Levodopa ameliorates learning and memory deficits in a murine model of Alzheimer's disease

被引:91
作者
Ambree, Oliver [1 ]
Richter, Helene [1 ]
Sachser, Norbert [1 ]
Lewejohann, Lars [1 ]
Dere, Ekrem [2 ,3 ]
Silva, Maria Angelica de Souza [2 ,3 ]
Herring, Arne [4 ]
Keyvani, Kathy [4 ]
Paulus, Werner [4 ]
Schaebitz, Wolf-Ruediger [5 ]
机构
[1] Univ Munster, Dept Behav Biol, D-48149 Munster, Germany
[2] Univ Dusseldorf, Inst Physiol Psychol, D-40225 Dusseldorf, Germany
[3] Univ Dusseldorf, Ctr Biol & Med Res, D-40225 Dusseldorf, Germany
[4] Univ Hosp Munster, Inst Neuropathol, D-48149 Munster, Germany
[5] Univ Hosp Munster, Inst Neurol, D-48149 Munster, Germany
关键词
Alzheimer's disease; Dopamine; L-DOPA; Transgenic mice; TgCRND8; Learning and memory; Barnes maze; Spatial learning; Object recognition; Stereotypic behavior; SPATIAL WORKING-MEMORY; DOPAMINE D2 RECEPTORS; APP23 TRANSGENIC MICE; REST-ACTIVITY RHYTHM; PREFRONTAL CORTEX; LOCOMOTOR-ACTIVITY; DELAYED ALTERNATION; OBJECT RECOGNITION; CIRCADIAN-RHYTHMS; D1; RECEPTORS;
D O I
10.1016/j.neurobiolaging.2007.11.010
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
030301 [社会学]; 100201 [内科学];
摘要
Dopamine plays an important role in learning and memory processes. A deficit of this neurotransmitter as it is apparent in Alzheimer's disease (AD) may contribute to cognitive decline, a major symptom of AD patients. The aim of this study was to elucidate whether or not stimulation of the dopaminergic system leads to an improvement of cognitive function and reduction of non-cognitive behavioral alterations in a murine model of AD. Transgenic and wild type male mice of the TgCRND8 line were treated either with the dopamine precursor levodopa or vehicle and tested in two learning tasks, the object-recognition task and the Barnes maze test. Additionally 24 h spontaneous behavior in the home cage was analyzed. In both memory tasks wild type mice performed significantly better than transgenics. However, transgenics treated with levodopa showed a significant object recognition memory and improved acquisition of spatial memory in the Barnes maze compared to vehicle treated transgenics. Concerning spontaneous behavior transgenic mice performed much more stereotypies than wild types. However, there was a trend for reduced stereotypies in the levodopa group in the time the drug was active. Neurochemical analysis revealed elevated levels of dopamine in the neostriata and frontal cortices and reduced levels in the hippocampi of transgenic mice compared to wild types. Thus cognitive deficits and stereotypies may be due to changes in the dopaminergic system as they could be ameliorated by levodopa treatment, that might also have a therapeutic significance for AD. (C) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:1192 / 1204
页数:13
相关论文
共 89 条
[1]
Activity changes and marked stereotypic behavior precede Aβ pathology in TgCRND8 Alzheimer mice [J].
Ambree, Oliver ;
Touma, Chadi ;
Goertz, Nicole ;
Keyvani, Kathy ;
Paulus, Werner ;
Palme, Rupert ;
Sachser, Norbert .
NEUROBIOLOGY OF AGING, 2006, 27 (07) :955-964
[2]
Reduction of amyloid angiopathy and Aβ plaque burden after enriched housing in TgCRND8 mice -: Involevement of multiple pathways [J].
Ambree, Oliver ;
Leimer, Uwe ;
Herring, Arne ;
Goertz, Nicole ;
Sachser, Norbert ;
Heneka, Michael T. ;
Paulus, Werner ;
Keyvani, Kathy .
AMERICAN JOURNAL OF PATHOLOGY, 2006, 169 (02) :544-552
[3]
[Anonymous], 2021, Measuring behaviour: An introductory guide
[4]
MEMORY DEFICITS ASSOCIATED WITH SENESCENCE - NEUROPHYSIOLOGICAL AND BEHAVIORAL-STUDY IN THE RAT [J].
BARNES, CA .
JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY, 1979, 93 (01) :74-104
[5]
COGNITIVE DEFICIT CAUSED BY REGIONAL DEPLETION OF DOPAMINE IN PREFRONTAL CORTEX OF RHESUS-MONKEY [J].
BROZOSKI, TJ ;
BROWN, RM ;
ROSVOLD, HE ;
GOLDMAN, PS .
SCIENCE, 1979, 205 (4409) :929-932
[6]
6-HYDROXYDOPAMINE LESION OF THE RAT PREFRONTAL CORTEX INCREASES LOCOMOTOR-ACTIVITY, IMPAIRS ACQUISITION OF DELAYED ALTERNATION TASKS, BUT DOES NOT AFFECT UNINTERRUPTED TASKS IN THE RADIAL MAZE [J].
BUBSER, M ;
SCHMIDT, WJ .
BEHAVIOURAL BRAIN RESEARCH, 1990, 37 (02) :157-168
[7]
Cabib Simona, 1993, P119
[8]
Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695 [J].
Chishti, MA ;
Yang, DS ;
Janus, C ;
Phinney, AL ;
Horne, P ;
Pearson, J ;
Strome, R ;
Zuker, N ;
Loukides, J ;
French, J ;
Turner, S ;
Lozza, G ;
Grilli, M ;
Kunicki, S ;
Morissette, C ;
Paquette, J ;
Gervais, F ;
Bergeron, C ;
Fraser, PE ;
Carlson, GA ;
St George-Hyslop, P ;
Westaway, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (24) :21562-21570
[9]
Dopaminergic modulation of visual attention and working memory in the rodent prefrontal cortex [J].
Chudasama, Y ;
Robbins, TW .
NEUROPSYCHOPHARMACOLOGY, 2004, 29 (09) :1628-1636
[10]
Cooper SJ., 1990, NEUROBIOLOGY STEREOT, P1