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

Ambrée, Oliver; Richter, S. Helene; Sachser, Norbert; Lewejohann, Lars; Dere, Ekrem; Silva, Maria Angélica de Souza; Herring, Arne; Keyvani, Kathy; Paulus, Werner; Schäbitz, Wolf‐Rüdiger

doi:10.1016/j.neurobiolaging.2007.11.010

Cited by 88 publications

(59 citation statements)

References 83 publications

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“…In the light of dramatic effect on striatal dopamine innervation by CDNF microinjection [11] and evidence that D1/D5 dopamine receptor stimulation enhances spatial memory [21] augmented hippocampal dopamine neurotransmission appears the most likely mechanism. There is also evidence that L-DOPA treatment selectively ameliorates spatial learning in APP transgenic mice [22]. We could confirm the decreased levels of TH in the hippocampus as reported earlier in the same APPswe/PS1dE9 mouse [23] and further showed that this applies also to D1-receptors.…”

Section: Discussionsupporting

confidence: 89%

Cerebral dopamine neurotrophic factor improves long-term memory in APP/PS1 transgenic mice modeling Alzheimer's disease as well as in wild-type mice

Kemppainen

Lindholm

Galli

et al. 2015

Behavioural Brain Research

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Section: Discussionsupporting

confidence: 89%

Cerebral dopamine neurotrophic factor improves long-term memory in APP/PS1 transgenic mice modeling Alzheimer's disease as well as in wild-type mice

Kemppainen

Lindholm

Galli

et al. 2015

Behavioural Brain Research

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“…In this regard, it has been reported that mice carrying a double mutated form of the human APP, which rapidly develops amyloid plaques at 3 mo of age, have a decrease in DA content in the prefrontal cortex, hippocampus, and neostriatum. The cognitive deficits related with this mice model can be ameliorated by systemic and repeated administration of L-DOPA (Ambree et al 2009). It has also been reported that, as we have seen in this study, novel stimulation induces significant DA release (Girault and Greengard 2004;Ungless 2004;De Leonibus et al 2006;Schultz 2007;Guzmán-Ramos et al 2010).…”

Section: Discussionmentioning

confidence: 92%

“…Repeated i.p. levodopa injections administered to transgenic mice carrying human APPSwe + Ind (TgCRND8) enhance long-term ORM as well as spatial memory task in a Barnes maze (Ambree et al 2009). Similarly, systemic administration of the dopamine receptor agonist apomorphine improves water maze performance of 3xTg-AD mice and decreases intraneuronal levels of Ab in the hippocampus (Himeno et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Several brain structures are involved in the discrimination between novel and familiar stimuli (Zhu et al 1997;Brown and Aggleton 2001;Bermudez-Rattoni 2004;Barker et al 2007); among these, the activity of the insular cortex has been related to memory for several types of stimuli, including odor (Bermudez-Rattoni et al 1988), taste , spatial context (Bermudez-Rattoni et al 1991), and objects (Bermudez-Rattoni et al 2005;Balderas et al 2008). Transgenic mice carrying a double mutation of the amyloid precursor protein (APP) have impaired performance in ORM, as well as decreased levels of DA in the hippocampus and prefrontal cortex (Ambree et al 2009). There is also evidence that DA is involved in ORM formation in normal animals.…”

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confidence: 99%

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Restoration of dopamine release deficits during object recognition memory acquisition attenuates cognitive impairment in a triple transgenic mice model of Alzheimer's disease

et al. 2012

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Previous findings indicate that the acquisition and consolidation of recognition memory involves dopaminergic activity. Although dopamine deregulation has been observed in Alzheimer's disease (AD) patients, the dysfunction of this neurotransmitter has not been investigated in animal models of AD. The aim of this study was to assess, by in vivo microdialysis, cortical and hippocampal dopamine, norepinephrine, and glutamate release during the acquisition of object recognition memory (ORM) in 5-and 10-mo-old triple-transgenic Alzheimer's disease mice (3xTg-AD) and to relate the extracellular changes to 24-h memory performance. Five-and 10-mo-old wild-type mice and 5-mo-old 3xTg-AD showed significant cortical but not hippocampal dopamine increase during object exploration. On a 24-h ORM test, these three groups displayed significant ORM. In contrast, 10-mo-old 3xTg-AD mice showed impaired dopamine release in the insular cortex during ORM acquisition, as well as significant impairment in ORM. In addition, cortical administration of a dopamine reuptake blocker produced an increase of dopamine levels in the 10-mo-old 3xTg-AD mice and attenuated the memory impairment. These data suggest that activation of the dopaminergic system in the insular cortex is involved in object recognition memory, and that dysfunction of this system contributes to the age-related decline in cognitive functioning of the 3xTg-AD mice.Alzheimer's disease (AD) is an age-related and progressive degenerative disorder generally characterized by two neuropathological features: deposits of amyloid-beta (Ab) peptides and neurofibrillary tangles, formed by the hyperphosphorylated microtubulebinding protein tau (Selkoe 2001). These neuropathological features are generally prominent in learning and memory-related brain regions, including the hippocampus, amygdala, and neocortex (Braak and Braak 1991;Nicholson et al. 2010). Because these pathologies are related to synaptic dysfunction leading to neurotransmitter deregulation including acetylcholine deficiency (Davis et al. 1999), several pharmacological therapies for AD focus on the restoration or modulation of cholinergic neurotransmission by acetylcholinesterase inhibitors and muscarinic agonists (Caccamo et al. 2009;Galluzzi et al. 2010). However, there is also evidence that these treatments may increase extracellular levels of dopamine (DA) (Shearman et al. 2006;Preda et al. 2008), suggesting that DA increase may contribute to the therapeutic effect. The possibility that the dopaminergic system may be involved in AD is suggested by evidence of decreased DA levels assessed in post-mortem brain tissue of AD patients (Winblad et al. 1985;Nazarali and Reynolds 1992;Storga et al. 1996), as well as changes in DA receptor distribution and density in several brain structures of the temporal lobe (Joyce et al. 1993(Joyce et al. , 1998Kemppainen et al. 2003;Kumar and Patel 2007).Transgenic models of AD are widely used to study the role of Ab accumulation and tau tangles in the cognitive alterations characteristi...

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“…This is exemplified with deficits in NOR [32,[51][52][53][54][55], T-maze [50,[56][57][58][59][60] and Barnes maze [53,[61][62][63] in transgenic AD mice, which express mutant forms of amyloid precursor protein, presenilin and/or mapt (tau) genes [64,65]. It should be noticed, however, that the time course of cognitive decline is specific for each model [66].…”

Section: Discussionmentioning

confidence: 99%

Memory formation and retention are affected in adult miR-132/212 knockout mice

Hernandez-Rapp

Smith

Filali³

et al. 2015

Behavioural Brain Research

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

Cited by 88 publications

References 83 publications

Cerebral dopamine neurotrophic factor improves long-term memory in APP/PS1 transgenic mice modeling Alzheimer's disease as well as in wild-type mice

Cerebral dopamine neurotrophic factor improves long-term memory in APP/PS1 transgenic mice modeling Alzheimer's disease as well as in wild-type mice

Restoration of dopamine release deficits during object recognition memory acquisition attenuates cognitive impairment in a triple transgenic mice model of Alzheimer's disease

Memory formation and retention are affected in adult miR-132/212 knockout mice

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