Dick F Swaab

Netherlands Institute for Neuroscience, Amsterdamo, North Holland, Netherlands

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Publications (195)843.97 Total impact

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    ABSTRACT: Background The human hypothalamus contains the neuropeptide FF (NPFF) neurochemical network. Animal experiments demonstrated that NPFF is implicated in the central cardiovascular regulation. We therefore studied expression of this peptide in the hypothalamus of individuals who suffered from essential hypertension (n = 8) and died suddenly due to acute myocardial infarction (AMI), and compared to that of healthy individuals (controls) (n = 6) who died abruptly due to mechanical trauma of the chest.Methods The frozen right part of the hypothalamus was cut coronally into serial sections of 20 μm thickness, and each tenth section was stained immunohistochemically using antibody against NPFF. The central section through each hypothalamic nucleus was characterized by the highest intensity of NPFF immunostaining and thus was chosen for quantitative densitometry.ResultsIn hypertensive patients, the area occupied by NPFF immunostained neuronal elements in the central sections through the suprachiasmatic nucleus (SCh), paraventricular hypothalamic nucleus (Pa), bed nucleus of the stria terminalis (BST), perinuclear zone (PNZ) of the supraoptic nucleus (SON), dorso- (DMH), ventromedial (VMH) nuclei, and perifornical nucleus (PeF) was dramatically decreased compared to controls, ranging about six times less in the VMH to 15 times less in the central part of the BST (BSTC). The NPFF innervation of both nonstained neuronal profiles and microvasculature was extremely poor in hypertensive patients compared to control.Conclusions The decreased NPFF expression in the hypothalamus of hypertensive patients might be a cause of impairment of its interaction with other neurochemical systems, and thereby might be involved in the pathogenesis of the disease.
    Brain and Behavior. 04/2014;
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    ABSTRACT: The basis of gender differences in the prevalence and clinical progression of multiple sclerosis (MS) is not understood. Here, we identify gender-specific responses in steroid synthesis and signaling in the brains of MS patients as possible contributors to these differences. We investigated gene expression changes in these pathways and of inflammatory cytokines in MS lesions and normal-appearing white matter (NAWM) of male and female patients (n = 21) and control NAWM (n = 14) using quantitative polymerase chain reaction (25 MS lesions, 21 MS NAWM, and 14 control NAWM) and immunohistochemistry (3-4 sections per group). In MS lesions in males, there was local upregulation of aromatase (an enzyme involved in estrogen biosynthesis), estrogen receptor-β (ERβ), and tumor necrosis factor (TNF) mRNA; whereas in females, there was local upregulation of 3β-hydroxysteroid-dehydrogenase, a progesterone synthetic enzyme, and of progesterone receptor. Astrocytes in the rim and center of MS lesions were found to be the primary source of steroidogenic enzyme and receptor expression. Aromatase and ERα mRNA levels were positively correlated with that of TNF in primary cultures of human microglia and astrocytes; TNF caused increased ERα, suggesting that inflammatory signals stimulate estrogen signaling in this cell type. Together, these findings suggest that there are gender differences in the CNS of MS patients that may affect lesion pathogenesis, that is, in males, estrogen synthesis and signaling are induced; whereas in females, progestogen synthesis and signaling are induced. These differences may represent contributing factors to gender differences in the prevalence and course of MS.
    Journal of neuropathology and experimental neurology. 02/2014; 73(2):123-35.
