A network of (autonomic) clock outputs

The circadian clock in the suprachiasmatic nuclei (SCN) is composed of thousands of oscillator neurons, each dependent on the cell-autonomous action of a defined set of circadian clock genes. A major question is still how these individual oscillators are organized into a biological clock that produces a coherent output capable of timing all the different daily changes in behavior and physiology. We investigated which anatomical connections and neurotransmitters are used by the biological clock to control the daily release pattern of a number of hormones. The picture that emerged shows projections contacting target neurons in the medial hypothalamus surrounding the SCN. The activity of these pre-autonomic and neuro-endocrine target neurons is controlled by differentially timed waves of vasopressin, GABA, and glutamate release from SCN terminals, among other factors. Together our data indicate that, with regard to the timing of their main release period within the LD cycle, at least four subpopulations of SCN neurons should be discernible. The different subgroups do not necessarily follow the phenotypic differences among SCN neurons. Thus, different subgroups can be found within neuron populations containing the same neurotransmitter. Remarkably, a similar distinction of four differentially timed subpopulations of SCN neurons was recently also discovered in experiments determining the temporal patterns of rhythmicity in individual SCN neurons by way of the electrophysiology or clock gene expression. Moreover, the specialization of the SCN may go as far as a single body structure, i.e., the SCN seems to contain neurons that specifically target the liver, pineal gland, and adrenal gland.     

Melatonin ingestion after exhaustive late-evening exercise attenuate muscle damage,oxidative stress,and inflammation during intense short term effort in the following day in teenage athletes

ABSTRACT

The present study aimed to investigate whether nocturnal melatonin (MEL) ingestion has beneficial effects against exercise-induced oxidative stress and muscle damage in young athletes. Fourteen healthy-trained teenagers performed two-test sessions separated by at least, 1 week. During each session, participants completed the Running-Based Anaerobic Sprint Test (RAST) at 20:00 h. Then, they ingested a single 10-mg tablet of MEL or Placebo (PLA) in a double-blind randomized order at 22:00 h. The following morning (i.e., 07:30 h), participants performed the same test as the previous night. Blood samples were taken before and after exercise. MEL intake increased the peak power (P_peak) (p < .01), mean power (P_mean) (p < .001) and decreased the total time (TT) (p < .001) and the fatigue index (FI) (p < .05). Furthermore, MEL ingestion attenuated the hematologic parameters before and after exercise (White Blood Cells (WBC: p < .001 and p < .001, respectively); Neutrophiles (NE: p < .001 and p < .001, respectively); Lymphocytes (LY: p < .001 and p < .001, respectively)) and the ultra-sensitive C-reactive protein (us-CRP: p < .001 and p < .001; respectively) compared to PLA. Also, MEL reduced muscle and hepatic damage enzymes before and after exercise (creatine kinase (CK: p < .001 and p < .001; respectively), lactate dehydrogenase (LDH: p < .05 and p < .01; respectively), aspartate aminotransferase (ASAT: p < .01 and p < .001; respectively)), Malondialdehyde (MDA: p < .001 and p < .001; respectively) and Homocysteine (Hcy: p < .001 and p < .001; respectively)) from placebo. Plasma lactate [La] and glucose (GL) remained unchangeable during the two conditions. In summary, acute MEL ingestion after strenuous late-evening exercise attenuated transient leucocytosis and protected against lipid peroxidation and muscle damage induced by strenuous exercise the following morning in healthy male teenage athletes.     

褪黑激素对D-半乳糖处理小鼠学习记忆和脑组织超氧物歧化酶活力的影响

采用Ｍｏｒｒｉｓ水迷宫法和ＮＢＴ法分别检测了褪黑激素对Ｄ－半乳糖处理小鼠的空间学习记忆能力和脑组织超氧物歧化酶活力的影响。结果表明,Ｄ－半乳糖对小鼠的逃避潜伏期无显著影响,但降低小鼠的穿环系数,还促使小鼠的脑组织超氧物歧化酶活力明显升高;褪黑激素可提高小鼠的空间学习记忆能力,降低Ｄ－半乳糖所引起的超氧物歧化酶活力升高。     

Tentative immunohistochemical demonstration of melatonin in the rat pineal gland

Summary In the present study an attempt was made to demonstrate melatonin in the rat pineal gland by means of immunohistochemistry. The anti-body used was raised against 5-methoxy-N-acetyltryptophan which is chemically similar to melatonin. Specific fluorescence was demonstrable only in pineals from rats killed during the night, when melatonin formation is high. It was restricted to parenchymal cells lying in a marginal zone of the organ. These results are discussed in relation to a subdivision of the pineal parenchyma into cortical and medullary areas.Supported by a grant of the Deutsche Forschungsgemeinschaft (VO 135/4) within the Schwerpunktprogramm Neuroendokrinologie     

Vasotocin, melatonin and narcolepsy: Possible involvement of the pineal gland in its patho-physiological mechanism

Both the pineal nonapeptide hormone arginine vasotocin (AVT) (2.5 μg) administered intra-nasally and the pineal indole melatonin (50 mg) administered intravenously to three male narcoleptics (two with auxiliary symptoms and one with sleep attacks only), dramatically increased the amount of REM sleep and decreased REM sleep latency. The duration of the sleep onset REM periods in the two narcoleptics with auxiliary symptoms increased by more than 100 percent after AVT and melatonin administration. In the narcoleptic with sleep attacks only both AVT and melatonin induced REM periods at sleep onset. The hypothesis is advanced that narcolepsy represents an impairment of the melatonin-AVT control in the induction and circadian organization of REM sleep associated with an immaturity of REM triggering centers.     

