Neuroprotection by rasagiline in thiamine deficient rats

Eliash, Sarah; Dror, Vered; Cohen, Sasson; Rehavi, Moshe

doi:10.1016/j.brainres.2008.11.097

Cited by 22 publications

(12 citation statements)

References 72 publications

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“…The rasagiline dose used (3 mg/kg) has previously been found to be efficacious in models of cerebral ischemia [37], vitamin deficiency [38] and PD [16]. We chose a long-term treatment (4–8 weeks) because we were not only interested in the MAO-B inhibitory activity of rasagiline [39], but also in its potential neuroprotective effects [16], [40].…”

Section: Discussionmentioning

confidence: 99%

“…The rasagiline dose (3 mg/kg/day) can reduce the residual MAO-B activity in the brain from 2% to 0.08% compared to untreated controls [38], [48]. Knowing that MAO-B is expressed in the olfactory bulb [49], [50], it is likely that rasagiline therapy could affect dopamine transmission in the olfactory bulb especially between interneurons and olfactory receptor neurons or mitral/tufted cells in the glomerular layer.…”

Section: Discussionmentioning

confidence: 99%

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Rasagiline Ameliorates Olfactory Deficits in an Alpha-Synuclein Mouse Model of Parkinson's Disease

et al. 2013

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Impaired olfaction is an early pre-motor symptom of Parkinson's disease. The neuropathology underlying olfactory dysfunction in Parkinson's disease is unknown, however α-synuclein accumulation/aggregation and altered neurogenesis might play a role. We characterized olfactory deficits in a transgenic mouse model of Parkinson's disease expressing human wild-type α-synuclein under the control of the mouse α-synuclein promoter. Preliminary clinical observations suggest that rasagiline, a monoamine oxidase-B inhibitor, improves olfaction in Parkinson's disease. We therefore examined whether rasagiline ameliorates olfactory deficits in this Parkinson's disease model and investigated the role of olfactory bulb neurogenesis. α-Synuclein mice were progressively impaired in their ability to detect odors, to discriminate between odors, and exhibited alterations in short-term olfactory memory. Rasagiline treatment rescued odor detection and odor discrimination abilities. However, rasagiline did not affect short-term olfactory memory. Finally, olfactory changes were not coupled to alterations in olfactory bulb neurogenesis. We conclude that rasagiline reverses select olfactory deficits in a transgenic mouse model of Parkinson's disease. The findings correlate with preliminary clinical observations suggesting that rasagiline ameliorates olfactory deficits in Parkinson's disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Rasagiline Ameliorates Olfactory Deficits in an Alpha-Synuclein Mouse Model of Parkinson's Disease

et al. 2013

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“…The doses of MAOIs administered have been well documented in studies examining the therapeutic potential for these drugs (cf. Gal et al, 2005; Saravanan et al, 2006; Eliash et al, 2009). Ethanol (Binge EtOH rats; 25% w/v) or isocalorically-substituted dextrose (Control rats) was formulated in a nutritionally complete diet (Vanilla Ensure Plus ® ) and administered by intragastric gavage.…”

Section: Methodsmentioning

confidence: 99%

Binge ethanol exposure increases the Krüppel-like factor 11-monoamine oxidase (MAO) pathway in rats: Examining the use of MAO inhibitors to prevent ethanol-induced brain injury

et al. 2016

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Binge drinking induces several neurotoxic consequences including oxidative stress and neurodegeneration. Because of these effects, drugs which prevent ethanol-induced damage to the brain may be clinically beneficial. In this study, we investigated the ethanol-mediated KLF11-MAO cell death cascade in the frontal cortex of Sprague–Dawley rats exposed to a modified Majchowicz 4-day binge ethanol model and control rats. Moreover, MAO inhibitors (MAOIs) were investigated for neuroprotective activity against binge ethanol. Binge ethanol-treated rats demonstrated a significant increase in KLF11, both MAO isoforms, protein oxidation and caspase-3, as well as a reduction in BDNF expression in the frontal cortex compared to control rats. MAOIs prevented these binge ethanol-induced changes, suggesting a neuroprotective benefit. Neither binge ethanol nor MAOI treatment significantly affected protein expression levels of the oxidative stress enzymes, SOD2 or catalase. Furthermore, ethanol-induced antinociception was enhanced following exposure to the 4-day ethanol binge. These results demonstrate that the KLF11-MAO pathway is activated by binge ethanol exposure and MAOIs are neuroprotective by preventing the binge ethanol-induced changes associated with this cell death cascade. This study supports KLF11-MAO as a mechanism of ethanol-induced neurotoxicity and cell death that could be targeted with MAOI drug therapy to alleviate alcohol-related brain injury. Further examination of MAOIs to reduce alcohol use disorder-related brain injury could provide pivotal insight to future pharmacotherapeutic opportunities.

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“…1-Deprenyl has been used in Parkinson's disease and has been reported to be of some utility in global ischemia, Tourette syndrome, narcolepsy and possibly Alzheimer's disease (8). One of the results of the interest in the neuroprotective/neurorescue studies on 1-deprenyl has been the development of rasagiline, a structurally related drug (both contain an N-propargyl group) which has now been approved for use in Parkinson's disease in many countries (5,12,13) and been shown to be neuroprotective in a variety of models (5,(14)(15)(16)(17). Indeed, research on the neuroprotective actions of this drug appears to have stimulated research on possible neuroprotective actions of numerous other psychiatric drugs, including antidepressants and antipsychotics.…”

mentioning

confidence: 99%