title: Acetyl-l-carnitine protects dopaminergic nigrostriatal pathway in 6-hydroxydopamine-induced model of Parkinson's disease in the rat.
abstract: Parkinson's disease (PD) is a movement disorder and the second most common neurodegenerative disease worldwide in which nigrostriatal dopaminergic neurons within substantia nigra pars compacta (SNC) are lost, with clinical motor and non-motor symptoms including bradykinesia, resting tremor, rigidity, stooping posture and cognitive deficits. This study was undertaken to evaluate the neuroprotective potential of acetyl-l-carnitine (ALC) against unilateral striatal 6-hydroxydopamine (6-OHDA)-induced model of PD and to explore some involved mechanisms. In this experimental study, intrastriatal 6-OHDA-lesioned rats received ALC at doses of 100 or 200mg/kg/day for 1 week. ALC (200mg/kg) lowered apomorphine-induced rotational asymmetry and reduced the latency to initiate and the total time in the narrow beam test, reduced striatal malondialdehyde (MDA), increased catalase activity and glutathione (GSH) level, prevented reduction of nigral tyrosine hydroxylase (TH)-positive neurons and striatal TH-immunoreactivity, and lowered striatal glial fibrillary acidic protein (GFAP) and its immunoreactivity as an indicator of astrogliosis, and nuclear factor NF-kappa B and Toll-like receptor 4 (TLR4) as reliable markers of neuroinflammation. Meanwhile, ALC at both doses mitigated nigral DNA fragmentation as a valuable marker of apoptosis. The results of this study clearly suggest the neuroprotective effect of ALC in 6-OHDA-induced model of PD through abrogation of neuroinflammation, apoptosis, astrogliosis, and oxidative stress and it may be put forward as an ancillary therapeutic candidate for controlling PD.
authors.affiliation: Neurophysiology Research Center, Shahed University, Tehran, Iran.
authors.forename: Siamak
authors.initials: S
authors.lastname: Afshin-Majd
authors.affiliation: School of Medicine, Shahed University, Tehran, Iran.
authors.forename: Keyhan
authors.initials: K
authors.lastname: Bashiri
authors.affiliation: Neurophysiology Research Center, Shahed University, Tehran, Iran. Electronic address: kiasalari@shahed.ac.ir.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Kiasalari
authors.affiliation: Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Tourandokht
authors.initials: T
authors.lastname: Baluchnejadmojarad
authors.affiliation: Department of Anatomy and Pathology, School of Medicine, Shahed University, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Sedaghat
authors.affiliation: Neurophysiology Research Center, Shahed University, Tehran, Iran. Electronic address: mehjour@yahoo.com.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Roghani
mesh_terms: D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects*; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D009434:Neural Pathways / Q000187:drug effects* / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000517:prevention & control* / Q000523:psychology; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D013565:Sympatholytics
chemical_list: D018491:Dopamine Agonists; D018697:Nootropic Agents; D013565:Sympatholytics; D000108:Acetylcarnitine; D016627:Oxidopamine; D001058:Apomorphine
keywords: 6-Hydroxydopamine; Acetyl-l-carnitine; Apoptosis; Neuroinflammation; Oxidative stress; Parkinson’s disease