Dopamine Transporter Regulation during Four Nights of REM Sleep Deprivation Followed by Recovery – An in vivo Molecular Imaging Study in Humans

Objectives:

To assess the influence of total or selective REM sleep deprivation on the dopamine transporter (DAT) densities and sleep patterns of healthy volunteers.

Design:

Prospective study.

Setting:

Evaluation of polysomnography recordings and DAT density after 4 nights of selective REM sleep deprivation followed by 3 nights of sleep recovery compared to a control group and a group that was subjected to 2 nights of total sleep deprivation. Single positron emission computed tomography and [^99mTc]TRODAT-1 were used to assess the cerebral DAT density in the striatum at baseline, after REM sleep deprivation and total sleep deprivation as well as after sleep recovery. Blood was collected daily to examine prolactin and estradiol levels, which were correlated with dopaminergic activity.

Patients or Participants:

Thirty healthy male volunteers ranging from 19 to 29 years of age were randomly assigned to one of three experimental groups after giving written informed consent (10 non-sleep deprived, 10 total sleep deprived, and 10 REM sleep deprived).

Measurements and Results:

Four nights of REM sleep deprivation and 2 nights of total sleep deprivation induced distinct and heterogeneous patterns of sleep recovery. No significant modulation of DAT availability was observed within groups. In the recovery nights, changes in cortisol, prolactin and estradiol concentrations were significantly correlated with specific sleep stages in the total and REM sleep deprived groups. In addition, DAT density was positively correlated with estradiol concentration and inversely associated with SWS latency only after total sleep deprivation.

Conclusion:

Our study demonstrates that although sleep deprivation did not promote significant alterations in DAT density within the striatum, there were significant correlations among transporter availability, hormonal concentrations and sleep parameters.

Citation:

Martins, RCS; Andersen ML; Garbuio SA; Bittencourt LR: Guindalini C; Shih MC; Hoexter MQ; Bressan RA; Castiglioni MLV; Tufik S. Dopamine transporter regulation during four nights of REM sleep deprivation followed by recovery – an in vivo molecular imaging study in humans. SLEEP 2010;33(2):243-251.     

Special Editorial: Open science and the Journal of Child Psychology & Psychiatry – next steps?

The JCPP works at the cutting edge of clinical science to publish ground‐breaking research across the full range of topics in the field of child psychology and psychiatry. As JCPP editors, who are also active researchers in our own right, we are conscious of the threat posed to our field by what has come to be known as the reproducibility crisis ‐ the fact that many published findings, initially trumpeted as important developments in the field, cannot be replicated and are therefore likely to be spurious (Nature Human Behaviour, 1, 2017, 21). The JCPP is conscious of its responsibility to play its part in addressing this issue as best it can. The roots of the problem are complex and its causes multifaceted. As one part of its response, the JCPP embraces the principles of open science and encourage preregistration of study protocols. Furthermore, we are working towards implementing new systems to promote preregistration with the hope of increasing scientific transparency and accountability and reducing the risks of selective reporting and posthoc rationalisation of findings (Journal of Child Psychology & Psychiatry, 59, 2018, 1).     

O等位基因引起ABO基因型与表现型定型差异

保证输血时血清学方面的安全,首要的是对受血者与献血者ABO血型定型,血清学检查通常分两个步骤.正定型通常使用鼠源单克隆抗体检测红细胞表面是否存在A或B抗原.互补的实验即反定型,利用当红细胞上缺乏A或B抗原时,人群可天然产生相对应的抗体的原理,检测血清中是否存在抗-A或者抗-B抗体.确定了受血者红细胞表面的ABO抗原以及血浆中的抗体,便能确定血型,为其提供相合的血液.     

Expression of Stem Cell Markers in the Human Fetal Kidney

In the human fetal kidney (HFK) self-renewing stem cells residing in the metanephric mesenchyme (MM)/blastema are induced to form all cell types of the nephron till 34^th week of gestation. Definition of useful markers is crucial for the identification of HFK stem cells. Because wilms' tumor, a pediatric renal cancer, initiates from retention of renal stem cells, we hypothesized that surface antigens previously up-regulated in microarrays of both HFK and blastema-enriched stem-like wilms' tumor xenografts (NCAM, ACVRIIB, DLK1/PREF, GPR39, FZD7, FZD2, NTRK2) are likely to be relevant markers. Comprehensive profiling of these putative and of additional stem cell markers (CD34, CD133, c-Kit, CD90, CD105, CD24) in mid-gestation HFK was performed using immunostaining and FACS in conjunction with EpCAM, an epithelial surface marker that is absent from the MM and increases along nephron differentiation and hence can be separated into negative, dim or bright fractions. No marker was specifically localized to the MM. Nevertheless, FZD7 and NTRK2 were preferentially localized to the MM and emerging tubules (<10% of HFK cells) and were mostly present within the EpCAM^neg and EpCAM^dim fractions, indicating putative stem/progenitor markers. In contrast, single markers such as CD24 and CD133 as well as double-positive CD24⁺CD133⁺ cells comprise >50% of HFK cells and predominantly co-express EpCAM^bright, indicating they are mostly markers of differentiation. Furthermore, localization of NCAM exclusively in the MM and in its nephron progenitor derivatives but also in stroma and the expression pattern of significantly elevated renal stem/progenitor genes Six2, Wt1, Cited1, and Sall1 in NCAM⁺EpCAM^- and to a lesser extent in NCAM⁺EpCAM⁺ fractions confirmed regional identity of cells and assisted us in pinpointing the presence of subpopulations that are putative MM-derived progenitor cells (NCAM⁺EpCAM⁺FZD7⁺), MM stem cells (NCAM⁺EpCAM^-FZD7⁺) or both (NCAM⁺FZD7⁺). These results and concepts provide a framework for developing cell selection strategies for human renal cell-based therapies.