title: Apocyanin, NADPH oxidase inhibitor prevents lipopolysaccharide induced α-synuclein aggregation and ameliorates motor function deficits in rats: Possible role of biochemical and inflammatory alterations.
abstract: Parkinson's disease (PD), is an age-related, progressive neurodegenerative disorder that affects movement and is characterized by the loss of dopaminergic neurons in the nigrostriatal region. Although the clinical and pathological features of PD are complex, recent studies have indicated that microglial NADPH oxidase play a key role in its pathology. A little information is available regarding the role of apocyanin, an NADPH oxidase inhibitor, in ameliorating α-synuclein aggregation and neurobehavioral consequences of PD. Therefore, the present study evaluated its therapeutic potentials for the treatment of neurobehavioral consequences in lipolysaccharide (LPS) induced PD model. For the establishment of PD model LPS (5 μg/5 μl PBS) was injected into the Substantia nigra (SN) of rats. Apocyanin (10mg/kgb.wt) was injected intraperitoneal. Statistical analysis revealed that apocynin significantly ameliorated LPS induced inflammatory response characterized by NFkB, TNF-α and IL-1β upregulation as assessed by ELISA. It also prevented dopaminergic neurons from toxic insult of LPS as indicated by inhibition of apoptotic markers i.e., caspase 3 and caspase 9 as depicted from RT-PCR and ELISA studies. This was further supported by TUNEL assay for DNA fragmentation. Effectiveness of apocyanin in protecting dopaminergic neuronal degeneration was further confirmed by assessment of α-synuclein deposition as depicted by IHC analysis. Consequently, an improvement in the behavioral outcome was observed following apocyanin treatment as depicted from various behavioral tests performed. Hence the data suggests that specific NADPH oxidase inhibitors, such as apocynin, may provide a new therapeutic approach to the control of neurological disabilities induced by LPS induced PD.
authors.affiliation: Department of Biophysics, Panjab University, Chandigarh 160014, India. Electronic address: jaitly_neha@rediffmail.com.
authors.forename: Neha
authors.initials: N
authors.lastname: Sharma
authors.affiliation: Department of Biophysics, Panjab University, Chandigarh 160014, India.
authors.forename: Monika
authors.initials: M
authors.lastname: Kapoor
authors.affiliation: Department of Biophysics, Panjab University, Chandigarh 160014, India. Electronic address: bnehru@pu.ac.in.
authors.forename: Bimla
authors.initials: B
authors.lastname: Nehru
mesh_terms: D000098:Acetophenones / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D016207:Cytokines / Q000187:drug effects*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051844:alpha-Synuclein / Q000187:drug effects*
chemical_list: D000098:Acetophenones; D016207:Cytokines; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D051844:alpha-Synuclein; C056165:acetovanillone; D019255:NADPH Oxidases
keywords: Apocyanin; Cytokines; Lipopolysaccharide; NADPH oxidase complex; Neurodegeneration; α-Synuclein