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    ABSTRACT: Context: That serotonin plays a role in the regulation of feeding behavior and energy metabolism has been known for a long time. Serotonin transporters (SERT) play a crucial role in serotonin signaling by regulating its availability in the synaptic cleft. The neuroanatomy underlying serotonergic signaling in humans is largely unknown, and until now, SERT immunoreactivity in relation to body weight has not been investigated. Objective: To clarify the distribution of SERT immunoreactivity throughout the human hypothalamus and to compare SERT immunoreactivity in the infundibular nucleus (IFN), the human equivalent of the arcuate nucleus, in lean and overweight subjects. Design: First, we investigated the distribution of serotonin transporters (SERT) over the rostro-caudal axis of six post-mortem hypothalami by means of immunohistochemistry. Second, we estimated SERT immunoreactivity in the IFN of lean and overweight subjects. Lastly, double-labeling of SERT with Neuropeptide Y (NPY) and melanocortin cell populations was performed to further identify cells showing basket-like SERT staining. Results: SERT-immunoreactivity was ubiquitously expressed in fibers throughout the hypothalamus and was the strongest in the IFN. Immunoreactivity in the IFN was lower in overweight subjects (p = 0.036). Basket-like staining in the IFN was highly suggestive of synaptic innervation. A very small minority of cells showed SERT double labeling with NPY, agouti-related protein and α-melanocyte stimulating hormone. Conclusions: SERT is ubiquitously expressed in the human hypothalamus. Strong SERT immunoreactivity, was observed in the IFN a region important for appetite regulation, in combination with lower SERT immunoreactivity in the IFN of overweight and obese subjects, may point toward a role for hypothalamic SERT in human obesity.
    Frontiers in neuroscience. 01/2014; 8:106.
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    ABSTRACT: 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.
    Acta Neuropathologica 12/2013; · 9.73 Impact Factor
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    ABSTRACT: In Huntington disease (HD), hypothalamic neuropeptidergic systems are not equally affected at the peptide and mRNA levels. Because prohormone convertases (PCs) are critically involved in the conversion of propeptides into their active forms, we postulated that a decrease in PC expression may underlie these discrepancies. Therefore, we assessed the expression of PC1/3 and PC2 in the hypothalamic infundibular, suprachiasmatic, and paraventricular nuclei in postmortem tissues of HD patients and controls (n = 9, each) using immunocytochemistry and quantitative reverse transcription polymerase chain reaction. We also assessed PC1/3 and PC2 mRNA expression in the inferior frontal gyrus and colocalization of both PCs with corticotropin-releasing hormone and α-melanocyte-stimulating hormone. In HD patients, PC1/3 and PC2 expression was decreased in the hypothalamic infundibular (both p = 0.046) and paraventricular nuclei (p = 0.031 and p = 0.019). In the suprachiasmatic nucleus, PC1/3 and PC2 expressions were not different between HD and control cases; PC1/3 and PC2 mRNA levels in the inferior frontal gyrus were also not different. None of the PCs was colocalized with corticotropin-releasing hormone, whereas α-melanocyte-stimulating hormone showed colocalization with PC1/3 and PC2. These data suggest that defects in the processing of hypothalamic neuropeptides in HD may partially arise from decreased PC1/3 and PC2 expressions. These changes might contribute to selective neuropathology underlying various clinical manifestations and may provide novel therapeutic targets in HD patients.
    Journal of neuropathology and experimental neurology. 11/2013;
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    Dataset: Table 2
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    ABSTRACT: We also made available the raw data of the miRNA profiling obtained from the prefrontal cortex of Alzheimer's patients. This will allow data re-analysis of the nCounter experiment shown in the EMM paper.
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    Dataset: Table 1
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    ABSTRACT: In response to requests, we made available the raw data of the miRNA profiling obtained from the hippocampus of Alzheimer's patients. This will allow data re-analysis of the nCounter experiment shown in the EMM paper.
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    ABSTRACT: Alzheimer's disease (AD) is the most common form of dementia and characterized by deposition of amyloid-β (Aβ) plaques, neurofibrillary tangles consisting of hyperphosphorylated tau, atrophy, and progressive neurodegeneration. While the familial, early onset form of AD is known to be caused by specific mutations in genes encoding presenilin 1, presenilin 2, or amyloid-β protein precursor, the underlying mechanisms leading to the development of sporadic AD are still not known. The major risk factors are, however, aging and APOE ε4. Here we review the latest evidence for the involvement of malfunctioning insulin signaling, dysfunction of mitochondria-associated membranes, cerebrovascular changes, increased oxidative stress and free radical formation, DNA damage, disturbed energy metabolism, and synaptic dysfunction in early stages of AD. We focus on whether the changes in these processes precede or succeed the earliest symptoms in AD patients, i.e., minimal cognitive impairment. Since changes in Aβ processing are probably a key event in AD we also highlight the relationship of the above mentioned processes with the formation, secretion, aggregation, and toxicity of Aβ. Based on our literature findings we propose a model in which insulin dysfunction, pathological cerebrovascular changes, dysfunction of mitochondria-associated membranes, and/or synaptic changes are likely to interact with each other, thereby initiating and facilitating the development of AD pathology by accelerating the production and deposition of Aβ. Increased oxidative stress and free radical formation, DNA damage, disturbed energy metabolism, and synaptic loss follow these events, but still occur very early in AD.
