In circadian terms, human ontogeny is characterized by the emergence of a daily pattern, from a previous ultradian pattern, for most variables during the first 6 months of life. Circadian aging in humans is characterized by a phase advance, accompanied by rhythm fragmentation and flattening. Despite an expanding body of literature focused on distal skin temperature, little information is available about the ontogeny and practically nothing about age-related changes in this rhythm. Thus, the aim was to evaluate the degree of maturation and aging of the circadian pattern of distal skin temperature to identify those parameters that are modified throughout life and could be used to differentiate subjects according to their age. For this, distal skin temperature was measured in 197 volunteers (55 % women), including babies aged 15 days (30 subjects), 1 month (28 subjects), 3 months (31 subjects), and 6 months (10 subjects); young adults aged 19 years (37 subjects); middle-aged persons aged 46 years (27 subjects); older people aged 72 (34 subjects). Circadian system maturation was associated with an increase in amplitude and a reduction in skin temperature during sleep. During adulthood, women showed a more robust pattern (lower fragmentation, and higher night-time temperature, amplitude, circadian function index, and first harmonic relative power); however, these differences were lost with aging, a period of life that was consistently associated with a phase advance of the rhythm. In summary, distal skin temperature pattern can be used as a robust variable to discern between different ages throughout the life.

Title: Cannabinoid receptor ligands prevent dopaminergic neurons death induced by neurotoxic, inflammatory and oxidative stimuli in vitro.Background: During the last 25 years increasing efforts have been invested for the comprehension of the cannabinoid system in a wide range of healthy and pathological conditions. Previous investigations have indicated the possible protective role of synthetic cannabinoids like arachidonyl-2'-chloroethylamide, ACEA (CB1 agonist), during neurodegenerative diseases such as Parkinson's disease. Other synthetic CB1 receptor ligands such as N-(Piperidin-1-yl)-5-(4iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide, AM251, commonly known as an antagonist/inverse agonist, have recently been presented as an allosteric modulator of this receptor. In this study, we show the protective effect of ACEA against oxidative and inflammatory damage in in vitro dopaminergic neurons. Methods and Findings:Neuro2A cells differentiated into dopaminergic-like neurons were challenged with neurotoxic, inflammatory and oxidative treatments, 6-hydroxidopamine (6OHDA), lipopolysaccharide (LPS) and hydrogen peroxide (H 2 O 2 ). Cannabinoid-dependent cell protection was evaluated by means of cellular viability, reactive oxygen species (ROS) production and the pro apoptotic protein caspase 3 expression after CB1 agonist ACEA and antagonist AM251. The ACEA treatment resulted in an increase of cellular viability after the 6OHDA, LPS and H 2 O 2 challenges. When cells were co-treated with ACEA and AM251, an increase in cell death prevention was observed, with a reduction in reactive oxygen species production and caspase 3 expression.Conclusions: Together, we show an ACEA-mediated neuronal protection by means of ROS expression reduction and pro apoptotic protein caspase 3 expression inhibition.

The aim of this study was to investigate the effects of daytime and blood glucose levels on the propagation of cortical spreading depression (SD). Thirty-nine male Wistar rats were used. Animals were housed 5 per cage with a 12-h, light-dark cycle (lights on at 0600 h). Food and water were available ad libitum, and animals were fasted the night before the experiments. Cortical SD was recorded continuously for 3 h using Ag-AgCl agar-Ringer electrodes placed on the parietal cortex. Every 20 min, SD was elicited by 2% KCl stimulation of the frontal cortex for 1 min. After 1 h of SD-recording, blood glucose levels were measured, and animals were injected intravenously either with glucose (40% solution, 1 mL), insulin (0.3 U/100 g of body weight), or mannitol (20% solution, 1 mL). In the middle of the light period, which corresponds to zeitgeber time (ZT)5, 8 animals received glucose, 7 received insulin, and 6 received mannitol. In another experimental set, glucose or insulin was administered at ZT12 (at the end of the light period); 12 rats received glucose, and 6 received insulin. All the animals that received glucose were hyperglycaemic (P<0.01), and the hyperglycaemia was less pronounced in the ZT12 group (P<0.05; Student's t-test). Insulin induced acute hypoglycaemia in animals of both groups (ZT5, P<0.02; ZT12, P<0.05; Student's t-test). Glucose injection at ZT5 reduced SD, whereas the insulin ZT5 group showed increased SD propagation (ANOVA, P<0.05 and 0.01, respectively). Neither glucose nor insulin injection changed SD velocity at ZT12. We concluded that blood glucose levels change the velocity of SD propagation and that these effects are influenced by the daytime. Dark periods seemed to produce a resistance to cortical SD propagation.