Biomedical subjects

Roelof A Hut

Publications and source records attributed to Roelof A Hut.

8 recordsLinked to original sources

PubMed2006

Characterizing a mammalian circannual pacemaker.

Many species express endogenous cycles in physiology and behavior that allow anticipation of the seasons. The anatomical and cellular bases of these circannual rhythms have not been defined. Here, we provide strong evidence using an in vivo Soay sheep model that the circannual regulation of prolactin secretion, and its associated biology, derive from a pituitary-based timing mechanism. Circannual rhythm generation is seen as the product of the interaction between melatonin-regulated timer cells and adjacent prolactin-secreting cells, which together function as an intrapituitary "pacemaker-slave" timer system. These new insights open the way for a molecular analysis of long-term timing mechanisms.

Animals↗

PubMed2006

Immunohistochemical evidence of a melanopsin cone in human retina.

PURPOSE: Melanopsin, expressed in a subset of intrinsically photosensitive ganglion cells that project to the suprachiasmatic nucleus (SCN), is involved in the photic entrainment of circadian rhythms and other non-image-forming functions (pupil light reflex, masking, acute heart rate response, and alertness). Melanopsin has recently been shown to be a "bireactive" photopigment that functions as a photosensory opsin using 11-cis retinaldehyde as a chromophore and has intrinsic photoisomerase activity. Melanopsin is widely distributed in the retina of vertebrates and, depending on the species, is expressed in ganglion, amacrine, horizontal, and photoreceptor cells. The present study was conducted to determine the distribution of this opsin in the human retina. METHODS: Human donor eyes were obtained from donors and fixed shortly after death. Immunohistochemistry was used to determine melanopsin expression in the retinas of three donors. The possible coexpression of this photopigment with other opsins was studied by double-labeling immunocytochemistry and confocal analysis. RESULTS: In addition to the expected labeling in ganglion cells of the inner retinal layers, an unexpected finding showed melanopsin-immunopositive label in the outer segments of cones that did not coexpress other known opsins. These melanopsin-expressing cones are extremely sparse (5-25 cones/mm2; 0.1%-0.5% of the entire cone population) and are located in the peripheral retina. CONCLUSIONS: The presence of melanopsin in human cones suggests image and non-image-forming roles in visual responses at both the cone input and ganglion cell output stages and their involvement in a broad spectrum of irradiance detection functions in the visual system.

Adult↗

PubMed2006

Transcriptional profiling in the adrenal gland reveals circadian regulation of hormone biosynthesis genes and nucleosome assembly genes.

The master circadian pacemaker of the suprachiasmatic nuclei coordinates behavioral and physiological rhythms via synchronization of subordinate peripheral oscillators in the central nervous system and organs throughout the body. Among these organs, the adrenal glands hold a prime position because of their regulatory influence on numerous physiological functions via rhythmic secretion of catecholamines and corticoid hormones into the bloodstream. In this report, the authors perform whole genome microarray hybridization to characterize the circadian transcriptome of the murine adrenal. They show that ~5% of the mouse genome is under circadian control in this gland. Using gene ontology analysis, they identify classes of transcripts that may synchronize adrenal hormone production. The authors' expression profiling also revealed that multiple histone genes implicated in either DNA replication or transcriptional regulation are clock controlled, suggesting a novel way by which the circadian clock may regulate the chromatin state.

Adrenal Glands↗

PubMed2004

Differential regulation of glomerular and interstitial endothelial nitric oxide synthase expression in the kidney of hibernating ground squirrel.

Hibernating animals transiently reduce renal function during their hypothermic periods (torpor), while completely restoring it during their periodical rewarming to euthermia (arousal). Moreover, structural integrity of the kidney is preserved throughout the hibernation. Nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) is a crucial vasodilatory mediator and a protective factor in the kidney. We investigated renal NOS expression in hibernating European ground squirrels after 1 day and 7 days of torpor (torpor short, TS, and torpor long, TL, respectively), at 1.5 and at 10 h of rewarming (arousal short, AS, and arousal long, AL, respectively), and in continuously euthermic animals after hibernation (EU). For that purpose, we performed NOS activity assay, immunohistochemistry and real-time PCR analysis. Immunohistochemistry revealed a decreased glomerular eNOS expression in hibernating animals (TS, TL, AS, and AL) compared to non-hibernating animals (EU, p < 0.05), whereas no difference was found in the expression of interstitial eNOS. Expression of iNOS and nNOS did not differ between all groups. The reduced glomerular eNOS was associated with a significantly lower eNOS mRNA levels and NOS activity of whole kidney during torpor and arousal (TS, TL, AS, and AL) compared to EU. In all methods used, torpid and aroused squirrels did not differ. These results demonstrate differential regulation of eNOS in glomeruli and interstitium of hibernating animals, which is unaffected during arousal. The differential regulation of eNOS may serve to reduce ultrafiltration without jeopardizing tubular structures during hibernation.

Animals↗

PubMed2004

Seasonal variation in daily activity patterns of free-ranging European ground squirrels (Spermophilus citellus).