    Journal of Alzheimer's disease: JAD 09/2013; · 4.17 Impact Factor
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    ABSTRACT: An overview of miRNAs altered in Alzheimer's disease (AD) was established by profiling the hippocampus of a cohort of 41 late-onset AD (LOAD) patients and 23 controls, showing deregulation of 35 miRNAs. Profiling of miRNAs in the prefrontal cortex of a second independent cohort of 49 patients grouped by Braak stages revealed 41 deregulated miRNAs. We focused on miR-132-3p which is strongly altered in both brain areas. Downregulation of this miRNA occurs already at Braak stages III and IV, before loss of neuron-specific miRNAs. Next-generation sequencing confirmed a strong decrease of miR-132-3p and of three family-related miRNAs encoded by the same miRNA cluster on chromosome 17. Deregulation of miR-132-3p in AD brain appears to occur mainly in neurons displaying Tau hyper-phosphorylation. We provide evidence that miR-132-3p may contribute to disease progression through aberrant regulation of mRNA targets in the Tau network. The transcription factor (TF) FOXO1a appears to be a key target of miR-132-3p in this pathway.
    EMBO Molecular Medicine 09/2013; · 7.80 Impact Factor
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    ABSTRACT: The prefrontal cortex shows structural and functional alterations in mood disorders. Retinoid signaling, brain-derived neurotrophic factor (BDNF), and its receptor TrkB are reported to be involved in depression. Here, we found that mRNA levels of key elements of retinoid signaling were significantly reduced in the postmortem dorsolateral prefrontal cortex/anterior cingulate cortex (ACC) from elderly depressed patients who did not die from suicide. Decreased mRNA levels of BDNF and TrkB isoforms were also found. Similar alterations were observed in rats subjected to chronic unpredictable mild stress. Along with neurons immunopositive for both retinoic acid receptor-α (RARα) and TrkB, a positive correlation between mRNA levels of the 2 receptors was found in the ACC of control subjects but not of depressed patients. In vitro studies showed that RARα was able to bind to and transactivate the TrkB promoter via a putative RA response element within the TrkB promoter. In conclusion, the retinoid and BDNF-TrkB signaling in the prefrontal cortex are compromised in mood disorders, and the transcriptional upregulation of TrkB by RARα provide a possible mechanism for their interaction. The retinoid signaling pathway that may activate TrkB expression will be an alternative novel target for BDNF-based antidepressant treatment.
    Cerebral Cortex 08/2013; · 6.83 Impact Factor
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    ABSTRACT: BACKGROUND: The pineal hormone melatonin regulates circadian rhythms, largely by feedback on the central biological clock of the brain, the hypothalamic suprachiasmatic nucleus (SCN). This feedback is mediated by the melatonin receptors, melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). The circadian system may play a role in the pathophysiology of mood disorders, and indeed, melatonin-receptor agonists are considered a potential therapy for depression. METHOD: In order to investigate melatonin receptors in the SCN during depression, and their relationship to the major neuropeptides in the SCN, vasopressin (AVP) and vasoactive intestinal peptide (VIP), we studied the SCN in 14 depressed patients (five major depression and nine bipolar disorder) and 14 matched controls by immunocytochemistry. RESULTS: We show here that hypothalamic MT2 receptor immunoreactivity was limited to SCN, the supraoptic nucleus and paraventricular nucleus. We found that numbers of MT1-immunoreactive (MT1-ir) cells and AVP and/or VIP-ir cells were increased in the central SCN in depression, but numbers of MT2-ir cells were not altered. Moreover, the number of MT1-ir cells, but not MT2-ir cells was negatively correlated with age at onset of depression, while positively correlated with disease duration. CONCLUSION AND LIMITATIONS: Although every post-mortem study has limitations, MT1 receptors appeared specifically increased in the SCN of depressed patients, and may increase during the course of the disease. These changes may be involved in the circadian disorders and contribute to the efficacy of MT agonists or melatonin in depression. Moreover, we suggest that melatonin receptor agonists for depression should be targeted towards the MT1 receptor selectively.
