Atorvastatin improves cognitive, emotional and motor impairments induced by intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in rats, an experimental model of Parkinson's disease

• Published in: Brain research 2013-06, Vol.1513, p.103-116
• Main Authors: Castro, Adalberto A, Wiemes, Bárbara P, Matheus, Filipe C, Lapa, Fernanda R, Viola, Giordano G, Santos, Adair R, Tasca, Carla I, Prediger, Rui D
• Format: Article
• Language: English
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - administration & dosage; Administration, Intranasal; Analysis of Variance; Animals; Antiparkinson Agents - therapeutic use; Atorvastatin; Atorvastatin Calcium; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Brain - pathology; cognition; Cognition Disorders - drug therapy; Cognition Disorders - etiology; Cytokines; Cytokines - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Depression; Disease Models, Animal; Food Preferences - drug effects; Heptanoic Acids - therapeutic use; hippocampus; inflammation; interleukin-10; Intranasal; locomotion; Male; Maze Learning - drug effects; Medical sciences; memory; Memory dysfunction; Mood Disorders - drug therapy; Mood Disorders - etiology; Motor Activity - drug effects; MPTP; nerve growth factor; Nerve growth factor (NGF); Nervous system (semeiology, syndromes); Nervous system as a whole; Neuroinflammation; Neurology; neurons; neuroprotective effect; oral administration; Parkinson disease; Parkinson's disease; Parkinsonian Disorders - complications; pathophysiology; Pyrroles - therapeutic use; Rat; Rats; Rats, Wistar; Social Behavior; Sucrose - administration & dosage; Sweetening Agents - administration & dosage; Swimming; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2013.03.029

Abstract Affective disorders and memory impairments precede the classical motor symptoms seen in Parkinson's disease (PD) and the currently approved antiparkinsonian agents do not alleviate the non-motor symptoms as well as the underlying dopaminergic neuron degeneration. On the other hand, there is increasing evidence that inflammation plays a key role in the pathophysiology of PD and that the anti-inflammatory actions of statins are related to their neuroprotective properties against different insults in the CNS. The present data indicates that the oral treatment with atorvastatin (10 mg/kg/day), once a day during 7 consecutive days, was able to prevent short-term memory impairments and depressive-like behavior of rats assessed in the social recognition and forced swimming tests at 7 and 14 days, respectively, after a single intranasal (i.n.) administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1 mg/nostril). Importantly, at this time no significant alterations on the locomotor activity of the animals were observed in the open field test. Moreover, atorvastatin was found to protect against the long-lasting motor deficits evaluated in activity chambers and the loss of dopaminergic neurons in the substantia nigra pars compacta observed at 21 days after i.n. MPTP administration. At this time, despite the absence of spatial memory deficits in the water maze and in concentrations of the cytokines TNF-α, IL-1β and IL-10 in striatum and hippocampus following i.n. MPTP administration, atorvastatin treatment resulted in a significant increase in the striatal and hippocampal levels of nerve growth factor (NGF). These findings reinforce and extend the notion of the neuroprotective potential of atorvastatin and suggest that it may represent a new therapeutic tool for the management of motor and non-motor symptoms of PD.