Daily aboveground activity of European ground squirrels (Spermophilus citellus) in their natural habitat was recorded with a visual scanning procedure during the active seasons of 1992 and 1993. Activity patterns were analyzed with respect to time of year and to the animal's reproductive state. Aboveground activity started on average 3.9 h (SD 0.6 h, n = 37 days) after civil twilight at dawn and ended on average 3.2 h (SD 0.9 h, n = 37 days) before civil twilight at dusk. Between onset and offset of activity, 54% was spent aboveground, of which 73% was spent foraging. Activity patterns were influenced by photoperiod, rainfall, and by reproductive state. During mating, reproductively active males started activity earlier than females and reproductively inactive males. For females, time spent foraging was high during lactation. The midpoint of daily activity was at 12:16 h (SD 0.37 h, n = 37 days). Activity patterns of European ground squirrels thus appear robustly positioned in the middle of the photoperiod.

Animals↗

PubMed2003

Reversible paired helical filament-like phosphorylation of tau is an adaptive process associated with neuronal plasticity in hibernating animals.

Neurofibrillary pathology [paired helical filaments (PHFs)] formed by the microtubule-associated protein tau in a hyperphosphorylated form is a major hallmark of Alzheimer's disease and related disorders. The process of tau phosphorylation, thought to be of critical importance for PHF formation, and its potential link to neurodegeneration, however, is not understood very well, mostly because of the lack of a physiological in vivo model of PHF-like tau phosphorylation. Here we describe the formation of highly phosphorylated tau, containing a number of PHF-like epitopes in torpor during hibernation. PHF-like phosphorylation of tau was not associated with fibril formation and was fully reversible after arousal. Distribution of PHF-like tau followed a consistent pattern, being most intense in the entorhinal cortex, hippocampus, and isocortical areas. Within the hippocampus, a particularly high labeling was seen in CA3 pyramidal cells. Somewhat lesser reactivity was present in CA1 neurons while dentate gyrus granule cells were not reactive. Formation of PHF-like tau in CA3 neurons was paralleled by the regression of synaptic contacts of the mossy fiber system terminating on CA3 apical dendrites. Mossy fiber afferentation was re-established during arousal, concomitantly with the decrease of PHF-like tau in CA3 neurons. These findings implicate an essential link between neuronal plasticity and PHF-like phosphorylation of tau. The repeated formation and degradation of PHF-like tau might, thus, represent a physiological mechanism not necessarily associated with pathological effects. Hibernation will, therefore, be a valuable model to study the regulation of PHF-like tau-phosphorylation and its cell biological sequelae under physiological in vivo conditions.

Adaptation, Physiological↗

PubMed2003

Hippocampal synaptophysin immunoreactivity is reduced during natural hypothermia in ground squirrels.

Natural hypothermia during hibernation results in physiological and behavioral deficits. These changes may be traced at the level of hippocampal signal transduction. We investigated synaptophysin immunoreactivity (SYN-ir) in the hippocampus after short and long periods of hypothermia and short and long periods of euthermy in hibernating ground squirrels. SYN-ir in the stratum lucidum of the hippocampus was transiently reduced during natural hypothermia. Natural hypothermia thus reduces synaptic efficacy. This may play a role in the reduced neuronal connectivity of CA3 pyramidal cell dendrites observed in hibernating ground squirrels.

Animals↗

PubMed2002

Normalization of aortic function during arousal episodes in the hibernating ground squirrel.

Hypothermia is commonly used to restrict organ damage during preservation of tissue, but does not offer complete protection. Organ damage after reperfusion/rewarming is amongst others caused by an impairment of vascular properties, particularly endothelium-dependent vasodilatation. We hypothesized that hibernating small animals, which frequently cycle through periods of deep cooling (torpor) and full rewarming (arousal), employ specific mechanisms to preserve vascular function after cooling and reperfusion. Therefore we measured contraction of aortic tissue of hibernating European ground squirrels after 24 h and 7 days of torpor, arousal (1.5 h) and in non-hibernating animals. To assess the role of nitric oxide (NO), experiments were performed in the absence and presence of the NO-synthesis inhibitor, L-NMMA (10(-4) M). Maximum contraction to phenylephrine and angiotensin II was doubled in 7-days torpid animals without a shift in EC50, compared to the other 3 groups. Maximum contraction to KCl was doubled in 7-days torpid animals compared to the arousal group and non-hibernating animals. Relaxation to acetylcholine (ACh) and sodium nitrite in phenylephrine precontracted rings did not differ between groups. In the presence of L-NMMA, the maximum of concentration-response curves for all three vasoconstrictors was increased by about 30% in the arousal group, but unaffected in other groups. L-NMMA completely inhibited ACh-induced relaxation in 24-h torpid animals and non-hibernating animals, but only partially in 7-days torpid animals and in the arousal group. From this we conclude that vascular adaptation proceeds during torpor. Further, increased contractility of aortic tissue during long torpor returns to normal within 1.5 hours of arousal, which is associated with an increased basal NO synthesis. In addition, involvement of NO in agonist-mediated relaxation differs between the various stages of hibernation.Thus, hibernating animals have effectively developed mechanisms to preserve vascular function after cooling and rewarming.

Animals↗