Age-related changes in circadian rhythm of serotonin synthesis in ring doves: effects of increased tryptophan ingestion.

Alterations in the function of the hypothalamic suprachiasmatic nucleus (SCN) with age have been reported. As serotonin is an important regulator of the circadian clock located in SCN, this work studied the changes produced in the synthesis of serotonin with age using the accumulation of 5-HTP after decarboxylase inhibition as a measure of serotonin synthesis in the brain in vivo, in young and old ring doves at the onset of lights-on and lights-off. A diurnal cycle in tryptophan hydroxylation was observed in young animals, with an increased daylight synthesis and metabolism of 5-HT in hippocampus, neostriatum and hypothalamus. A single dose of melatonin (1 mg/kg, i.p., 1 h) at lighttime produced an inhibitory effect on the synthesis of 5-HT. In contrast, differences in 5-HT synthesis and metabolism between day and night disappeared in old animals indicating an absence of a circadian rhythm in 5-HT synthesis and metabolism. The administration of L-tryptophan (240 mg/kg, i.p.) strongly increased the 5-HT synthesis in young animals only during lights-off time while it increased in old ones irrespective of the administration time. These results suggest that the supplemental administration of tryptophan might aid to improve the descent in 5-HT that normally occurs, as animals get old.

Age related changes in the activity-rest circadian rhythms and c-fos expression of ring doves with aging. Effects of tryptophan intake.

Age related changes in the circadian rhythms and sleep quality has been linked with impairment in the function of the suprachiasmatic nucleus (SCN) and melatonin secretion. The precursor of melatonin, serotonin (5-HT) is a neurotransmitter involved in the synchronisation of the circadian clock located in SCN, which shows decreased levels with age. The present work studied the effects of L-tryptophan, the precursor of 5-HT, on the circadian activity-rest rhythm and c-fos expression in the SCN of young and old ring doves, animals diurnal and monocyclic as humans. Two hours before the onset of dark phase, animals housed in cages equipped for activity recording and maintained under 12/12 L/D conditions, received orally L-tryptophan (100 and 240 mg/kg) and, for comparative purposes, melatonin (2.5 and 5 mg/kg). The administration of both L-tryptophan and melatonin reduced the nocturnal activity of all ring doves although only the highest doses were effective in old ones. A reduced amplitude in the activity-rest rhythm was observed in old animals in comparison to youngest, but it was increased after the treatments. Sleep parameters, calculated from the activity data, indicated a worsened sleep quality in old animals but it was improved with the treatments. In addition, the expression of c-fos in the SCN was reduced after both mentioned treatments. The results point to the SCN as a target for the observed nocturnal effects of L-tryptophan and melatonin, and support the supplemental administration of the essential amino acid L-tryptophan to reverse the disturbances of the circadian activity-rest cycle related with ageing.

Mammalian sleep may have no adaptive advantage over simple activity-rest cycles.

The adaptive value of sleep remains unknown in spite of the intense research performed throughout the last decades. However, few sleep researchers are aware of the difficulties posed by the blind acceptance of an extreme adaptationist viewpoint. Under this philosophy, every anatomical and functional detail present in a living being should have a positive adaptive value, a position that has been considered as rather doubtful. In this report, it is proposed that most of the physiological changes used for mammalian sleep definition could be mere by-products of other true adaptations, such as the ontogenetic and phylogenetic development of the nervous system. As a result, complex mammalian sleep could have no adaptive value over that of the simplest forms of rest-activity cycles present in all living forms. In addition, it is proposed that the absence of adaptive value should, by default, be the first option regarding the function of sleep. Besides, the burden of the proof should be always charged over the proponents of every particular adaptive function. As this proof has not been reached, it is the absence of function for sleep which should be taken for granted.

Evidence of state-dependent interhemispheric relationships in lizard EEG during the awake state.

The electroencephalogram (EEG) from both hemispheres of eight Canary lizards Gallotia galloti was registered at 25 degrees C and 35 degrees C during awake state with open eyes (OE) and closed eyes. The possible interdependence between the recorded EEGs was assessed by means of newly developed methods of multivariate nonlinear time-series analysis. The interdependence turned out to be significant and greater for the OE state at both temperatures, although it was of linear type in most of the cases. We conclude that the methods can be successfully applied to study the interdependence between noisy, low-amplitude EEGs.

Human Sleep Apneas and Animal Diving Reflexes: The Comparative Link.

Adaptations to survive periods of limited access to oxygen should have been favored along the evolution of vertebrates. Paradigmatic examples of this adaptation are the diving animals, which can sustain prolonged and repetitive periods of anoxia. These animals support what would be considered a severe gas imbalance in their internal environment thanks to three main strategies: increased oxygen stores, resistance to asphyxia, and reduced metabolic expenditure during the apneic intervals. However, diving animals developed their abilities from very old life-sustaining responses that should have been used on many other occasions. Humans with sleep apneas perhaps share many physiological adaptations with diving animals. We review here the extent of such similarities and offer clear evidence of its existence and suggest possible research lines that could improve the clinical knowledge about this condition.

Chrononutrition: use of dissociated day/night infant milk formulas to improve the development of the wake-sleep rhythms. Effects of tryptophan.

Three different lactation experiments have been tested in a double blind procedure for 3 weeks, to improve sleep-wake patterns in infants. In a control experiment, standard infant commercial milk (1.5% tryptophan) was administered without changes during the day. In a second control (inverse), enriched milk (3.4% tryptophan) was given during light-time (06.00-18.00h), and standard commercial milk during night-time (18.00-06.00h). During the experimental week, the infants received standard milk during light-time and tryptophan enriched milk during night-time. The infants receiving the enriched formula during dark time showed improvements in the sleep parameters studied, and no statistical differences were found between the two control lactations. The urinary metabolites of serotonin suggest that the observed improvements were due to an increased use of serotonin to melatonin synthesis. In conclusion, the chronobiological changes in the normal components of the diet can improve infantile development of sleep/wake rhythms.

Opposite effects of tryptophan intake on motor activity in ring doves (diurnal) and rats (nocturnal).

The role of l-tryptophan as precursor of serotonin and melatonin synthesis on activity-rest rhythm was studied in ring doves, Streptopelia risoria, as a representative of diurnal animals and rats, Rattus norvegicus, as a typical nocturnal one. The animals were housed in cages equipped for horizontal activity recording in a thermostatized chamber and submitted to a 12/12h light/dark photoperiod (lights on at 08:00 h). After acclimatization, the animals received vehicle (methylcellulose) and l-tryptophan (240 mg/kg) by esophagic cannula 2h before the onset of either light or dark phase. Also, oral melatonin (2.5mg/kg) was tested for comparative purposes. After nocturnal l-tryptophan administration, rats showed increased activity (149%), while the opposite occurred in ring doves (39% decrease). No significant changes were found after diurnal l-tryptophan intake in either species. Melatonin produced effects similar to those of l-tryptophan. These results suggest that the effects of l-tryptophan administration are dependent on the nocturnal/diurnal habits of the studied species and, most probably, are mediated by increased melatonin synthesis.