Dimebon improves learning in animals with experimental Alzheimer's disease

Lermontova, N. N.; Lukoyanov, Nikolay; Serkova, T. P.; Lukoyanova, Elena A.; Бачурин, С. О.

doi:10.1007/bf02434871

Cited by 59 publications

(40 citation statements)

References 7 publications

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“…In rats treated with the neurotoxin AF64A, which selectively lesions cholinergic neurons and impairs active avoidance, 10-day administration of dimebon reversed these deficits (1 mg/kg/day, i.p. ; Lermontova et al, 2000). Similar results were obtained in the Morris water maze in rats subjected to intracerebroventricular administration of AF64: chronic administration of dimebon at the dose of 0.05 mg/kg rescued spatial learning, which was disrupted by chemical lesion of the dorsal hippocampus (Bachurin et al, 2006).…”

Section: Introductionmentioning

confidence: 52%

Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice

Vignisse

Steinbusch

Bolkunov

et al. 2011

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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a b s t r a c t a r t i c l e i n f oPre-clinical and clinical studies on dimebon (dimebolin or latrepirdine) have demonstrated its use as a cognitive enhancer. Here, we show that dimebon administered to 3-month-old C57BL6N mice 15 min prior to training in both appetitive and inhibitory learning tasks via repeated (0.1 mg/kg) and acute (0.5 mg/kg) i.p. injections, respectively, increases memory scores. Acute treatment with dimebon was found to enhance inhibitory learning, as also shown in the step-down avoidance paradigm in 7-month-old mice. Bolus administration of dimebon did not affect the animals' locomotion, exploration or anxiety-like behaviour, with the exception of exploratory behaviour in older mice in the novel cage test. In a model of appetitive learning, a spatial version of the Y-maze, dimebon increased the rate of correct choices and decreased the latency of accessing a water reward after water deprivation, and increased the duration of drinking behaviour during training/testing procedures. Repeated treatment with dimebon did not alter the behaviours in other tests or water consumption. Acute treatment of water-deprived and non-water-deprived mice with dimebon also did not affect their water intake. Our data suggest that dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory tasks in mice.

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Section: Introductionmentioning

confidence: 52%

Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice

Vignisse

Steinbusch

Bolkunov

et al. 2011

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…In view of the recent demonstration of its efficacy in a phase II clinical trial, dimebon may well become a new drug for the treatment of AD and other neurodegenerative diseases. Although there have been some reports suggesting that dimebon may act as a neuroprotective agent and prevent mitochondrial pore transition in experimental models of AD [36] and Huntington's disease [30], its precise mode of action remains unknown. The present study suggests that dimebon may act by reducing the production or accumulation of abnormal protein aggregates.…”

Section: Discussionmentioning

confidence: 99%

Methylene blue and dimebon inhibit aggregation of TDP‐43 in cellular models

et al. 2009

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a b s t r a c tAmyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) are major neurodegenerative diseases with TDP-43 pathology. Here we investigated the effects of methylene blue (MB) and dimebon, two compounds that have been reported to be beneficial in phase II clinical trials of Alzheimer's disease (AD), on the formation of TDP-43 aggregates in SH-SY5Y cells. Following treatment with 0.05 lM MB or 5 lM dimebon, the number of TDP-43 aggregates was reduced by 50% and 45%, respectively. The combined use of MB and dimebon resulted in a 80% reduction in the number. These findings were confirmed by immunoblot analysis. The results indicate that MB and dimebon may be useful for the treatment of ALS, FTLD-U and other TDP-43 proteinopathies.

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“…The dose of imipramine was based on previous studies with CD1 mice, in which its chronic administration at 7 mg/kg/day effectively reduced the stress-induced decrease in sucrose intake and preference, floating behavior and alteration of hippocampal gene expression typical of the subgroup of mice susceptible to anhedonia ). The dosage of dimebon was determined according to its efficacy in clinic (Doody et al, 2008), as well as in improving learning in the Morris water maze paradigm in aged Wistar rats treated with 1 mg/kg/day of this compound for 3 weeks (Lermontova et al, 2000) and in C57BL6N mice in a step-down avoidance and conditioned fear extinction tests (Vignisse et al, submitted for publication). Drugs were delivered in the drinking water (see Section 2.4).…”

Section: Experiments 4: Effects Of Imipramine and Dimebon On Hedonic Amentioning

confidence: 99%

Anhedonic-like traits and lack of affective deficits in 18-month-old C57BL/6 mice: Implications for modeling elderly depression

Malatyńska

Steinbusch

Redkozubova

et al. 2012

Experimental Gerontology

103

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The prevalence of depression increases with aging. We hypothesized that like humans, old animals exhibit anhedonic-like behavior, along with signs of behavioral despair. In rodents, anhedonia, a reduced sensitivity to reward, which is listed as a core feature of major depression in the DSM-IVR, can be measured by a decrease in intake of and preference for sweet solutions. Here, sucrose intake, forced swimming, immobility in the modified tail suspension test, novelty exploration, grooming, anxiety and locomotor activity were compared in naïve 3-and 18-month-old male C57BL/6 mice. The absolute amounts and the ratio of consumed 1% sucrose solution to water intake was significantly smaller in 18-month-old mice than in 3-month-old mice. The consumption of 5%-sucrose solution requiring high levels of drinking effort, novelty exploration in two setups and grooming behavior in the splash test were reduced in older animals. Analysis of other behaviors suggested that the above-mentioned signs of anhedonic-like traits were unlikely to be attributable to the potential effect of aging on metabolic needs for water, taste perception, motor capabilities or the induction of essential anxiety and neophobia. A 4-week treatment with the antidepressant imipramine (7 mg/kg/day) or dimebon, a compound with suggested neuroprotective proneurogenic properties (1 mg/kg/day) restored sucrose intake and preference in 18-month-old mice. Meanwhile, young and old mice showed no differences in the parameters of behavioral despair evaluated in the forced swim and modified tail suspension tests. Thus, the behavioral profile of aged mice parallels that of humans with elderly depression, in whom the symptoms of hedonic deficits typically outweigh affective disturbances. The assessment of anhedonic-like traits with the sucrose preference test in 18-month-old mice will be useful in preclinical studies of elderly depression.

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Dimebon improves learning in animals with experimental Alzheimer's disease

Cited by 59 publications

References 7 publications

Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice

Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice

Methylene blue and dimebon inhibit aggregation of TDP‐43 in cellular models

Anhedonic-like traits and lack of affective deficits in 18-month-old C57BL/6 mice: Implications for modeling elderly depression

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