title: Beneficial effects of sodium butyrate in 6-OHDA induced neurotoxicity and behavioral abnormalities: Modulation of histone deacetylase activity.
abstract: Parkinson's disease (PD) is the second most common neurodegenerative disorder. Recent studies have investigated the involvement of epigenetic modifications in PD. Histone deacetylase (HDAC) inhibitors have been reported to be beneficial in cognitive and motor deficit states. The present study was designed to investigate the effect of sodium butyrate, a HDAC inhibitor in 6-hydroxydopamine (6-OHDA) - induced experimental PD like symptoms in rats. To produce motor deficit, 6-OHDA was administered unilaterally in the right medial forebrain bundle. Three weeks after 6-OHDA administration, the rats were challenged with apomorphine. Following this, the animals were treated with sodium butyrate (150 and 300 mg/kg i.p.) once daily for 14 days. Movement abnormalities were assessed by battery of behavioral tests. Biochemically, oxidative stress markers, neuroinflammation and dopamine were measured in striatal brain homogenate. Further, to explore the molecular mechanism(s), we measured the level of global H3 histone acetylation and brain derived neurotrophic factor (BDNF). 6-OHDA administration results in significant motor deficit along with reduction in striatal dopamine level. 6-OHDA treated rats showed elevated oxidative stress and neuroinflammatory markers. Treatment with sodium butyrate results in significant attenuation of motor deficits and increased striatal dopamine level. Moreover, sodium butyrate treatment attenuated the oxidative stress and neuroinflammatory markers. These effects occur concurrently with increased global H3 histone acetylation and BDNF levels. Thus, the observed results of the present study are indicative for the therapeutic potential of HDAC inhibitors in PD.
authors.affiliation: Neuropharmacology Division, Department of Pharmacy, Birla Institute of Technology and Science, Pilani, 333031 Rajasthan, India.
authors.forename: Sorabh
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Neuropharmacology Division, Department of Pharmacy, Birla Institute of Technology and Science, Pilani, 333031 Rajasthan, India. Electronic address: taliyanraja@gmail.com.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Taliyan
authors.affiliation: Neuropharmacology Division, Department of Pharmacy, Birla Institute of Technology and Science, Pilani, 333031 Rajasthan, India.
authors.forename: Sumel
authors.initials: S
authors.lastname: Singh
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D020148:Butyric Acid / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006633:Histamine Antagonists / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D019208:Brain-Derived Neurotrophic Factor; D018491:Dopamine Agonists; D006633:Histamine Antagonists; D014409:Tumor Necrosis Factor-alpha; D020148:Butyric Acid; D016627:Oxidopamine; D006655:Histone Deacetylases; D001058:Apomorphine; D004298:Dopamine
keywords: 6-OHDA; HDAC inhibitors; Histone acetylation; Histone deacetylases; Parkinson’s disease; Sodium butyrate