
12591225
Br Med Bull. 1994 Jan;50(1):99-114
8149203
Hum Exp Toxicol. 2007 Mar;26(3):251-7
17439928
Adv Exp Med Biol. 1980;126:731-43
7405710
Neuropsychopharmacology. 2005 Feb;30(2):423-32
15562292
Neuroscience. 1999;94(2):431-42
10579206
Front Biosci. 1997 Jun 15;2:d309-16
9206984
Ann N Y Acad Sci. 1999;893:404-11
10672278
J Neurochem. 1968 Jul;15(7):621-31
5675587
Alcohol Clin Exp Res. 2009 Mar;33(3):538-50
19120063
Alcohol. 1990 Nov-Dec;7(6):493-501
2261086
Lancet. 1981 Apr 11;1(8224):824-7
6111682
Eur J Pharmacol. 2010 Mar 10;629(1-3):31-9
20006600
Alcohol Clin Exp Res. 1993 Jun;17(3):525-31
8392817
Brain Res Bull. 2000 Jun;52(3):189-96
10822160
Neurobiol Learn Mem. 2003 Nov;80(3):194-210
14521863
Alcohol Alcohol. 1990;25(2-3):207-16
2198036
Life Sci. 2001 Jul 27;69(10):1181-91
11508350
Neurochem Int. 2002 May;40(6):493-504
11850106
Br J Psychiatry. 1990 May;156:635-44
2099160
Exp Mol Pathol. 1978 Jun;28(3):381-94
648625
Br J Psychiatry. 2008 Nov;193(5):351-3
18978310
Arch Neurol. 1981 Jun;38(6):350-4
7236062
Mol Pharmacol. 2003 Jan;63(1):53-64
12488536
Behav Brain Res. 2004 Jan 5;148(1-2):93-105
14684251
Science. 1999 Sep 17;285(5435):1870-4
10489359
Br J Addict. 1986 Jun;81(3):395-403
3461848
Exp Neurol. 2004 Sep;189(1):173-81
15296847
Brain Res. 1996 Feb 19;709(2):221-8
8833758
Exp Neurol. 1998 Jan;149(1):130-8
9454622
J Neurochem. 1993 Sep;61(3):1155-8
8103080
J Biol Chem. 1997 Aug 1;272(31):19103-6
9235897
J Neurosci. 1990 May;10(5):1664-74
1970604
Alcohol. 1990 Mar-Apr;7(2):145-52
2328088
Yakugaku Zasshi. 2005 Jul;125(7):549-54
15997211
Prog Neurobiol. 1985;25(3):189-287
4089179
Neurobiol Dis. 2008 Feb;29(2):176-85
17936635
Neuroscience. 1993 Sep;56(2):465-71
8247273
Nature. 1988 Mar 31;332(6163):448-50
3352743
Hippocampus. 1997;7(1):78-87
9138671
Cortex. 2003 Sep-Dec;39(4-5):1027-45
14584565
Neuropsychologia. 1982;20(3):233-48
7121792
Learn Mem. 2003 Jul-Aug;10(4):242-6
12888541
J Stud Alcohol. 2000 Jan;61(1):32-7
10627094
J Neurosci Res. 2001 Jan 15;63(2):200-8
11169630
Alcohol Clin Exp Res. 2000 Apr;24(4):465-75
10798582
Alcohol Clin Exp Res. 2004 Nov;28(11):1657-65
15547452
Alcohol Alcohol. 2009 Mar-Apr;44(2):128-35
19155229
Physiol Behav. 2001 Jan;72(1-2):115-21
11239988
J Neurophysiol. 2002 May;87(5):2385-97
11976376
Brain Res. 2000 Dec 1;885(1):62-9
11121530
Alcohol Clin Exp Res. 2006 Nov;30(11):1938-49
17067360
Brain Res. 2007 Mar 30;1139:210-9
17289001
Alcohol. 2006 Feb;38(2):89-97
16839855
Alcohol Clin Exp Res. 1992 Dec;16(6):1052-6
1471759
Neurol Clin. 1993 Feb;11(1):205-18
8441371
Science. 1978 Aug 18;201(4356):646-8
566953
Behav Brain Res. 2001 Mar 15;119(2):167-77
11165332
Alcohol Clin Exp Res. 1999 Oct;23(10):1629-36
10549995
Neurobiol Learn Mem. 2008 Jul;90(1):237-44
18472286
Learn Mem. 2006 Nov-Dec;13(6):699-710
17101872
Alcohol Clin Exp Res. 2000 May;24(5):622-34
10832903
Contemp Neurol Ser. 1971;7:1-206
5162155
Nature. 2006 Feb 2;439(7076):589-93
16341203
Alcohol Clin Exp Res. 1997 Dec;21(9):1553-9
9438512
Int J Addict. 1995 Nov-Dec;30(13-14):1843-69
8751321
Alcohol Alcohol. 2009 Mar-Apr;44(2):115-27
18940959
Behav Brain Res. 1988 Mar;27(3):223-39
2896002
Psychol Bull. 1990 May;107(3):355-66
2190253
Annu Rev Neurosci. 1982;5:241-73
7073209
Neurosci Lett. 1991 Feb 11;123(1):112-4
2062446
Neuropsychopharmacology. 2007 Oct;32(10):2207-16
17299515
Nat Rev Neurosci. 2010 Jul;11(7):459-73
20559335
Neuropsychologia. 1989;27(4):437-60
2733818
Cerebrovasc Brain Metab Rev. 1989 Spring;1(1):2-25
2701368
