Neuroprotective effects of agmatine in mice infused with a single intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Filipe C Matheus, Aderbal S Aguiar, Adalberto A Castro, Jardel G Villarinho, Juliano Ferreira, Cláudia P Figueiredo, Roger Walz, Adair R S Santos, Carla I Tasca, Rui D S Prediger

Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, 88049-900 Florianópolis, SC, Brazil.

Behavioural brain research 2012 Dec 1

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We have recently demonstrated that rodents treated intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) suffered impairments in olfactory, cognitive, emotional and motor functions associated with time-dependent disruption of dopaminergic neurotransmission in different brain structures conceivably analogous to those observed during different stages of Parkinson's disease (PD). Agmatine, an endogenous arginine metabolite, has been proposed as a novel neuromodulator that plays protective roles in several models of neuronal cellular damage. In the present study we demonstrated that repeated treatment with agmatine (30 mg/kg, i.p.) during 5 consecutive days increased the survival rate (from 40% to 80%) of 15-month-old C57BL/6 female mice infused with a single intranasal (i.n.) administration of MPTP (1 mg/nostril), improving the general neurological status of the surviving animals. Moreover, pretreatment with agmatine was found to attenuate short-term social memory and locomotor activity impairments observed at different periods after i.n. MPTP administration. These behavioral benefits of exogenous agmatine administration were accompanied by a protection against the MPTP-induced decrease of hippocampal glutamate uptake and loss of dopaminergic neurons in the substantia nigra pars compacta of aging mice, without altering brain monoamine oxidase B (MAO-B) activity. These results provide new insights in experimental models of PD, indicating that agmatine represents a potential therapeutic tool for the management of cognitive and motor symptoms of PD, together with its neuroprotective effects. Copyright © 2012 Elsevier B.V. All rights reserved.

Citation

Filipe C Matheus, Aderbal S Aguiar, Adalberto A Castro, Jardel G Villarinho, Juliano Ferreira, Cláudia P Figueiredo, Roger Walz, Adair R S Santos, Carla I Tasca, Rui D S Prediger. Neuroprotective effects of agmatine in mice infused with a single intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Behavioural brain research. 2012 Dec 1;235(2):263-72