Cholinesterase Inhibitors Improve Both Memory and Complex Learning in Aged Beagle Dogs

Araujo, Joseph A.; Greig, Nigel H.; Ingram, Donald K.; Sandin, Johan; Rivera, Christina de; Milgram, Norton W.

doi:10.3233/jad-2011-110005

Cited by 40 publications

(36 citation statements)

References 93 publications

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“…The cloning, sequencing and expression of APP isoforms and the enzymes related to their processing also parallel the findings in human brain [100]. The dogs also show cholinergic hypofunction similar to that seen in human AD brain, suggesting that this model could be used for therapeutic screening as well as understanding the links between cholinergic functioning, Aβ pathology, and cognitive decline [101]. …”

Section: The Canine Model For the Study And Treatment Of Oxidativementioning

confidence: 87%

Antioxidants in Down syndrome

Lott

2012

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Individuals with Down syndrome (DS) have high levels of oxidative stress throughout the lifespan. Mouse models of DS share some structural and functional abnormalities that parallel findings seen in the human phenotype. Several of the mouse models show evidence of cellular oxidative stress and have provided a platform for antioxidant intervention. Genes that are overexpressed on chromosome 21 are associated with oxidative stress and neuronal apoptosis. The lack of balance in the metabolism of free radicals generated during processes related to oxidative stress may have a direct role in producing the neuropathology of DS including the tendency to Alzheimer disease (AD). Mitochondria are often a target for oxidative stress and are considered to be a trigger for the onset of the AD process in DS. Biomarkers for oxidative stress have been described in DS and in AD in the general population. However, intervention trials using standard antioxidant supplements or diets have failed to produce uniform therapeutic effect. This chapter will examine the biological role of oxidative stress in DS and its relationship to abnormalities in both development and aging within the disorder. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.

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Section: The Canine Model For the Study And Treatment Of Oxidativementioning

confidence: 87%

Antioxidants in Down syndrome

Lott

2012

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…The higher anticholinesterase activity of xanthohumol in comparison to isoxanthohumol was probably due to the differences in the structures of the two prenylated chalcones (lack of the central heterocyclic ring in xanthohumol). Very efficient inhibitors, such as donepezil or phenserine [Araujo et al, 2011], contain a short aliphatic fragment between the phenol rings. The increased bending of the molecule could positively influence the anticholinesterase activity of such compounds.…”

Section: Resultsmentioning

confidence: 99%

Anticholinesterase Activities of Selected Polyphenols – a Short Report

Szwajgier¹

2014

Pol. J. Food Nutr. Sci.

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In this work, anticholinesterase activities of 24 polyphenolic compounds were tested using the modified Ellman's spectrophotometric method. The most efficient acetyl-and butyrylcholinesterase inhibitors were anthocyanins (pelargonidin, delphinidin and cyanidin), flavones (apigenin and luteolin), flavonols (quercetin, kaempferol and myricetin), as well as dihydrochalcone phloridzin and prenylated chalcone xanthohumol. It was established that all the tested compounds were within a narrow molecular weight range of 254.24-354.40 g/mol, which probably was not discriminative for their inhibitory activity. Among all the classes of polyphenolic compounds, the lowest activities were exerted by flavan-3-ols. The inhibitory activity of the tested polyphenols was decreased by the presence of a 3-hydroxyl group. A simultaneous substitution of a carbonyl group at position 4 and a hydroxyl group at position 3 or a lack of both of these substitutions had no effect on the activity of the investigated compounds. The number and position of other hydroxyl groups in the tested molecules played a minor role in this context. Aglycons were more effective cholinesterase inhibitors than their corresponding glycosylated forms. Overall, the results show that phenolic acids can play a role in neuroprotection. However, further in vitro and in vivo studies involving a larger number of polyphenolic compounds simultaneously with well-known cholinesterase inhibitors should be performed in the nearest future to confirm these findings. Unauthenticated Download Date | 5/8/18 4:25 AM

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“…Previous work with these drugs has suggested possible dosage ranges for behavioral experiments [8,9,10,11,12], but the optimal dosage range for each drug is still unknown. Indeed, several previous studies with nonselective cholinergic drugs have observed a limited range of beneficial efficacy for improving memory, a range that varies across individuals, or a strong link between performance during control conditions and the degree of cognitive benefit from cholinergic enhancement [13,14,15,16]. Accordingly, identifying M 1 - or M 4 -selective drugs that improve memory performance in a general experimental population will likely depend on the use of different doses and taking subject differences in baseline memory performance into account.…”

Section: Introductionmentioning

confidence: 99%

Effects of Selective Activation of M<sub>1</sub> and M<sub>4</sub> Muscarinic Receptors on Object Recognition Memory Performance in Rats

Galloway¹,

Lebois

Shagarabi³

et al. 2014

Pharmacology

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Acetylcholine signaling through muscarinic receptors has been shown to benefit memory performance in some conditions, but pan-muscarinic activation also frequently leads to peripheral side effects. Drug therapies that selectively target M₁ or M₄ muscarinic receptors could potentially improve memory while minimizing side effects mediated by the other muscarinic receptor subtypes. The ability of three recently developed drugs that selectively activate M₁ or M₄ receptors to improve recognition memory was tested by giving Long-Evans rats subcutaneous injections of three different doses of the M₁ agonist VU0364572, the M₁ positive allosteric modulator BQCA or the M₄ positive allosteric modulator VU0152100 before performing an object recognition memory task. VU0364572 at 0.1 mg/kg, BQCA at 1.0 mg/kg and VU0152100 at 3.0 and 30.0 mg/kg improved the memory performance of rats that performed poorly at baseline, yet the improvements in memory performance were the most statistically robust for VU0152100 at 3.0 mg/kg. The results suggested that selective M₁ and M₄ receptor activation each improved memory but that the likelihood of obtaining behavioral efficacy at a given dose might vary between subjects even in healthy groups depending on baseline performance. These results also highlighted the potential of drug therapies that selectively target M₁ or M₄ receptors to improve memory performance in individuals with impaired memory.

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Cholinesterase Inhibitors Improve Both Memory and Complex Learning in Aged Beagle Dogs

Cited by 40 publications

References 93 publications

Antioxidants in Down syndrome

Antioxidants in Down syndrome

Anticholinesterase Activities of Selected Polyphenols – a Short Report

Effects of Selective Activation of M<sub>1</sub> and M<sub>4</sub> Muscarinic Receptors on Object Recognition Memory Performance in Rats

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