Evaluation of cholinergic markers in Alzheimer's disease and in a model of cholinergic deficit

被引:65
作者
Gil-Bea, FJ [1 ]
García-Alloza, M [1 ]
Domínguez, J [1 ]
Marcos, B [1 ]
Ramírez, MJ [1 ]
机构
[1] Univ Navarra, Sch Med, CIMA, Ctr Appl Med Res,Dept Pharmacol,Lab Neuropharmaco, Pamplona 31008, Spain
关键词
acetylcholine (ACh); acetyleholinesterase (AChE); cholinacetyltransferase (ChAT); human; cognitive deficit; rat;
D O I
10.1016/j.neulet.2004.10.062
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Cognitive deficits in neuropsychiatric disorders, such as Alzheimer's disease (AD), have been closely related to cholinergic deficits. We have compared different markers of cholinergic function to assess the best biomarker of cognitive deficits associated to cholinergic hypoactivity. In post-mortem frontal cortex from AD patients, acetylcholine (ACh) levels, cholinacetyltransferase (ChAT) and acetylcholinesterase (AChE) activity were all reduced compared to controls. Both ChAT and AChE activity showed a significant correlation with cognitive deficits. In the frontal cortex of rats with a selective cholinergic lesion, all cholinergic parameters measured (ACh levels, ChAT and AChE activities, "in vitro" and "in vivo" basal ACh release) were significantly reduced. AChE activity was associated to ChAT activity, and even more, to "in vivo" and "in vitro" basal ACh release. Quantification of AChE activity is performed by an easy and cheap method and therefore, these results suggest that determination of AChE activity may be used as an effective first step method to evaluate cholinergic deficits. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:37 / 41
页数:5
相关论文
共 38 条
[1]   Does the release of acetylcholine in septal slices originate from intrinsic cholinergic neurons bearing p75NTR receptors?: A study using 192 IgG-saporin lesions in rats [J].
Birthelmer, A ;
Lazaris, A ;
Riegert, C ;
Pereira, PM ;
Koenig, J ;
Jeltsch, H ;
Jackisch, R ;
Cassel, JC .
NEUROSCIENCE, 2003, 122 (04) :1059-1071
[2]   Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease - An in vivo positron emission tomographic study [J].
Bohnen, NI ;
Kaufer, DI ;
Ivanco, LS ;
Lopresti, B ;
Koeppe, RA ;
Davis, JG ;
Mathis, CA ;
Moore, RY ;
DeKosky, ST .
ARCHIVES OF NEUROLOGY, 2003, 60 (12) :1745-1748
[3]   Interactions between aging and cortical cholinergic deafferentation on attention [J].
Burk, JA ;
Herzog, CD ;
Porter, MC ;
Sarter, M .
NEUROBIOLOGY OF AGING, 2002, 23 (03) :467-477
[4]   Lesion-induced transneuronal plasticity of the cholinergic innervation in the adult rat entorhinal cortex [J].
de Lacalle, S ;
Kulkarni, S ;
Wiley, RG .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1998, 10 (03) :1054-1062
[5]   A NEW AND RAPID COLORIMETRIC DETERMINATION OF ACETYLCHOLINESTERASE ACTIVITY [J].
ELLMAN, GL ;
COURTNEY, KD ;
ANDRES, V ;
FEATHERSTONE, RM .
BIOCHEMICAL PHARMACOLOGY, 1961, 7 (02) :88-&
[6]  
Fadel J, 1996, J NEUROSCI, V16, P6592
[7]   Basal forebrain neurons suppress amygdala kindling via cortical but not hippocampal cholinergic projections in rats [J].
Ferencz, I ;
Leanza, G ;
Nanobashvili, A ;
Kokaia, M ;
Lindvall, O .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2000, 12 (06) :2107-2116
[8]   MINI-MENTAL STATE - PRACTICAL METHOD FOR GRADING COGNITIVE STATE OF PATIENTS FOR CLINICIAN [J].
FOLSTEIN, MF ;
FOLSTEIN, SE ;
MCHUGH, PR .
JOURNAL OF PSYCHIATRIC RESEARCH, 1975, 12 (03) :189-198
[9]   RAPID RADIOCHEMICAL METHOD FOR DETERMINATION OF CHOLINE-ACETYLTRANSFERASE [J].
FONNUM, F .
JOURNAL OF NEUROCHEMISTRY, 1975, 24 (02) :407-409
[10]   The cholinergic hypothesis of Alzheimer's disease: a review of progress [J].
Francis, PT ;
Palmer, AM ;
Snape, M ;
Wilcock, GK .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1999, 66 (02) :137-147