Effects of Neonatal Melatonin Administration on the Extra-Hypothalamic Regions in Rat Brains: Effects on the Serotonergic System

The effects of 100g melatonin injection at postnatal day 5 (PD 5) on the development of the central serotonergic systems in male and female rats were investigated. The contents of serotonin (5-HT) and 5-hydroxy-3-indolacetic acid (5-HIAA) were measured in several extra-hypothalamic regions at 3, 10 and 42 weeks of age. The neonatal melatonin administration increased both 5-HT and 5-HIAA levels in the striatum throughout the examined period. In the hippocampus, an increase in 5-HIAA contents by neonatal melatonin administration was found at 3 weeks but not 10 or 42 weeks of age. There were no significant differences in the effects of melatonin between male and female rats. These results indicated that exogenous melatonin administration during the early neonatal period influenced the development of the serotonergic systems in extrahypothalamic regions including the hippocampus and the striatum.     

Age dependent expression of melatonin membrane receptor (MT1, MT2) and its role in regulation of nitrosative stress in tropical rodent Funambulus pennanti

Age-dependent declining level of melatonin induces free radical load and thereby deteriorates immune function. However, reports are lacking about age-dependent melatonin membrane receptor (MT1 & MT2) expression, their role in regulation of reactive nitrogen species (RNS) and eventually how they affect immunity of a tropical rodent F. pennanti. We checked MT1R, MT2R and iNOS expression in lymphoid organs of young middle and old aged squirrels. Nitrite and nitrate ion concentration (NOx) in lymphoid organs, testes and plasma, lymphocyte proliferation and IL-2 level was recorded. Age-dependent decrease in MT1 and MT2 receptor expression, lymphocyte proliferation, IL-2 level and increased RNS in lymphoid organs, testes and plasma was observed with decreased circulatory melatonin. Androgen and AR expression was increased in middle-aged while declined in old-aged squirrels. Present study suggests that age associated immunosenescence is consequence of increased RNS which might have important relationship with melatonin membrane receptors in F. pennanti.     

Norepinephrine Release in the Rat Pineal Gland: The Input from the Biological Clock Measured by In Vivo Microdialysis

Abstract: The sympathetic innervation of the rat pineal gland was investigated, measuring the norepinephrine (NE) release by on-line in vivo microdialysis. NE was assayed using an HPLC method with precolumn derivatization and fluorescence detection. Its high sensitivity and reliability made it very suitable to monitor the low levels of NE in the dialysates (12.5 fmol during nighttime, 3 fmol during daytime). To increase NE levels, the monoamine reuptake inhibitor cocaine was added to Ringer's solution at concentrations of 10⁻⁶ and 10⁻⁵ M . This resulted in increases of neurotransmitter output of 167 and 219%, respectively, but did not change the qualitative and/or quantitative outcome of other experiments. Perfusion with 10⁻⁶ M tetrodotoxin for 1 h resulted in a decrease of the NE release by >80%, whereas perfusion with the α₂-receptor antagonist yohimbine caused a twofold increase. These results indicate that the NE release in the rat pineal was of neuronal origin and regulated by a negative feedback mechanism involving inhibitory presynaptic α₂-receptors. Long-term (i.e., 16 h) measurements are described, showing the circadian properties of NE release. A pronounced rhythm is reported, showing extremely sharp transitions between low daytime and high nighttime values. Increases and decreases are reported to occur within the duration of collecting one sample (20 min). For comparison, the rhythm of melatonin release was also recorded. The on and off switches of the sympathetic input correlated well with the circadian rhythm of melatonin release and can thus be considered as the primary clock signal, inducing the nightly production of melatonin.     

Geomagnetic Field Effect on Affective and Cognitive Competence in Preschool

The goal of our research was to study the effect of geomagnetic field (GMF) disturbances, in terms of K, K_p, A_k, A_p, and SK indices, on children's affective (emotional) and cognitive competence during different forms of organization of pretend play. We studied two forms of management of the playing process: 1) teacher‐directed frontal play with simultaneous involvement of all children in the classroom and 2) child‐directed play in various small groups. Twenty‐six observations were performed on 51 children in two mixed‐age classrooms. The mean age of the children was 4.6 years, with age span from 3 to 6 years. We found a significant increase in cognitive behavior during child‐directed play in groups compared with frontal, teacher‐directed management of the lesson. During child‐directed play children's behavior was negatively correlated with geomagnetic disturbance in both affective and cognitive domains (R = ? 0.47, p < 0.029, n = 21) as compared with teacher‐directed play where there was no significant interaction. We believe the dependence of the GMF effect on the type of the organization of the educational process is explained by the less‐stressful environment of the child‐directed playing conditions compared with teacher‐directed in which the directive role of the teacher can mask a possible GMF effect.