title: Neuroprotective effects of agmatine in mice infused with a single intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
abstract: 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.
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, 88049-900 Florianópolis, SC, Brazil.
authors.forename: Filipe C
authors.initials: FC
authors.lastname: Matheus
authors.forename: Aderbal S
authors.initials: AS
authors.lastname: Aguiar
authors.forename: Adalberto A
authors.initials: AA
authors.lastname: Castro
authors.forename: Jardel G
authors.initials: JG
authors.lastname: Villarinho
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
authors.forename: Cláudia P
authors.initials: CP
authors.lastname: Figueiredo
authors.forename: Roger
authors.initials: R
authors.lastname: Walz
authors.forename: Adair R S
authors.initials: AR
authors.lastname: Santos
authors.forename: Carla I
authors.initials: CI
authors.lastname: Tasca
authors.forename: Rui D S
authors.initials: RD
authors.lastname: Prediger
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage*; D000281:Administration, Intranasal / Q000379:methods; D000376:Agmatine / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020734:Parkinsonian Disorders / Q000209:etiology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D021641:Recognition, Psychology / Q000187:drug effects; D012919:Social Behavior; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology; D016019:Survival Analysis; D014316:Tritium / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D014316:Tritium; D018698:Glutamic Acid; D000376:Agmatine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase