title: Memantine exerts functional recovery by improving BDNF and GDNF expression in 3-nitropropionic acid intoxicated mice.
abstract: Memantine (MN), a NMDA blocker is well known for its protective effect against various neurodegenerative diseases. However, its role in improving motor function and regulation of neurotrophic factors in Huntington's disease (HD) has not been studied yet. In the present study, we have investigated the effect of MN against 3-nitropropionic acid (3NP), induced motor impairment, and alterations in the expression of brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in mice brain. Further, its role in mitochondrial function was assessed by measuring succinate dehydrogenase (SDH) activity. Glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN) immunoreactivity were studied to evaluate the role of MN on glial and neuronal function. Its effect on apoptosis was adjudged by studying the expression of apoptotic markers. MN restored motor functions with an associated up-regulation in neurotrophin expression. MN also enhanced brain SDH activity and decreased glutamate content. MN ameliorated striatal neuronal loss, reduced GFAP immunoreactivity, and exhibited protective effect against neuronal apoptosis. Data from the current study demonstrated that MN exerted neuroprotective effect against 3NP induced neuropathology. Restoration of motor function by MN might be through regulation of neurotrophin expression. MN can therefore be a useful therapeutic choice in the symptomatic management of HD.
authors.affiliation: Centre for Toxicology and Developmental Research, Sri Ramachandra University, Chennai 600116, India; Department of Biotechnology, Dr. M.G.R. Educational and Research Institute, Maduravoyal, Chennai 600095, India.
authors.forename: Vijayan
authors.initials: V
authors.lastname: Ranju
authors.affiliation: Centre for Toxicology and Developmental Research, Sri Ramachandra University, Chennai 600116, India; Department of Biotechnology, Dr. M.G.R. Educational and Research Institute, Maduravoyal, Chennai 600095, India.
authors.forename: Sekar
authors.initials: S
authors.lastname: Sathiya
authors.affiliation: Centre for Toxicology and Developmental Research, Sri Ramachandra University, Chennai 600116, India.
authors.forename: Periyathambi
authors.initials: P
authors.lastname: Kalaivani
authors.affiliation: Centre for Toxicology and Developmental Research, Sri Ramachandra University, Chennai 600116, India.
authors.forename: Raju Jyothi
authors.initials: RJ
authors.lastname: Priya
authors.affiliation: Centre for Toxicology and Developmental Research, Sri Ramachandra University, Chennai 600116, India. Electronic address: ceftpublications@gmail.com.
authors.forename: Chidambaram
authors.initials: C
authors.lastname: Saravana Babu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004268:DNA-Binding Proteins; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009574:Nitro Compounds / Q000633:toxicity*; D009687:Nuclear Proteins / Q000378:metabolism; D011422:Propionates / Q000633:toxicity*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004268:DNA-Binding Proteins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009574:Nitro Compounds; D009687:Nuclear Proteins; D011422:Propionates; D016194:Receptors, N-Methyl-D-Aspartate; D013385:Succinate Dehydrogenase; C015392:3-nitropropionic acid; D008559:Memantine
keywords: 3NP; BDNF; GDNF; GFAP; Memantine; NeuN