RESUMEN
Parkinson's disease (PD) is the second most common severe neurodegenerative disorder that is characterized by progressive degeneration of dopaminergic neurons (DA neurons) in the substantia nigra pars compacta (SNpc) region of the brain. In the present study, we investigated the effects of the synthetic regulatory peptides Semax (analog of an ACTH 4-10 fragment (ACTH4-10)) and Selank (analog of immunomodulatory taftsin) on behavior of rats with 6-hydroxidopamine (6-OHDA) induced PD-like parkinsonism. It was showed that both peptides did not affect motor activity of rats in elevated cross shaped maze and passive defensive behavior of the animals. At the same time, Selank decreased level of anxiety of rats with toxic damage of DA neurons in elevated cross shaped maze. Previously such effects of Selank were revealed in healthy rodents (rats and mice) with different models of psycho-emotional stress. Therefore, toxic damage of substantia nigra does not affect the response of the rat organism on this peptide.
Asunto(s)
Enfermedad de Parkinson/tratamiento farmacológico , Trastornos Parkinsonianos/tratamiento farmacológico , Hormona Adrenocorticotrópica/análogos & derivados , Hormona Adrenocorticotrópica/uso terapéutico , Animales , Ansiedad/tratamiento farmacológico , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/metabolismo , Masculino , Oligopéptidos/uso terapéutico , Oxidopamina/toxicidad , Enfermedad de Parkinson/etiología , Trastornos Parkinsonianos/inducido químicamente , Porción Compacta de la Sustancia Negra/efectos de los fármacos , Porción Compacta de la Sustancia Negra/metabolismo , Fragmentos de Péptidos/uso terapéutico , RatasRESUMEN
The effect of single and course administration of Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) in the dose 200 microg/kg on the rat hippocampus transcriptional profile were studied using cDNA microarray technology. It was shown that mRNA levels of 36 genes changed more than 2-fold after a single intranasal Selank administration, and 20 genes--after course administration. It should be noted that most of them encode proteins associated with the plasma membrane (including transmembrane proteins). This suggests that Selank is able to regulate ion homeostasis of hippocampal cells and thereby modulate different ion-dependent processes, which include the processes of learning and memory formation.
Asunto(s)
Hipocampo/metabolismo , Homeostasis/efectos de los fármacos , Oligopéptidos/administración & dosificación , Transcriptoma/genética , Animales , Línea Celular , Membrana Celular/efectos de los fármacos , Hipocampo/citología , Hipocampo/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Ratas , Transcriptoma/efectos de los fármacosRESUMEN
A study of the immunomodulating effect of selank showed that the total peptide and its fragment significantly change the expression of the genes for chemokines, cytokines, and their receptors in mouse spleen 6 and 24 h after administration of a single dose. Changes in the mRNA level of the majority of the genes under study were similarly observed after the administration of Gly-Pro, which was earlier identified as a selank pharmacophor, a minimum fragment with anitiviral activity. Pharmacological preparations based on endogenous regulatory peptides are studied intensely because they are the most promising class of drugs and have almost no side effects. The class includes selank, which is a synthetic analog of taftsin. Selank exerts anxiolytic and nootropic effects and, on the other hand, has pronounced antiviral properties.