Heat shock proteins Hsp27 and Hsp32 localize to synaptic sites in the rat cerebellum following hyperthermia

Stressful stimuli activate the heat shock (stress) response in which a set of heat shock proteins (hsps) is induced, which play roles in cellular repair and protective mechanisms. Most studies in the mammalian nervous system have focused on Hsp70, however, the present investigation targets other members of the induced set, namely Hsp27 and Hsp32. In response to hyperthermia, these hsps are strongly induced in Bergmann glial cells in the rat brain and transported into their radial fibers, which project into the `synaptic-enriched' molecular layer of the cerebellum. Using subcellular fractionation and immunoelectron microscopy, hyperthermia-induced Hsp27 and Hsp32 were detected in synaptic elements and in perisynaptic glial processes. These results suggest that stress-induced Hsp27 and Hsp32 may contribute to repair and protective mechanisms at the synapse

Suprachiasmatic nucleus-dependent and independent outputs driving rhythmic activity in hypothalamic and thalamic neurons

From Springer Nature via Jisc Publications RouterHistory: received 2020-05-29, registration 2020-09-17, accepted 2020-09-17, pub-electronic 2020-09-30, online 2020-09-30, collection 2020-12Publication status: PublishedFunder: Biotechnology and Biological Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/N007115/1Abstract: Background: Daily variations in mammalian physiology are under control of a central clock in the suprachiasmatic nucleus (SCN). SCN timing signals are essential for coordinating cellular clocks and associated circadian variations in cell and tissue function across the body; however, direct SCN projections primarily target a restricted set of hypothalamic and thalamic nuclei involved in physiological and behavioural control. The role of the SCN in driving rhythmic activity in these targets remains largely unclear. Here, we address this issue via multielectrode recording and manipulations of SCN output in adult mouse brain slices. Results: Electrical stimulation identifies cells across the midline hypothalamus and ventral thalamus that receive inhibitory input from the SCN and/or excitatory input from the retina. Optogenetic manipulations confirm that SCN outputs arise from both VIP and, more frequently, non-VIP expressing cells and that both SCN and retinal projections almost exclusively target GABAergic downstream neurons. The majority of midline hypothalamic and ventral thalamic neurons exhibit circadian variation in firing and those receiving inhibitory SCN projections consistently exhibit peak activity during epochs when SCN output is low. Physical removal of the SCN confirms that neuronal rhythms in ~ 20% of the recorded neurons rely on central clock input but also reveals many neurons that can express circadian variation in firing independent of any SCN input. Conclusions: We identify cell populations across the midline hypothalamus and ventral thalamus exhibiting SCN-dependent and independent rhythms in neural activity, providing new insight into the mechanisms by which the circadian system generates daily physiological rhythms

Sleep and cognitive performance:cross-sectional associations from the UK Biobank

Objective: The relationship between insomnia symptoms and cognitive performance is unclear, particularly at the population level. We conducted the largest examination of this association to date through analysis of the UK Biobank, a large population-based sample of adults aged 40-69 yrs. We also sought to determine associations between cognitive performance and self-reported chronotype, sleep medication use, and sleep duration. Methods: This cross-sectional, population-based study involved 477,529 participants, comprising 133,314 with frequent insomnia symptoms (age: 57.4 ± 7.7 yrs; 62.1% female) and 344,215 controls without (age: 56.1 ± 8.2 yrs; 52.0% female). Cognitive performance was assessed through a touchscreen test battery probing reasoning, basic reaction time, numeric memory, visual memory and prospective memory. Adjusted models included relevant demographic, clinical and sleep variables. Results: Frequent insomnia symptoms were associated with cognitive impairment in unadjusted models, however these effects were reversed after full adjustment, leaving those with frequent insomnia symptoms showing statistically better cognitive performance over those without. Relative to intermediate chronotype, evening chronotype was associated with superior task performance, while morning chronotype was associated with the poorest performance. Sleep medication use and both long (>9hrs) and short (<7hrs) sleep duration were associated with impaired performance. Conclusions: Our results suggest that after adjustment for potential confounding variables, frequent insomnia symptoms may be associated with a small statistical advantage, which is unlikely to be clinically meaningful, on simple neurocognitive tasks. Further work is required to examine mechanistic underpinnings of an apparent evening chronotype advantage in cognitive performance, as well as impairment associated with morning chronotype, sleep medication use, and sleep duration extremes

Molecular Hydrogen in the Damped Ly alpha Absorber of Q1331+170

We used HST/STIS to obtain the spectrum of molecular hydrogen associated with the damped Ly$\alpha$ system at $z_{\rm abs}=1.7765$ toward the quasar Q1331+170 at $z_{\rm em}=2.084$. Strong ${\rm H}_2$ absorption was detected, with a total ${\rm H}_2$ column density of $N({\rm H}_2)=(4.45\pm 0.36)\times 10^{19} {\rm cm^{-2}}$.The molecular hydrogen fraction is $f_{{\rm H}_2}=\frac{2N_{\rm H_2}}{N_{\rm HI}+2N_{\rm H_2}}=(5.6\pm 0.7)$, which is the greatest value reported so far in any redshifted damped Ly$\alpha$ system. This results from the combined effect of a relatively high dust-to-gas ratio, a low gas temperature, and an extremely low ambient UV radiation field. Based on the observed population of $J$ states, we estimate the photo-absorption rate to be $R_{\rm abs}=(7.6\pm 2.4)\times 10^{-13} {\rm s^{-1}}$, corresponding to a local UV radiation field of $J(1000{\rm \AA})\approx 2.1\times 10^{-3} J_{1000{\rm \AA},\odot}$, where $J_{1000{\rm \AA},\odot}$ is the UV intensity at $1000 \AA$ in the solar neighborhood. This is comparable with the metagalactic UV background intensity at this redshift, and implies an extremely low star formation rate in the absorber's environment. The observed CO-to-H$_2$ column density ratio is $\frac{N_{\rm CO}}{N_{\rm H_2}}<2.5\times 10^{-7}$, which is similar to the value measured for diffuse molecular clouds in the Galactic ISM. Finally, applying the inferred physical conditions to the observed C I fine structure excitation (Songaila {\it et al.} 1994), we estimate the cosmic microwave background temperature to be $T_{\rm CMB}=(7.2\pm 0.8) {\rm K}$ at $z=1.77654$, consistent with the predicted value of $7.566 {\rm K}$ from the standard cosmology.Comment: Accepted for publication, Astrophysical Journal. Abstract abbreviate

