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Bisschop P.H.,University of Amsterdam | Dekker M.J.H.J.,Erasmus Medical Center | Osterthun W.,University of Amsterdam | Kwakkel J.,University of Amsterdam | And 8 more authors.
Journal of Neuroendocrinology | Year: 2013

The hypothalamus is a major target for glucocorticoids and a key structure for hypothalamic-pituitary-adrenal (HPA) axis setpoint regulation. The enzyme 11β hydroxysteroid dehydrogenase type 1 (11βHSD1) modulates glucocorticoid signalling in various tissues at the prereceptor level by converting biologically inactive cortisone to its active form cortisol. The present study aimed to assess 11βHSD1 expression in the human hypothalamus. We studied 11βHSD1 expression in five frozen and four formalin-fixed, paraffin-embedded human hypothalami (obtained from the Netherlands Brain Bank) by the polymerase chain reaction and immunocytochemistry, respectively. 11βHSD1 mRNA was expressed in the area of the suprachiasmatic nucleus, which is the biological clock of the brain, in the supraoptic nucleus and paraventricular nucleus (PVN), and in the infundibular nucleus, which is the human homologue of the rodent arcuate nucleus. 11βHSD1 was detected by immunocytochemistry in the same nuclei. In the PVN, neuronal 11βHSD1 immunoreactivity colocalised with corticotrophin-releasing hormone (CRH), arginine vasopressin and oxytocin, as shown by dual fluorescence staining. Our data demonstrate that 11βHSD1 is widely expressed in the human hypothalamus. Its colocalisation with CRH in the PVN suggests a role in modulation of glucocorticoid feedback of the HPA axis, whereas the expression of 11βHSD1 in additional and functionally diverse hypothalamic nuclei points to a role for the enzyme in the regulation of metabolism, appetite and circadian rhythms. © 2013 British Society for Neuroendocrinology.

Luik A.I.,Erasmus Medical Center | Zuurbier L.A.,Erasmus Medical Center | Hofman A.,Erasmus Medical Center | Van Someren E.J.W.,Institute of the Netherlands Royal Academy of Arts and science | And 4 more authors.
Sleep Medicine | Year: 2015

Background: Cognitive functioning changes with age, sleep, and the circadian rhythm. We investigated whether these factors are independently associated with different cognitive domains assessed in middle-aged and elderly persons. Methods: In 1723 middle-aged and elderly persons (age 62 ± 9.4 years, mean ± standard deviation, SD) of the Rotterdam Study, we collected actigraphy recordings of on average 138 h. Actigraphy was used to quantify 24-h rhythms by calculating the stability of the rhythm over days and the fragmentation of the rhythm. Sleep parameters including total sleep time, sleep-onset latency, and wake after sleep onset were also estimated from actigraphy. Cognitive functioning was assessed with the word learning test (WLT), word fluency test (WFT), letter digit substitution task (LDST), and Stroop color word test (Stroop). Results: Persons with less stable 24-h rhythms performed worse on the LDST (. B = 0.42 per SD increase, p = 0.004) and the Stroop interference trial (. B = -1.04 per SD increase, p = 0.003) after full adjustment. Similarly, persons with more fragmented rhythms performed worse on the LDST (. B = -0.47 per SD increase, p = 0.002) and the Stroop (. B = 1.47 per SD increase, p <. 0.001). By contrast, longer observed sleep-onset latencies were related to worse performance on the WLT delayed recall (. B = -0.19 per SD increase, p = 0.027) and the WFT (. B = -0.45 per SD increase, p = 0.007). Conclusions: Disturbances of sleep and the 24-h activity rhythm were independently related to cognition; while persons with longer sleep-onset latencies had worse performance on memory and verbal tasks, persons with 24-h rhythm disturbances performed less on executive functioning and perceptual speed tasks. © 2015 Elsevier B.V.

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