Human cholinergic basal forebrain: chemoanatomy and neurologic dysfunction

被引:226
作者
Mufson, EJ
Ginsberg, SD
Ikonomovic, MD
DeKosky, ST
机构
[1] Rush Presbyterian St Lukes Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA
[2] Rush Presbyterian St Lukes Med Ctr, Alzheimers Dis Ctr, Chicago, IL 60612 USA
[3] NYU, Sch Med, Ctr Dementia Res, Nathan Kline Inst,Dept Psychiat, Orangeburg, NY USA
[4] NYU, Sch Med, Dept Physiol & Neurosci, Ctr Dementia Res,Nathan Kline Inst, Orangeburg, NY USA
[5] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA USA
[6] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA
[7] Univ Pittsburgh, Sch Med, Alzheimers Dis Res Ctr, Pittsburgh, PA USA
关键词
human cholinergic basal forebrain; chemoanatomy; neurologic dysfunction;
D O I
10.1016/S0891-0618(03)00068-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The human cholinergic basal forebrain (CBF) is comprised of magnocellular hyperchromic neurons within the septal/diagonal band complex and nucleus basalis (NB) of Meynert. CBF neurons provide the major cholinergic innervation to the hippocampus, amygdala and neocortex. They play a role in cognition and attentional behaviors, and are dysfunctional in Alzheimer's disease (AD). The human CBF displays a continuum of large cells that contain various cholinergic markers, nerve growth factor (NGF) and its cognate receptors, calbindin, glutamate receptors, and the estrogen receptors, ERalpha and ERbeta. Admixed with these cholinergic neuronal phenotypes are smaller interneurons containing the m2 muscarinic acetylcholine receptor (mAChRs), NADPH-diaphorase, GABA, calcium binding proteins and several inhibitory neuropeptides including galanin (GAL), which is over expressed in AD. Studies using human autopsy material indicate an age-related dissociation of calbindin and the glutamate receptor GluR2 within CBF neurons, suggesting that these molecules act synergistically to induce excitotoxic cell death during aging, and possibly during AD. Choline acetyltrasnferease (ChAT) activity and CBF neuron number is preserved in the cholinergic basocortical system and up regulated in the septohippocampal system during prodromal as compared with end stage AD. In contrast, the number of CBF neurons containing NGF receptors is reduced early in the disease process suggesting a phenotypic silence and not a frank loss of neurons. In end stage AD, there is a selective reduction in trkA mRNA but not p75(NTR) in single CBF cells suggesting a neurotrophic defect throughout the progression of AD. These observations indicate the complexity of the chemoanatomy of the human CBF and suggest that multiple factors play different roles in its dysfunction in aging and AD. (C) 2003 Published by Elsevier B.V.
引用
收藏
页码:233 / 242
页数:10
相关论文
共 103 条
[1]  
[Anonymous], 1997, Neurobiol Aging, V18, pS1
[2]  
[Anonymous], 1896, Handbuch der Gewebelehre des Menschen
[3]   NEURONAL LOSS IN DIFFERENT PARTS OF THE NUCLEUS BASALIS IS RELATED TO NEURITIC PLAQUE-FORMATION IN CORTICAL TARGET AREAS IN ALZHEIMERS-DISEASE [J].
ARENDT, T ;
BIGL, V ;
TENNSTEDT, A ;
ARENDT, A .
NEUROSCIENCE, 1985, 14 (01) :1-14
[4]  
Armstrong D.M., 1998, ADV NEURODEGENERATIV, P71
[5]   Metric properties of nurses' ratings of parkinsonian signs with a modified Unified Parkinson's Disease Rating Scale [J].
Bennett, DA ;
Shannon, KM ;
Beckett, LA ;
Goetz, CG ;
Wilson, RS .
NEUROLOGY, 1997, 49 (06) :1580-1587
[6]   Dimensionality of parkinsonian signs in aging and Alzheimer's disease [J].
Bennett, DA ;
Shannon, KM ;
Beckett, LA ;
Wilson, RS .
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, 1999, 54 (04) :M191-M196
[7]   Natural history of mild cognitive impairment in older persons [J].
Bennett, DA ;
Wilson, RS ;
Schneider, JA ;
Evans, DA ;
Beckett, LA ;
Aggarwal, NT ;
Barnes, LL ;
Fox, JH ;
Bach, J .
NEUROLOGY, 2002, 59 (02) :198-205
[8]   INCREASED NUMBER OF NADPH-D-POSITIVE NEURONS WITHIN THE SUBSTANTIA INNOMINATA IN ALZHEIMERS-DISEASE [J].
BENZING, WC ;
MUFSON, EJ .
BRAIN RESEARCH, 1995, 670 (02) :351-355
[9]   GALANIN IMMUNOREACTIVITY WITHIN THE PRIMATE BASAL FOREBRAIN - EVOLUTIONARY CHANGE BETWEEN MONKEYS AND APES [J].
BENZING, WC ;
KORDOWER, JH ;
MUFSON, EJ .
JOURNAL OF COMPARATIVE NEUROLOGY, 1993, 336 (01) :31-39
[10]  
Blurton-Jones MM, 1999, J COMP NEUROL, V405, P529, DOI 10.1002/(SICI)1096-9861(19990322)405:4<529::AID-CNE6>3.0.CO