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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.
Brain Res. 2013 Jun 04; 1513:103-16.BR

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 (10mg/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) (1mg/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.

Authors+Show Affiliations

Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23548600

Citation

Castro, Adalberto A., et al. "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." Brain Research, vol. 1513, 2013, pp. 103-16.
Castro AA, Wiemes BP, Matheus FC, et al. 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. Brain Res. 2013;1513:103-16.
Castro, A. A., Wiemes, B. P., Matheus, F. C., Lapa, F. R., Viola, G. G., Santos, A. R., Tasca, C. I., & Prediger, R. D. (2013). 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. Brain Research, 1513, 103-16. https://doi.org/10.1016/j.brainres.2013.03.029
Castro AA, et al. 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. Brain Res. 2013 Jun 4;1513:103-16. PubMed PMID: 23548600.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Castro,Adalberto A, AU - Wiemes,Bárbara P, AU - Matheus,Filipe C, AU - Lapa,Fernanda R, AU - Viola,Giordano G, AU - Santos,Adair R, AU - Tasca,Carla I, AU - Prediger,Rui D, Y1 - 2013/03/30/ PY - 2012/07/17/received PY - 2013/03/01/revised PY - 2013/03/19/accepted PY - 2013/4/4/entrez PY - 2013/4/4/pubmed PY - 2013/12/18/medline SP - 103 EP - 16 JF - Brain research JO - Brain Res VL - 1513 N2 - 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 (10mg/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) (1mg/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. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/23548600/Atorvastatin_improves_cognitive_emotional_and_motor_impairments_induced_by_intranasal_1_methyl_4_phenyl_1236_tetrahydropyridine__MPTP__administration_in_rats_an_experimental_model_of_Parkinson's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(13)00451-4 DB - PRIME DP - Unbound Medicine ER -