Pressure Support vs. Thermal Broadening in the Lyman-alpha Forest II: Effects of the Equation of State on Transverse Structure

We examine the impact of gas pressure on the transverse coherence of high-redshift (2 <= z <= 4) Lyman-alpha forest absorption along neighboring lines of sight that probe the gas Jeans scale (projected separation Delta r <= 500 kpc/h comoving; angular separation Delta theta <= 30"). We compare predictions from two smoothed particle hydrodynamics (SPH) simulations that have different photoionization heating rates and thus different temperature-density relations in the intergalactic medium (IGM). We also compare spectra computed from the gas distributions to those computed from the pressureless dark matter. The coherence along neighboring sightlines is markedly higher for the hotter, higher pressure simulation, and lower for the dark matter spectra. We quantify this coherence using the flux cross-correlation function and the conditional distribution of flux decrements as a function of transverse and line-of-sight (velocity) separation. Sightlines separated by Delta theta <= 15" are ideal for probing this transverse coherence. Higher pressure decreases the redshift-space anisotropy of the flux correlation function, while higher thermal broadening increases the anisotropy. In contrast to the longitudinal (line-of-sight) structure of the Lya forest, the transverse structure on these scales is dominated by pressure effects rather than thermal broadening. With the rapid recent growth in the number of known close quasar pairs, paired line-of-sight observations offer a promising new route to probe the IGM temperature-density relation and test the unexpectedly high temperatures that have been inferred from single sightline analyses.Comment: 11 figures, submitted to MNRA

Sleep homeostasis during daytime food entrainment in mice

24h rhythms of physiology and behavior are driven by the environment and an internal endogenous timing system. Daily restricted feeding (RF) in nocturnal rodents during their inactive phase initiates food anticipatory activity (FAA) and a reorganisation of the typical 24h sleep-wake structure. Here, we investigate the effects of daytime feeding, where food access was restricted to 4h during the light period ZT4-8 (Zeitgeber time; ZT0 is lights on), on sleep-wake architecture and sleep homeostasis in mice. Following 10 days of RF, mice were returned to ad libitum feeding. To mimic the spontaneous wakefulness associated with FAA and daytime feeding, mice were then sleep deprived between ZT3-6. While the amount of wake increased during FAA and subsequent feeding, total wake time over 24h remained stable as the loss of sleep in the light phase was compensated for by an increase in sleep in the dark phase. Interestingly, sleep which followed spontaneous wake episodes during the dark period and the extended period of wake associated with FAA, exhibited lower levels of slow-wave activity (SWA) when compared to baseline or after sleep deprivation, despite a similar duration of waking. This suggests an evolutionary mechanism of reducing sleep drive during negative energy balance to enable greater arousal for food seeking behaviors. However, the total amount of sleep and SWA accumulated during the 24h was similar between baseline and RF. In summary, our study suggests that despite substantial changes in the daily distribution and quality of wake induced by RF, sleep homeostasis is maintained.</p

Identification of Melatonin-Regulated Genes in the Ovine Pituitary Pars Tuberalis, a Target Site for Seasonal Hormone Control

The pars tuberalis (PT) of the pituitary gland expresses a high density of melatonin (MEL) receptors and is believed to regulate seasonal physiology by decoding changes in nocturnal melatonin secretion. Circadian clock genes are known to be expressed in the PT in response to the decline (Per1) and onset (Cry1) of MEL secretion, but to date little is known of other molecular changes in this key MEL target site. To identify transcriptional pathways that may be involved in the diurnal and photoperiod-transduction mechanism, we performed a whole genome transcriptome analysis using PT RNA isolated from sheep culled at three time points over the 24-h cycle under either long or short photoperiods. Our results reveal 153 transcripts where expression differs between photoperiods at the light-dark transition and 54 transcripts where expression level was more globally altered by photoperiod (all time points combined). Cry1 induction at night was associated with up-regulation of genes coding for NeuroD1 (neurogenic differentiation factor 1), Pbef / Nampt (nicotinamide phosphoribosyltransferase) , Hif1α (hypoxia-inducible factor-1α), and Kcnq5 (K channel) and down-regulation of Rorβ, a key clock gene regulator. Using in situ hybridization, we confirmed day-night differences in expression for Pbef / Nampt, NeuroD1, and Rorβ in the PT. Treatment of sheep with MEL increased PT expression for Cry1, Pbef / Nampt, NeuroD1, and Hif1α, but not Kcnq5. Our data thus reveal a cluster of Cry1-associated genes that are acutely responsive to MEL and novel transcriptional pathways involved in MEL action in the PT