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Algo de ritmos circadianos, de avances de fase inducidos por luz y de resincronización

Laboratory of Chronobiology, Department of Science and Technology, National University of Quilmes, Buenos Aires, Argentina. Algo de ritmos circadianos, de avances de fase inducidos por luz y de resincronización

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Algo de ritmos circadianos, de avances de fase inducidos por luz y de resincronización

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  1. Laboratory of Chronobiology, Department of Science and Technology, National University of Quilmes, Buenos Aires, Argentina. Algo de ritmos circadianos, de avances de fase inducidos por luz y de resincronización Una intro a lo que hacemos con el SCN, con el cGMP, el NO, PKG y la PDE, sin hablar de MAP, ni CRE, CREB, TNF,y menos de tve, BBC, CNN, FOX, BBVA, y bla bla bla.

  2. INTRODUCCION QUIMICO Los ritmos ocurren en todos los niveles de organización CELULAR FISIOLOGICO POBLACIONAL CONDUCTUAL CELULAR Expresión génica, actividad eléctrica, síntesis y liberación de neurotransmisores. FISIOLÓGICO Temperatura, presión arterial, frecuencia cardíaca, niveles de hormonas en sangre. CONDUCTUAL Conducta alimentaria, ciclo sueño/vigilia, actividad locomotora.

  3. AMPLITUDE La Cronobioloia Estudia los Ritmos Bilogicos Propiedades Generales de los ritmos PHASE SHIFT PERIOD PARAMETEROS • PERIODO • AMPLITUD • FASE TIME

  4. Espectro de los Ritmos Biológicos Rhythm Period Example 0,1 sec electroencephalogram 1 sec electrocardiogram Ultradian 6 sec breathing rhythm 60 min pulsatile hormone secretion 90 min sleep staging sleep - wake cycle Circadian 24 hours body temperature 28 days menstrual cycle Infradian 365 days hibernation

  5. light En mamíferos, el reloj biológico se halla en los núcleos supraquiasmaticos (SCN) • Output rhythms • Behavior Suprachiasmatic Nucleus (SCN)

  6. NSQ QO INTRODUCCION Los núcleos supraquiasmáticos (NSQ) son la sede del reloj biológico en mamíferos CARACTERISTICAS NEUROQUIMICAS EXPRESION GENES RELOJ Región dorsomedial EXPRESION RITMICA Región ventrolateral EXPRESION INDUCIDA POR LUZ AVP VASOPRESINA VIPPEPTIDO VASOACTIVO INTESTINAL Calb: Calbindina 3V: TERCER VENTRICULO QO: QUIASMA OPTICO

  7. Principales componentes del Sistema Circadiano • TEMPERATURA • NIVELES HORMONALES • EXPRESION DE PROTEINAS • ACTIVIDAD LOCOMOTORA • ETC. ZEITGEBER(exógeno) oscilador (endógeno) INPUT OUTPUT Ciclo LUZ-OSCURIDAD OSCILADOR Sincronización Acoplamiento

  8. Degradación vía proteosoma CRY CRY PER PER PER CKI CLOCK BMAL Per E-box Genes blanco PER Cry CRY Rev otros INTRODUCCION Mecanismo de oscilación: el reloj molecular NUCLEO CITOPLASMA

  9. L:D (14:10) vs D:D

  10. Phase response curve (PRC)

  11. Light Ca2+ Glu NMDA-R Ca2+ Ca2+-Calmodulin CaMKII Signal transduction pathways responsible of photic mammalian phase advances CaMKII has been implicated in the resetting of the circadian clock by light exposure(Golombek and Ralph, 1994)

  12. Light Ca2+ Glu NMDA-R Ca2+ Ca2+-Calmodulin A role fornNOS in circadian responses to light has been indicated by several pharmacologicaland electrophysiological studies(Melo et al., 1997) NOS CaMKII

  13. Light Ca2+ Glu NMDA-R Ca2+ Ca2+-Calmodulin CaMKII NOS NOS There is a direct pathway between CaMKII and NOS inthe SCN (Agostino et al, 2004, Neurochem Int 44: 617-625)

  14. Light Ca2+ Glu NMDA-R Ca2+ An involvement for the NOS-GC-PKG pathway in light-induced phase advances has been indicated by several studies. Ca2+-Calmodulin Late night (phase advance) CaMKII NOS NO - cGMP induces phase advances in vitro (Prosser y Gillette, 1996) GC cGMP - PKG inhibition blocks light-induced phase advances in vivo (Mathur et al., 1996) PKG

  15. LD Daily and circadian variations of cGMP content in the hamster SCN DD Maximal values were found during the day

  16. LD Daily and circadian variations of cGK activity in the hamster SCN DD Maximal values were found during the day

  17. The GC-PKG pathway is involved light-induced phase advances A: a 5-min light pulse increases cGMP levels at CT 18 but not at CT 14 (modified from Ferreyra and Golombek, 2001). B: PKG activity significantly increased after a 5-min light pulse at CT 18 but was unaffected by the same photic stimulus at CT 14 (Golombek et al, 2004)

  18. Phase advances of the circadian rhythm of locomotor activity are blocked by the NOS inhibitor L-NAME, the GC inhibitor ODQ and the cGK inhibitor KT-5823. On the other hand, the NO donor SNAP significantly increases light induced phase advances(Golombek et al, 2004).

  19. Light Ca2+ Glu NMDA-R Ca2+ NO cGMP GC PKG Ca2+-Calmodulin CaMKII Late Night NOS NO ? Early Night Phase delay ? Phase advance

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