Neuroprotection by rasagiline in thiamine deficient rats

Sarah Eliash, Vered Dror, Sasson Cohen, Moshe Rehavi

Research output: Contribution to journalArticlepeer-review

Abstract

Thiamine deficiency (TD) in rats is a model of chronic impairment of oxidative metabolism leading to neuronal loss. TD rats exhibit neuropathological, behavioral and cognitive abnormalities. The aim of this study was to use this syndrome to assess the neuroprotective potential of drugs in a whole animal model. TD was produced in rats using the following protocol: thiamine deficient diet, daily injections of the central thiamine antagonist, pyrithiamine (0.5 mg/kg), and the test drugs, the selective monoamine oxidase (MAO) B inhibitors, rasagiline (1 or 3 mg/kg/day) and selegiline (2.4 or 8 mg/kg/day). Normal rats and untreated TD rats served as controls. Upon the appearance of neurological symptoms, the TD protocol was suspended, rats were transferred to a regular diet, pyrithiamine and test drug injections were terminated and rats were injected with 3 daily doses of thiamine (100 mg/kg). Neuroprotective potential was assessed by: general behavioral observations, cognitive testing using the Morris water maze and histopathological examination of the brains. Rasagiline but not selegiline significantly delayed the onset and severity of the neurological symptoms of TD. In the Morris water maze, TD-untreated rats displayed severe cognitive impairment while rasagiline-treated rats were similar to control rats and significantly different from TD-untreated rats. The effects were dose related. Selegiline treatment had no significant protective effect. TD-untreated brains displayed extensive gliotic and necrotic lesions mainly in the thalamus and posterior collicular nucleus, which were significantly reduced in the rasagiline-treated TD rats. These findings demonstrate significant neuroprotection by rasagiline with possible implications for clinical neurodegenerative disorders.

Original languageEnglish
Pages (from-to)138-148
Number of pages11
JournalBrain Research
Volume1256
DOIs
StatePublished - 23 Feb 2009

Keywords

  • MAO-B inhibitors
  • Neuroprotection
  • Pyrithiamine
  • Rasagiline
  • Selegiline
  • Thiamine deficiency (TD)

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