Curr Opin Pharmacol. 2005 Feb;5(1):73-8
15661629
J Physiol. 1973 Jul;232(2):357-74
4727085
Cortex. 1988 Sep;24(3):367-88
3191722
Synapse. 1994 Jun;17(2):141-8
7916492
Nat Neurosci. 1999 Mar;2(3):260-5
10195219
Behav Brain Res. 1991 Apr 18;43(1):7-28
1677582
J Neuropathol Exp Neurol. 1998 Feb;57(2):101-10
9600202
Neuroscience. 2003;119(3):635-42
12809684
Eur J Neurosci. 2010 Sep;32(5):847-58
20726882
Dement Geriatr Cogn Disord. 2005;20(5):286-91
16166775
Metab Brain Dis. 1996 Mar;11(1):19-37
8815388
Behav Brain Res. 1992 Jun 8;48(2):177-85
1616608
Acta Neurol Scand. 2002 Apr;105(4):276-81
11939939
Br Med J (Clin Res Ed). 1985 Feb 16;290(6467):501-4
3918649
Exp Brain Res. 2003 Jan;148(1):88-94
12478399
Neurology. 2003 Dec 23;61(12):1716-9
14694035
Curr Opin Neurobiol. 2004 Apr;14(2):186-91
15082323
Exp Neurol. 1982 Dec;78(3):574-82
6890906
Brain Res. 2008 Oct 9;1234:116-27
18706897
Synapse. 2003 Jun 15;48(4):189-97
12687638
Alcohol Clin Exp Res. 1997 May;21(3):434-43
9161603
Neuropsychologia. 2007 Mar 14;45(5):905-20
17005214
Neurobiol Learn Mem. 2007 Jan;87(1):123-32
16978888
Lancet. 1986 May 24;1(8491):1184-6
2871423
Alcohol Clin Exp Res. 2004 Apr;28(4):667-75
15100620
Behav Brain Res. 2005 Jul 1;162(1):11-21
15922063
Science. 1980 Aug 8;209(4457):711-3
7394532
Pharmacol Biochem Behav. 1998 Jun;60(2):305-11
9632211
Neuropharmacology. 2004 Mar;46(4):570-9
14975681
Mol Neurodegener. 2009 Dec 21;4:52
20025751
Neurobiol Aging. 1987 Sep-Oct;8(5):429-34
3683723
Eur J Neurosci. 2006 Aug;24(3):645-53
16848797
Alcohol. 1997 Sep-Oct;14(5):445-54
9305459
J Physiol. 1973 Jul;232(2):331-56
4727084
J Clin Exp Neuropsychol. 2008 Jul;30(5):576-87
17852615
Pharmacol Biochem Behav. 2001 Oct-Nov;70(2-3):227-35
11701192
Alcohol Clin Exp Res. 2006 Apr;30(4):680-7
16573587
Alcohol Clin Exp Res. 2005 Jun;29(6):971-82
15976523
Brain Res. 2005 Jun 28;1048(1-2):69-79
15919065
Mol Pharmacol. 2007 Jul;72(1):95-102
17440117
Psychopharmacology (Berl). 1998 Sep;139(1-2):145-53
9768552
Alcohol Clin Exp Res. 2006 Sep;30(9):1538-44
16930216
J Clin Exp Neuropsychol. 1987 Oct;9(5):479-97
2959682
Trends Neurosci. 2003 Feb;26(2):81-9
12536131
J Clin Exp Neuropsychol. 1985 Apr;7(2):181-210
3157699
J Neurobiol. 2004 Sep 15;60(4):490-8
15307153
Alcohol Alcohol. 2009 Mar-Apr;44(2):148-54
19151162
Alcohol. 1997 Jan-Feb;14(1):93-8
9014029
Alcohol Clin Exp Res. 2007 Aug;31(8):1286-96
17561921
Behav Brain Res. 1997 Jan;82(2):133-47
9030395
Neuroscience. 2009 Apr 21;160(1):32-41
19264109
Neuroscience. 1989;33(3):435-62
2636702
J Neurochem. 2002 Dec;83(5):1087-93
12437579
Alcohol Clin Exp Res. 2007 Jan;31(1):156-65
17207114
J Neuropathol Exp Neurol. 1995 Mar;54(2):255-67
7876893
Pharmacol Biochem Behav. 2009 May;92(3):480-7
19463263
Alcohol Clin Exp Res. 1992 Dec;16(6):1078-89
1471762
Pharmacol Ther. 2008 Apr;118(1):36-57
18394710
Addiction. 1993 Feb;88(2):237-47
8220061
Brain. 1979 Dec;102(4):749-83
116710
Neurochem Res. 2005 Dec;30(12):1579-88
16362777
Hippocampus. 2006;16(3):296-304
16411241
Br J Addict. 1986 Oct;81(5):661-9
3466633
J Neurol Sci. 1982 Nov;56(2-3):233-48
7175549
J Neurosci. 1990 Apr;10(4):1372-9
2158533
Behav Neurosci. 1991 Jun;105(3):351-9
1907456
Neuropsychology. 2004 Jul;18(3):589-597
15291737
J Neuropathol Exp Neurol. 1993 Nov;52(6):586-93
8229077
J Neurol Neurosurg Psychiatry. 1982 Sep;45(9):838-40
7131020
Neuropsychiatr Dis Treat. 2006 Sep;2(3):327-39
19412479
J Neurochem. 1989 Apr;52(4):1079-84
2564421
Neuropsychopharmacology. 2009 May;34(6):1427-42
18704091