Symptomatic effect of donepezil, rivastigmine, galantamine and memantine on cognitive deficits in the APP23 model

Dam, Debby Van; Abramowski, Dorothée; Staufenbiel, Matthias; Deyn, Peter Paul De

doi:10.1007/s00213-004-2132-z

Cited by 122 publications

(70 citation statements)

References 82 publications

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“…We were surprised to find no effect of memantine on contextual memory in a fear conditioning paradigm given that we used doses similar to those previously been reported to have beneficial behavioral effects in other transgenic mouse models of AD (Minkeviciene et al, 2004;Van Dam et al, 2005;Van Dam and De Deyn, 2006). The behavior deficits we observed in Tg + mice replicated earlier findings using Tg2576 mice (Hsiao et al, 1996;Corcoran et al, 2002;Arendash et al, 2004;Barnes and Good, 2005;Dong et al, 2005) and thus imply validity of the behavioral test employed here.…”

Section: Discussionsupporting

confidence: 71%

“…Minkeviciene et al (2004) reported improved acquisition in water maze using APP/PS1 transgenic mice treated with 30 mg/kg memantine in drinking water for 3 weeks, whereas no effect was observed on retention. Conversely, Van Dam et al (2005) reported beneficial effects of a much lower dose (2.0 mg/kg) of memantine while higher doses (10 mg/kg) demonstrated detrimental effects in the water maze. As compared with these studies, we found that a 5 mg/kg dose was associated with better performance than a 10 mg/kg dose, even though we did not detect a significant overall effect of memantine in Tg2576 mice.…”

Section: Discussionmentioning

confidence: 96%

“…The behavior deficits we observed in Tg + mice replicated earlier findings using Tg2576 mice (Hsiao et al, 1996;Corcoran et al, 2002;Arendash et al, 2004;Barnes and Good, 2005;Dong et al, 2005) and thus imply validity of the behavioral test employed here. At present, the effects of memantine on behavior in transgenic mouse models of AD (Minkeviciene et al, 2004;Van Dam et al, 2005;Van Dam and De Deyn, 2006), as well as other models (Barnes et al, 1996;MiguelHidalgo et al, 2002;Lang et al, 2004;Woodruff-Pak et al, 2007; for review see Yuede et al, 2007) are inconsistent. Minkeviciene et al (2004) reported improved acquisition in water maze using APP/PS1 transgenic mice treated with 30 mg/kg memantine in drinking water for 3 weeks, whereas no effect was observed on retention.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Memantine on Neuronal Structure and Conditioned Fear in the Tg2576 Mouse Model of Alzheimer's Disease

Dong

Yuede

Coughlan

et al. 2008

Neuropsychopharmacol

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Memantine, an uncompetitive NMDA receptor antagonist used for the treatment of Alzheimer's disease (AD), has been hypothesized to have neuroprotective properties. However, the similarity of its mechanism of action to other NMDA receptor antagonists has led to concerns that it may also have neurotoxic effects. To assess both the neuroprotective and neurotoxic potential of memantine in a mouse model of AD (Tg2576 mice), we used quantitative light and electron microscopy to investigate the effects of long-term (6 months) administration of memantine (5, 10 and 20 mg/kg) on plaque deposition and neuronal morphology in the hippocampus and overlying cortex. A fear-conditioning paradigm was used to evaluate the behavioral consequences of any observed changes in structure. Administration of the two higher doses of memantine (10 and 20 mg/kg) was associated with a significant decrease in b-amyloid (Ab) plaque deposition, increases in synaptic density and the appearance of degenerating axons; the latter two effects were independent of genotype. Administration of the lowest dose of memantine (5 mg/kg) was associated with a significant decrease in Ab plaque deposition and a significant increase in synaptic density, but not a significant increase in degenerating axons. However, memantine did not significantly improve behavioral deficits associated with genotype in a fear-conditioning paradigm at any dose. These results suggest that chronic memantine administration may have both neuroprotective and neurotoxic effects in a mouse model of AD.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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Effects of Memantine on Neuronal Structure and Conditioned Fear in the Tg2576 Mouse Model of Alzheimer's Disease

