PMID- 30443710 OWN - NLM STAT- MEDLINE DCOM- 20190515 LR - 20200225 IS - 1476-3524 (Electronic) IS - 1029-8428 (Linking) VI - 35 IP - 3 DP - 2019 Apr TI - Postnatal Administration of Homocysteine Induces Cerebellar Damage in Rats: Protective Effect of Folic Acid. PG - 724-738 LID - 10.1007/s12640-018-9979-y [doi] AB - 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 mumol/g body weight), group III received Hcy + folic acid (0.011 mumol/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. FAU - Koohpeyma, Hakimeh AU - Koohpeyma H AD - School of Biology, Damghan University, Damghan, 3671641167, Iran. FAU - Goudarzi, Iran AU - Goudarzi I AUID- ORCID: 0000-0002-6665-3202 AD - School of Biology, Damghan University, Damghan, 3671641167, Iran. irangoudarzi@du.ac.ir. FAU - Elahdadi Salmani, Mahmoud AU - Elahdadi Salmani M AD - School of Biology, Damghan University, Damghan, 3671641167, Iran. FAU - Lashkarbolouki, Taghi AU - Lashkarbolouki T AD - School of Biology, Damghan University, Damghan, 3671641167, Iran. FAU - Shabani, Mohammad AU - Shabani M AD - Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran. LA - eng PT - Journal Article DEP - 20181115 PL - United States TA - Neurotox Res JT - Neurotoxicity research JID - 100929017 RN - 0 (Antioxidants) RN - 0 (Neuroprotective Agents) RN - 0LVT1QZ0BA (Homocysteine) RN - 935E97BOY8 (Folic Acid) SB - IM MH - Animals MH - Antioxidants/pharmacology MH - Cerebellar Diseases/chemically induced/drug therapy/metabolism/pathology MH - Cerebellum/*drug effects/*growth & development/metabolism/pathology MH - Folic Acid/blood/*pharmacology MH - Homocysteine/*adverse effects/blood MH - Lipid Peroxidation/drug effects/physiology MH - Male MH - Motor Cortex/drug effects/growth & development/metabolism/pathology MH - Neurodegenerative Diseases/chemically induced/drug therapy/metabolism/pathology MH - Neuroprotective Agents/blood/*pharmacology MH - Oxidative Stress/drug effects/physiology MH - Random Allocation MH - Rats, Wistar OTO - NOTNLM OT - Folic acid OT - Homocysteine OT - Oxidative stress OT - Purkinje cell OT - Rat EDAT- 2018/11/18 06:00 MHDA- 2019/05/16 06:00 CRDT- 2018/11/17 06:00 PHST- 2018/08/08 00:00 [received] PHST- 2018/11/07 00:00 [accepted] PHST- 2018/10/21 00:00 [revised] PHST- 2018/11/18 06:00 [pubmed] PHST- 2019/05/16 06:00 [medline] PHST- 2018/11/17 06:00 [entrez] AID - 10.1007/s12640-018-9979-y [pii] AID - 10.1007/s12640-018-9979-y [doi] PST - ppublish SO - Neurotox Res. 2019 Apr;35(3):724-738. doi: 10.1007/s12640-018-9979-y. Epub 2018 Nov 15.