RESUMEN
Parkinson disease (PD) is a neurodegenerative disease mainly characterized by the loss of nigral dopaminergic neurons in the substantia nigra pars compacta. Patients suffering from PD develop severe motor dysfunctions and a myriad of non-motor symptoms. The treatment mainly consists of increasing central dopaminergic neurotransmission and alleviating motor symptoms, thus promoting severe side effects without modifying the disease's progress. A growing body of evidence suggests a close relationship between neuropeptide S (NPS) and its receptor (NPSR) system in PD: (i) double immunofluorescence labeling studies showed that NPSR is expressed in the nigral tyrosine hydroxylase (TH)-positive neurons; (ii) central administration of NPS increases spontaneous locomotion in naïve rodents; (iii) central administration of NPS ameliorates motor and nonmotor dysfunctions in animal models of PD; (iv) microdialysis studies showed that NPS stimulates dopamine release in naïve and parkinsonian rodents; (v) central injection of NPS decreases oxidative damage to proteins and lipids in the rodent brain; and, (vi) 7 days of central administration of NPS protects from the progressive loss of nigral TH-positive cells in parkinsonian rats. Taken together, the NPS/NPSR system seems to be an emerging therapeutic strategy for alleviating motor and non-motor dysfunctions of PD and, possibly, for slowing disease progress.
RESUMEN
Neuropeptide S (NPS) is a 20-aminoacid peptide that selectively activates a G-protein coupled receptor named NPSR. Preclinical studies have shown that NPSR activation promotes anxiolysis, hyperlocomotion, arousal and weakfullness. Previous findings suggest that dopamine neurotransmission plays a role in the actions of NPS. Based on the close relationship between dopamine and Parkinson disease (PD) and on the evidence that NPSR are expressed on brain dopaminergic nuclei, the present study investigated the effects of NPS in motor deficits induced by intracerebroventricular (icv) administration of the dopaminergic neurotoxin 6-OHDA in the mouse rotarod test. 6-OHDA injection evoked motor deficits and significantly reduced tyrosine hidroxylase (TH)-positive cells in the substantia nigra (SN) and ventral tegmental area. However, a positive correlation was found only between the motor performance of 6-OHDA-injected mice and the number of TH-positive cells in SN. The systemic administration of l-DOPA+benserazide (25+6.25 mg/kg) counteracted 6-OHDA-induced motor deficits in mice. Similar to L-DOPA, the icv injection of NPS (0.1 and 1 nmol) reversed motor deficits evoked by 6-OHDA. In conclusion, NPS attenuated 6-OHDA-induced motor impairments in mice assessed in the rota-rod test. We discussed the beneficial actions of NPS based on a putative facilitation of dopaminergic neurotransmission in the brain. Finally, these findings candidate NPSR agonists as a potential innovative treatment for PD.
Asunto(s)
Adrenérgicos/toxicidad , Trastornos del Movimiento/tratamiento farmacológico , Trastornos del Movimiento/etiología , Oxidopamina/toxicidad , Receptores Acoplados a Proteínas G/uso terapéutico , Análisis de Varianza , Animales , Área Bajo la Curva , Modelos Animales de Enfermedad , Dopaminérgicos/uso terapéutico , Femenino , Levodopa/uso terapéutico , Ratones , Prueba de Desempeño de Rotación con Aceleración Constante , Sustancia Negra/metabolismo , Sustancia Negra/patología , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Electrophysiological and molecular genetic studies have shown that howler monkeys (Alouatta) are unique among all studied platyrrhines: they have the potential to display trichromatic color vision among males and females. This study examined the color discrimination abilities of four howler monkeys (Alouatta caraya) through a series of tasks involving a behavioral paradigm of discrimination learning. The animals were maintained and housed as a group in the Zoological Gardens of Brasília and were tested in their own home cages. Stimuli consisting of pairs of Munsell color chips were presented in random brightness values to assure that discriminations were based on color rather than brightness cues. All the animals (three males, one female) successfully discriminated all the stimulus pairs, including those that would be expected to be difficult for a dichromatic monkey. These results are consistent with the earlier predictions suggesting that howler monkeys are routinely trichromatic.