Core body temperature varies according to the time of exercise without affecting orexin-A production in the dorsal hypothalamus in male rats.

Physical exercise differentially increases body temperature according to the time of day, which shows the importance of circadian rhythm in thermal regulation. Given its contribution in central pathways involved in thermoregulation, orexin A could play a role in the regulation of core body temperature during and after exercise. To test this hypothesis, we assessed the effect of exercise, performed at two times of day, on core temperature and on the amount of orexin A in the production zone, i.e., the dorsal hypothalamus. Forty-nine male Wistar rats underwent forced treadmill exercise during the HG phase and HL phase of core temperature. Basal core temperature was recorded continuously for 48 h by implanted telemetric sensors in 11 rats. Regulation of core temperature during exercise (20 min) and after each exercise (60 min) was modeled with a modified logistic-type function. During HG exercise, core temperature curve reached a significantly higher maximum (asymptote: +0.70 ± 0.10 °C) and took longer to attain the strongest inclination of the core temperature regulation curve (Xmid: 3.46 ± 0.72 min). After HG exercise, time of recovery was significantly longer than after HL exercise. In male rats, thermoregulatory response to acute physical exercise was influenced by the time of day. There was no effect of either physical activity or time of day on the level of orexin A in the dorsal hypothalamus. Our results suggest that orexin A in the dorsal hypothalamus is not involved in the effects of physical exercise on thermoregulation.

Validation of e-Celsius gastrointestinal telemetry system as measure of core temperature.

The main objective of this study was to validate gastrointestinal measurement with the e-Celsius® system composed of an ingestible electronic capsule and a monitor. Twenty-three healthy volunteers aged 18-59 years stayed at the hospital for 24 h under fasting conditions. They were only allowed for quiet activity and were asked to keep their sleeping habits. Subjects ingested a Jonah capsule and an e-Celsius® capsule, and a rectal probe and an esophageal probe were inserted. Mean temperature measured by the e-Celsius® device was lower than that measured by Vitalsense® (-0.12 ± 0.22°C; p < 0.001) and the rectal probe (-0.11 ± 0.03°C; p = 0.003) and higher than that measured by the esophageal probe (0.17 ± 0.05; p = 0.006). Mean difference (bias) and 95% confidence intervals between temperature of e-Celsius capsule, Vitalsense Jonah capsule, esophageal probe, and rectal probe were computed using Bland and Altman procedure. The magnitude of the measurement bias is significantly greater when comparing the e-Celsius® and the Vitalsense® device pair with any other device pairs containing the esophageal probe. Amplitude of confidence interval between the e-Celsius® system and the Vitalsense® system was 0.67°C. This amplitude was significantly lower than those of the esophageal probe-e-Celsius® pairing (0.83°C; p = 0.027), of the esophageal probe-Vitalsense (0.78°C; p = 0.046) and of the esophageal probe-rectal probe (0.83°C; p = 0.002). The statistical analysis did not reveal any effect of time on the amplitude of bias, whatever the device concerned. When comparing missing data rate of the e-Celsius® system (0.23 ± 0.15%) and the Vitalsense® devices (0.70 ± 0.11%) during the whole experiment, no differences was observed (p = 0.09). The e-Celsius® system could be used when a continuous following of internal temperature is needed.

High-frequency stimulation of the hippocampus blocks fear learning sensitization and return of extinguished fear.

Patients with post-traumatic stress disorder (PTSD) present hippocampal (HPC) dysfunction, which may facilitate fear-related phenomena such as fear learning sensitization (i.e. potentiation of fear acquisition by initial fear conditioning (FC1)) and fear return (i.e. reactivation of extinguished fear). Fear return is sensitive to HPC high-frequency stimulation (HFS) in rats. The goal of the present study was to examine whether fear learning sensitization is also sensitive to HPC HFS in rats. We found in control conditions that, after FC1 (with 15 shock administrations) and extinction, conditioning in a different context with one shock administration was potentiated (proactive effect) and associated with fear return in the initial context (retroactive effect). Both phenomena were prevented by HPC HFS applied before the second conditioning. We also found that the effect of HPC HFS on fear learning sensitization required initial extinction. These findings suggest a pivotal role of the HPC in preventing proactive and retroactive effects of successive fear conditionings. These data also support the concept that HPC deactivation may be involved in fear learning sensitization and fear return in PTSD patients.

The genome-wide landscape of DNA methylation and hydroxymethylation in response to sleep deprivation impacts on synaptic plasticity genes.

Sleep is critical for normal brain function and mental health. However, the molecular mechanisms mediating the impact of sleep loss on both cognition and the sleep electroencephalogram remain mostly unknown. Acute sleep loss impacts brain gene expression broadly. These data contributed to current hypotheses regarding the role for sleep in metabolism, synaptic plasticity and neuroprotection. These changes in gene expression likely underlie increased sleep intensity following sleep deprivation (SD). Here we tested the hypothesis that epigenetic mechanisms coordinate the gene expression response driven by SD. We found that SD altered the cortical genome-wide distribution of two major epigenetic marks: DNA methylation and hydroxymethylation. DNA methylation differences were enriched in gene pathways involved in neuritogenesis and synaptic plasticity, whereas large changes (>4000 sites) in hydroxymethylation where observed in genes linked to cytoskeleton, signaling and neurotransmission, which closely matches SD-dependent changes in the transcriptome. Moreover, this epigenetic remodeling applied to elements previously linked to sleep need (for example, Arc and Egr1) and synaptic partners of Neuroligin-1 (Nlgn1; for example, Dlg4, Nrxn1 and Nlgn3), which we recently identified as a regulator of sleep intensity following SD. We show here that Nlgn1 mutant mice display an enhanced slow-wave slope during non-rapid eye movement sleep following SD but this mutation does not affect SD-dependent changes in gene expression, suggesting that the Nlgn pathway acts downstream to mechanisms triggering gene expression changes in SD. These data reveal that acute SD reprograms the epigenetic landscape, providing a unique molecular route by which sleep can impact brain function and health.