    Journal of affective disorders 01/2013; · 3.76 Impact Factor
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    ABSTRACT: BACKGROUND: Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter. It diminishes the activity of the hypothalamo-pituitary-adrenal (HPA) axis, which plays an important role in the pathogenesis of depression. The present study aimed at determining GABAergic input in the hypothalamic paraventricular nucleus (PVN) in depression and its correlation with the activity of corticotropin-releasing hormone (CRH) neurons. METHODS: The density of glutamic acid decarboxylase (GAD)(65/67)-immunoreactivity (ir) was quantified in the postmortem hypothalamic PVN of 9 major depressive (MDD) and 5 bipolar depressive (BD) patients, together with 12 matched controls, whose CRH-expressing neuron numbers had been determined in a previous study. RESULTS: There was a 43% significant reduction of the density of GAD(65/67)-ir in the PVN in MDD (P=0.028) and a 20% non-significant decrease in BD patients. In addition, there was a significant negative correlation between the density of GAD(65/67)-ir and the number of CRH-ir neurons in the PVN in the depression group (Rho=-0.527, P=0.032), but not in the control group. LIMITATIONS: The samples were relatively small and the depression group had used antidepressants. CONCLUSION: A diminished GABAergic input to the PVN may contribute to the activation of CRH-ir neurons in depression, most prominently in MDD, which provides a rationale for prescribing GABAergic agonists for these patients.
    Journal of affective disorders 01/2013; · 3.76 Impact Factor
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    ABSTRACT: The glucocorticoid receptor (GR) exerts numerous functions in the body and brain. In the brain, it has been implicated, amongst others, in feedback regulation of the hypothalamic-pituitary-adrenal axis, with potential deficits during aging and in depression. GRs are abundantly expressed in the hippocampus of rodent, except for the Ammon's horn (CA) 3 subregion. In rhesus monkey however, GR protein was largely absent from all hippocampal subregions, which prompted us to investigate its distribution in human hippocampus. After validation of antibody specificity, we investigated GRα protein distribution in the postmortem hippocampus of 26 human control subjects (1-98 years of age) and quantified changes with age and sex. In contrast to monkey, abundant GR-immunoreactivity was present in nuclei of almost all neurons of the hippocampal CA subfields and dentate gyrus (DG), although neurons of the CA3 subregion displayed lower levels of immunoreactivity. Colocalization with glial fibrillary acidic protein confirmed that GR was additionally expressed in approximately 50% of the astrocytes in the CA regions, with lower levels of colocalization (approximately 20%) in the DG. With increased age, GR expression remained stable in the CA regions in both sexes, whereas a significant negative correlation was found with age only in the DG of females. Thus, in contrast to the very low levels previously reported in monkey, GR protein is prominently expressed in human hippocampus, indicating that this region can form an important target for corticosteroid effects in human.
    Neurobiology of aging 01/2013; · 5.94 Impact Factor
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    ABSTRACT: The hypothalamus is a major target for glucocorticoids and key structure for hypothalamus-pituitary-adrenal (HPA) axis setpoint regulation. The enzyme 11beta 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 objective of our study was to assess 11βHSD1 expression in the human hypothalamus. We studied 11βHSD1 expression in n=5 frozen and n=4 formalin-fixed, paraffin embedded human hypothalami (obtained from the Netherlands Brain Bank) by PCR and immunocytochemistry, respectively. 11βHSD1 mRNA was expressed in the area of the suprachiasmatic nucleus (SCN), which is the biological clock of the brain, in the supraoptic and paraventricular nuclei (SON and PVN), in the infundibular nucleus (IFN), 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 (AVP) and oxytocin (OXT) 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, while 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.
