Neurotoxicity Research

, Volume 35, Issue 3, pp 724–738 | Cite as

Postnatal Administration of Homocysteine Induces Cerebellar Damage in Rats: Protective Effect of Folic Acid

  • Hakimeh Koohpeyma
  • Iran GoudarziEmail author
  • Mahmoud Elahdadi Salmani
  • Taghi Lashkarbolouki
  • Mohammad Shabani
Original Article


A widely held view suggests that homocysteine (Hcy) can contribute to neurodegeneration through promotion of oxidative stress. There is evidence that homocysteine is toxic to cerebellar Purkinje neurons in vitro; however, in vivo action of Hcy on Purkinje cell has not been investigated so far. Thus, this study was designed to evaluate the Hcy effects on neonatal rat cerebellum and cerebellar oxidative stress. We also evaluated the folic acid effects on biochemical alterations elicited by hyperhomocysteinemia (hHcy) in the cerebellum. Group I received normal saline, group II received Hcy subcutaneously twice a day at 8-h intervals (0.3–0.6 μmol/g body weight), group III received Hcy + folic acid (0.011 μmol/g body weight), and group IV received folic acid on postnatal day (PD) 4 until 25. On day 25, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in the cerebellum and motor cortex were assayed. Malondialdehyde (MDA) levels were also evaluated as a marker of lipid peroxidation. Rotarod and locomotor activity tests were performed in PD 25–27. Our results indicated that administration of Hcy increased plasma, cortical, and cerebellar total Hcy levels; reduced GPx activity; and induced lipid peroxidation in the cerebellum. Hcy impaired performance on the rotarod in rats. However, treatment with folic acid significantly attenuated motor coordination impairment, GPx activity reduction, the lipid peroxidation process, and significantly reduced plasma total Hcy levels. Histological analysis indicated that Hcy could decrease Purkinje cell count and folic acid prevented this toxic effect. We conclude that Hcy can induce neurotoxicity and folic acid has neuroprotective effects against cerebellar Hcy toxicity.


Homocysteine Folic acid Purkinje cell Oxidative stress Rat 


Compliance with ethical standards

The experimental protocol was approved by the Research and Ethics Committee of Damghan University.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of BiologyDamghan UniversityDamghanIran
  2. 2.Neuroscience Research CenterKerman University of Medical SciencesKermanIran

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