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Hol E.M.,University Utrecht | Hol E.M.,Institute of the Royal Netherlands Academy of Arts and science | Hol E.M.,University of Amsterdam
Frontiers in Molecular Neuroscience | Year: 2014

The ubiquitin proteasome system (UPS) is crucial for intracellular protein homeostasis and for degradation of aberrant and damaged proteins. The accumulation of ubiquitinated proteins is a hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's, Parkinson's, and Huntington's disease, leading to the hypothesis that proteasomal impairment is contributing to these diseases. So far, most research related to the UPS in neurodegenerative diseases has been focused on neurons, while glial cells have been largely disregarded in this respect. However, glial cells are essential for proper neuronal function and adopt a reactive phenotype in neurodegenerative diseases, thereby contributing to an inflammatory response. This process is called reactive gliosis, which in turn affects UPS function in glial cells. In many neurodegenerative diseases, mostly neurons show accumulation and aggregation of ubiquitinated proteins, suggesting that glial cells may be better equipped to maintain proper protein homeostasis. During an inflammatory reaction, the immunoproteasome is induced in glia, which may contribute to a more efficient degradation of disease-related proteins. Here we review the role of the UPS in glial cells in various neurodegenerative diseases, and we discuss how studying glial cell function might provide essential information in unraveling mechanisms of neurodegenerative diseases. © 2014 Jansen, Reits and Hol.

Mantione M.,University of Amsterdam | Nieman D.H.,University of Amsterdam | Figee M.,University of Amsterdam | Denys D.,University of Amsterdam | Denys D.,Institute of the Royal Netherlands Academy of Arts and science
Psychological Medicine | Year: 2014

Background. Deep brain stimulation (DBS) is a promising new treatment for patients with treatment-refractory obsessive-compulsive disorder (OCD). However, since most DBS patients only show a partial response, the treatment still needs to be improved. In this study we hypothesized that cognitive-behavioural therapy (CBT) could optimize the post-operative management in DBS and we evaluated the efficacy of CBT as augmentation to DBS targeted at the nucleus accumbens.Method. A total of 16 patients with treatment-refractory OCD were treated with DBS targeted at the nucleus accumbens. After stabilization of decline in OCD symptoms, a standardized 24-week CBT treatment programme was added to DBS in an open-phase trial of 8 months. Changes in obsessive-compulsive, anxiety and depressive symptoms were evaluated using the Yale-Brown Obsessive Compulsive Scale, Hamilton Anxiety Scale and Hamilton Rating Scale for Depression.Results. Following the addition of CBT to DBS, a significant decrease in obsessive-compulsive symptoms was observed, but not in anxiety and depressive symptoms. In a subsequent double-blind phase, in which stimulation was discontinued, OCD symptoms returned to baseline (relapse) and anxiety and depressive symptoms worsened (rebound) compared with baseline.Conclusions. The results of this explorative study suggest that a combined treatment of accumbens DBS and CBT may be optimal for improving obsessive-compulsive symptoms in treatment-refractory OCD. However, a subsequent randomized controlled trial is necessary to draw firm conclusions. It seems that DBS results in affective changes that may be required to enable response prevention in CBT. This may indicate that DBS and CBT act as two complementary treatments. Copyright © 2014 Cambridge University Press.

Lucassen P.J.,University of Amsterdam | Pruessner J.,McGill University | Sousa N.,University of Minho | Sousa N.,ICVS 3Bs PT Government Associate Laboratory | And 5 more authors.
Acta Neuropathologica | Year: 2014

Environmental challenges are part of daily life for any individual. In fact, stress appears to be increasingly present in our modern, and demanding, industrialized society. Virtually every aspect of our body and brain can be influenced by stress and although its effects are partly mediated by powerful corticosteroid hormones that target the nervous system, relatively little is known about when, and how, the effects of stress shift from being beneficial and protective to becoming deleterious. Decades of stress research have provided valuable insights into whether stress can directly induce dysfunction and/or pathological alterations, which elements of stress exposure are responsible, and which structural substrates are involved. Using a broad definition of pathology, we here review the "neuropathology of stress" and focus on structural consequences of stress exposure for different regions of the rodent, primate and human brain. We discuss cytoarchitectural, neuropathological and structural plasticity measures as well as more recent neuroimaging techniques that allow direct monitoring of the spatiotemporal effects of stress and the role of different CNS structures in the regulation of the hypothalamic- pituitary-adrenal axis in human brain. We focus on the hypothalamus, hippocampus, amygdala, nucleus accumbens, prefrontal and orbitofrontal cortex, key brain regions that not only modulate emotions and cognition but also the response to stress itself, and discuss disorders like depression, post-traumatic stress disorder, Cushing syndrome and dementia. © 2013 Springer-Verlag Berlin Heidelberg.

Castilla-Marti M.,MIOS SA | Van Den Berg T.J.T.P.,Institute of the Royal Netherlands Academy of Arts and science | De Smet M.D.,MIOS SA
Retina | Year: 2015

Purpose: To evaluate the effect of vitreous floaters on intraocular straylight. Methods: Records of bilaterally phakic patients with unilateral complaint of floaters as the main symptom were identified from an electronic database. Patients who underwent straylight measurements on both affected and unaffected eyes using a C-Quant straylight meter were selected. Data were collected on age, sex, visual acuity, straylight measurements, and optical coherence tomography. The unaffected eye served as a control. Results: Fifteen cases were included (7 women and 8 men; mean age, 54.3 years; age range, 24-71 years). Visual acuity was not correlated with the complaint of floaters. Average straylight value in eyes with floaters was 1.426 log(s) (±0.23 SD) with a median value of 1.52 log(s). The mean value for fellow eyes was 1.275 (±0.23 SD) with a median of 1.25 log(s). The differences between both groups using a Wilcoxon matched-pair signed-rank test was statistically significant at P 0.0009. On optical coherence tomography, most patients had a confirmed or probable posterior vitreous detachment. However, in four patients, a posterior vitreous detachment was absent in the affected eyes. Vitreous floaters were inconsistently imaged by optical coherence tomography, with only a few patients presenting appreciable condensations close to the retinal surface. These were present in both affected and unaffected eyes. Conclusion: Intraocular straylight is significantly increased in eyes affected by floaters. No correlation was seen with vision or optical coherence tomography appearance. Straylight is an independent objective measure of visual perception that seems to be closely correlated to complaints expressed by patients experiencing floaters. Copyright © by Ophthaimac Communications Society, Inc.unauthorized Reproduction Of This Article Is Prohibited.

Naninck E.F.G.,University of Amsterdam | Naninck E.F.G.,Institute of the Royal Netherlands Academy of Arts and science | Lucassen P.J.,University of Amsterdam | Bakker J.,Institute of the Royal Netherlands Academy of Arts and science
Journal of Neuroendocrinology | Year: 2011

Depression is one of the most common, costly and severe psychopathologies worldwide. Its incidence, however, differs significantly between the sexes, and depression rates in women are twice those of men. Interestingly, this sex difference emerges during adolescence. Although the adolescent period is characterised by major physical and behavioural transformations, it is unclear why the incidence of depression increases so dramatically in girls during this otherwise generally healthy developmental period. Although psychological and environmental factors are also involved, we discuss the neuroendocrinological factors determining adolescent vulnerability to depression. In particular, we address the role of sex steroids in mood regulation, hypothalamic-pituitary-adrenal axis maturation and sexual differentiation of the brain, with a focus on hippocampal plasticity. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

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