    Journal of Neuroendocrinology 01/2013; · 3.33 Impact Factor
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    ABSTRACT: Our biological clock, the suprachiasmatic nucleus (SCN), sets the pace of our life: it provides a rhythmic function to our sleep-wake cycle. In order to do so properly the SCN synchronizes our physiology to behavioral patterns by directing the autonomic and hormonal output of the hypothalamus to the different organs of the body that require a different setting - activity or inactivity - during particular phases of the day or night. In this chapter we show that this delicate balance requires that the SCN should not only provide an output to these organs but also be informed about the physiological state of the organs in order to adapt its output. This occurs via a hypothalamic neuronal network that provides the necessary input to the SCN. We argue that the feedback that the SCN receives from its hypothalamic target structures is essential to maintain a balance in our physiological functions, which fluctuate during the sleep-wake cycle. We propose that this crucial role of the hypothalamus in the homeostatic response is the reason why, e.g., in aging or depression, changes in the functioning of the biological clock, the SCN, lead to the development of pathology. In addition, if this balance is not adequately organized, for example, if the signals of the biological clock are violated by being active and eating during the night, as in shift work, one will be more susceptible to diseases such as hypertension, obesity, diabetes, and metabolic syndrome.
    Handbook of Clinical Neurology 01/2013; 117C:173-191.
  • Article: Preface.
    Ruud M Buijs, Dick F Swaab
    Handbook of Clinical Neurology 01/2013; 117C:ix-x.
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    ABSTRACT: To study whether sleep and circadian rhythm disturbances in patients with Huntington's disease (HD) arise from dysfunction of the body's master clock, the hypothalamic suprachiasmatic nucleus. Postmortem cohort study. Eight patients with HD and eight control subjects matched for sex, age, clock time and month of death, postmortem delay, and fixation time of paraffin-embedded hypothalamic tissue. Using postmortem paraffin-embedded tissue, we assessed the functional integrity of the suprachiasmatic nucleus in patients with HD and control subjects by determining the expression of two major regulatory neuropeptides, vasoactive intestinal polypeptide and arginine vasopressin. Additionally, we studied melatonin 1 and 2 receptor expression. Compared with control subjects, the suprachiasmatic nucleus contained 85% fewer neurons immunoreactive for vasoactive intestinal polypeptide and 33% fewer neurons for arginine vasopressin in patients with HD (P = 0.002 and P = 0.027). The total amount of vasoactive intestinal polypeptide and arginine vasopressin messenger RNA was unchanged. No change was observed in the number of melatonin 1 or 2 receptor immunoreactive neurons. These findings indicate posttranscriptional neuropeptide changes in the suprachiasmatic nucleus of patients with HD, and suggest that sleep and circadian rhythm disorders in these patients may at least partly arise from suprachiasmatic nucleus dysfunction. CITATION: van Wamelen DJ; Aziz NA; Anink JJ; van Steenhoven R; Angeloni D; Fraschini F; Jockers R; Roos RAC; Swaab DF. Suprachiasmatic nucleus neuropeptide expression in patients with Huntington's disease. SLEEP 2013;36(1):117-125.
    Sleep 01/2013; 36(1):117-25. · 5.10 Impact Factor
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    ABSTRACT: Multiple genetic and environmental factors play a role in the development and progression of Parkinson's disease (PD). The main neuropathological hallmark of PD is the degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta. To study genetic and molecular contributors to the disease process, there is a great need for readily accessible cells with prominent DAergic features that can be used for reproducible in vitro cellular screening. Here, we investigated the molecular phenotype of retinoic acid (RA) differentiated SH-SY5Y cells using genome wide transcriptional profiling combined with gene ontology, transcription factor and molecular pathway analysis. We demonstrated that RA induces a general neuronal differentiation program in SH-SY5Y cells and that these cells develop a predominantly mature DAergic-like neurotransmitter phenotype. This phenotype is characterized by increased dopamine levels together with a substantial suppression of other neurotransmitter phenotypes, such as those for noradrenaline, acetylcholine, glutamate, serotonin and histamine. In addition, we show that RA differentiated SH-SY5Y cells express the dopamine and noradrenalin neurotransmitter transporters that are responsible for uptake of MPP(+), a well known DAergic cell toxicant. MPP(+) treatment alters mitochondrial activity according to its proposed cytotoxic effect in DAergic neurons. Taken together, RA differentiated SH-SY5Y cells have a DAergic-like phenotype, and provide a good cellular screening tool to find novel genes or compounds that affect cytotoxic processes that are associated with PD.
