title: Pharmacological benefit of I(1)-imidazoline receptors activation and nuclear factor kappa-B (NF-κB) modulation in experimental Huntington's disease.
abstract: Huntington's disease (HD), a neurodegenerative disorder, is characterized by progressive motor dysfunction, emotional disturbances, dementia, weight loss and anxiety. The tremendous amount of research work is required to identify new pharmacological agents of therapeutic utility to combat this condition. This study investigates the effect of selective modulator of I1-imidazoline receptor (moxonidine) as well as nuclear factor kappa-B (NF-κB) (natrium diethyl dithio carbamate trihydrate-NDDCT) on 3-nitropropionic acid (3-NPA) induced experimental HD condition. 3-NPA was used to induce mitochondrial damage and associated HD symptoms in rats. Anxiety was assessed using Elevated plus maze-EPM and learning-memory was assessed using EPM and Morris water maze-MWM. Different biochemical estimations were used to assess brain striatum oxidative stress (lipid peroxide, superoxide dismutase and catalase), nitric oxide levels (nitrite/nitrate), cholinergic activity (brain striatum acetyl cholinesterase activity), and mitochondrial enzyme complex (I, II and IV) activities. 3-NPA has induced anxiety, impaired learning-memory with a reduction in body weight, locomotor activity, grip strength. It has increased brain striatum acetylcholinesterase-AChE activity, oxidative stress (lipid peroxide, nitrite/nitrate, superoxide dismutase and catalase) and impaired mitochondrial complex enzyme (I, II and IV) activities. Tetrabenazine-TBZ (monoamine storage inhibitor) was used as positive control. Treatment with moxonidine, NDDCT and TBZ significantly attenuated 3-NPA induced reduction in body weight, locomotor activity, grip strength, anxiety as well as impaired learning and memory. Administration of these agents attenuated 3-NPA induced various biochemical impairments. Therefore, modulation of I1-imidazoline receptor as well as NF-κB may be considered as potential pharmacological agents for the management of 3-NPA induced HD.
authors.affiliation: Neuropharmacology Lab., Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Uttar Pradesh, India. Electronic address: sharmaslab3@gmail.com.
authors.forename: Surbhi
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Uttar Pradesh, India; CNS Pharmacology, Conscience Research, Pocket F-233, B, Dilshad Garden, Delhi 110095, India. Electronic address: drbhupeshresearch@gmail.com.
authors.forename: Bhupesh
authors.initials: B
authors.lastname: Sharma
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004050:Ditiocarb / Q000494:pharmacology*; D006816:Huntington Disease / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors / Q000378:metabolism; D007859:Learning Disabilities / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D009574:Nitro Compounds; D018697:Nootropic Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011422:Propionates; D051381:Rats; D017208:Rats, Wistar; D013747:Tetrabenazine / Q000494:pharmacology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D007093:Imidazoles; D054755:Imidazoline Receptors; D016328:NF-kappa B; D009574:Nitro Compounds; D018697:Nootropic Agents; D011422:Propionates; C410887:imidazoline I1 receptors; D004050:Ditiocarb; C043482:moxonidine; C015392:3-nitropropionic acid; D013747:Tetrabenazine
keywords: 3-Nitropropionic acid; Mitochondrial enzyme complex; Moxonidine; Natrium diethyl dithio carbamate trihydrate; Tetrabenazine