Dong

Yuede

Coughlan

et al. 2008

Neuropsychopharmacol

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“…Animals were injected intraperitoneally with 0.5 mg/kg rivastigmine (total volume, 5 ml/kg) 60 min before the start of anxiety behavioral tests. This optimal dose of rivastigmine was chosen based on previously published microdialysis studies (Van Dam et al, 2005;Cerbai et al, 2007). Both PLC-␤4 ϩ/ϩ (WT) and PLC-␤4 Ϫ/Ϫ (KO) mice were randomly assigned to one of the following three treatment groups: (1) WT-sham (wild-type mice with intraperitoneal injection of saline; n ϭ 10); (2) KO-sham (PLC-␤4 Ϫ/Ϫ mice with intraperitoneal injection of saline; n ϭ 10); and (3) KO-rivastigmine (PLC-␤4 Ϫ/Ϫ mice with intraperitoneal injection of rivastigmine; n ϭ 10).…”

Section: Plc-␤4-null (Plc-␤4mentioning

confidence: 99%

“…To further confirm the interrelationship between cholinergic theta rhythms and anxiety behavior, we designed an experiment to determine whether increasing cholinergic transmission in PLC-␤4 Ϫ/Ϫ mice could rescue the attenuated amplitude of cholinergic theta rhythms, and thereby normalize the attendant anxiety behavior. To this end, we administered the cholinergicenhancing drug, rivastigmine, an acetylcholinesterase inhibitor known to increase the cholinergic transmission in the septohippocampal pathway (Wu et al, 2003b;Van Dam et al, 2005;Cerbai et al, 2007).…”

Section: Rescue Of the Plc-␤4mentioning

confidence: 99%

Phospholipase C β4 in the Medial Septum Controls Cholinergic Theta Oscillations and Anxiety Behaviors

Shin

Gangadharan²,

Kim³

et al. 2009

J. Neurosci.

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Anxiety is among the most prevalent and costly diseases of the CNS, but its underlying mechanisms are not fully understood. Although attenuated theta rhythms have been observed in human subjects with increased anxiety, no study has been done on the possible physiological link between these two manifestations. We found that the mutant mouse for phospholipase C ␤4 (PLC-␤4 Ϫ/Ϫ ) showed attenuated theta rhythm and increased anxiety, presenting the first animal model for the human condition. PLC-␤4 is abundantly expressed in the medial septum, a region implicated in anxiety behavior. RNA interference-mediated PLC-␤4 knockdown in the medial septum produced a phenotype similar to that of PLC-␤4 Ϫ/Ϫ mice. Furthermore, increasing cholinergic signaling by administering an acetylcholinesterase inhibitor cured the anomalies in both cholinergic theta rhythm and anxiety behavior observed in PLC-␤4 Ϫ/Ϫ mice. These findings suggest that (1) PLC-␤4 in the medial septum is involved in controlling cholinergic theta oscillation and (2) cholinergic theta rhythm plays a critical role in suppressing anxiety. We propose that defining the cholinergic theta rhythm profile may provide guidance in subtyping anxiety disorders in humans for more effective diagnosis and treatments.

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Cognition

Hudkins¹,

Marino²,

Williams³

2010

Burger's Medicinal Chemistry and Drug Discovery

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Therapeutic approaches to ameliorating cognitive dysfunction can be viewed as ends of a continuum, from the prophylactic enhancement of cognitive function to the restoration of function and/or arrest of the decline of cognition that occurs in the aging or traumatized brain. Research in the field of cognition is a high priority as the elderly population increases, with a great need to discover and develop drugs to treat age‐related cognitive disorders, including dementias, as well as cognitive impairments associated with neuropsychiatric disorders, such as schizophrenia. Aspects of cognitive dysfunction also occur in association with several CNS disorders, including Parkinson's disease, AIDS‐associated dementia, stroke, stress, sleep deprivation, depression, and anxiety, as well as with recreational and prescription drug usage and surgical procedures. Cognition is a complex set of processes, including attention, perception, emotion, learning and memory, action, and problem solving. Drugs currently approved for use in the treatment of neurodegenerative disorders such as AD include the cholinesterase inhibitors donepezil, rivastigmine, and galantamine, and memantine, a partial agonist at glutamate receptors. Since none of these drugs works especially well in treating the symptoms of AD, a variety of new chemical entities are currently being explored to identify new cognitive enhancers. This chapter covers the biological aspects of cognition and memory and the medicinal chemistry approaches to targeting cognitive deficits in disease.

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Symptomatic effect of donepezil, rivastigmine, galantamine and memantine on cognitive deficits in the APP23 model

Cited by 122 publications

References 82 publications

Effects of Memantine on Neuronal Structure and Conditioned Fear in the Tg2576 Mouse Model of Alzheimer's Disease

Effects of Memantine on Neuronal Structure and Conditioned Fear in the Tg2576 Mouse Model of Alzheimer's Disease

Phospholipase C β4 in the Medial Septum Controls Cholinergic Theta Oscillations and Anxiety Behaviors

Cognition

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