    PLoS ONE 01/2013; 8(5):e63862. · 3.73 Impact Factor
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    ABSTRACT: Purpose: Parkinson's disease (PD) is a movement disorder mainly characterized by progressive neurodegeneration of dopaminergic (DAergic) neurons in the substantia nigra (SN). As yet, unknown molecular changes contribute to the development of PD leading to a great need for in vivo models that herald this disorder. Here we characterize an animal model presenting early PD pathology. Methods: Young, adult C57/BL6 mice were treated for five weeks twice a week with 15 mg/kg 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) in combination with 250 mg/kg probenecid. During the treatment mice were tested on their dopamine dependent movement skills. The integrity of their nigrostriatal system was examined through immunohistochemical studies. Results: During the treatment, mice developed dopamine-dependent movement deficits induced by loss of tyrosine hydroxylase (TH) positive nigrostriatal axon terminals. Immunohistochemical study identified astrogliosis and microgliosis in the SN but no decrease of TH immunostaining, demonstrating lack of DAergic neuron degeneration. We also observed formation of α-synuclein inclusion bodies in the SN. Conclusions: The combined features of this MPTP model appear to represent an early neurotoxic cellular stress to the SN neurons bearing a striking resemblance to the early stages of PD neuropathology. This model might prove very useful to investigate early neurodegenerative events in the nigrostriatal DAergic system and to study the effects of potential treatment strategies counteracting the early PD cellular changes.
    Restorative neurology and neuroscience 12/2012; · 2.93 Impact Factor
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    ABSTRACT: Suprasellar tumors with compression of the optic chiasm are associated with an impaired sleep-wake rhythm. We hypothesized that this reflects a disorder of the biological clock of the human brain, the suprachiasmatic nucleus (SCN), which is located just above the optic chiasm. In order to test this hypothesis, we investigated the expression of two key neuropeptides of the SCN, i.e. arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP), as assessed by quantitative immunocytochemistry in post-mortem hypothalamic tissue of patients with a suprasellar tumor inducing permanent visual field defects. Post-mortem hypothalamic tissue of five patients with a suprasellar tumor inducing permanent visual field defects (acromegaly n=2, nonfunctioning macro-adenoma n=1, macroprolactinoma n=1, infundibular metastasis of a colorectal adenocarcinoma n=1) and fifteen age- and gender-matched controls was obtained from the Netherlands Brain Bank. Total AVP-immunoreactivity in the SCN was lower in patients with a suprasellar tumor than in controls (p = 0.03). By contrast, total VIP-immunoreactivity was not different between patients and controls (p = 0.44). Suprasellar tumors leading to permanent visual field defects are associated with reduced AVP-, but not VIP-immunoreactivity in the SCN. These findings raise the possibility that selective impairment of the SCN contributes to sleep-wake disturbances in these patients.
    Brain Pathology 12/2012; · 4.74 Impact Factor

Publication Stats

4k Citations
843.97 Total Impact Points


  • 2006–2014
    • Netherlands Institute for Neuroscience
      Amsterdamo, North Holland, Netherlands
  • 2013
    • Universidad Nacional Autónoma de México
      • Department of Cellular Biology and Physiology
      Mexico City, The Federal District, Mexico
    • University of Leuven
      Louvain, Flanders, Belgium
  • 2004–2013
    • VU University Amsterdam
      • Department of Clinical Neuropsychology
      Amsterdamo, North Holland, Netherlands
  • 2002–2013
    • University of Science and Technology of China
      • • School of Life Sciences
      • • Department of Neurobiology and BioPhysics
      Hefei, Anhui Sheng, China
  • 2000–2013
    • University of Amsterdam
      • Faculty of Medicine AMC
      Amsterdamo, North Holland, Netherlands
  • 2012
    • Erasmus MC
      • Department of Internal Medicine
      Rotterdam, South Holland, Netherlands
  • 2002–2012
    • Koninklijke Nederlandse Akademie van Wetenschappen
      Amsterdamo, North Holland, Netherlands
  • 2010–2011
    • Zhejiang University
      • Department of Neurobiology
      Hang-hsien, Zhejiang Sheng, China
    • Chinese PLA General Hospital (301 Hospital)
      Peping, Beijing, China
    • Karolinska Institutet
      • Institutionen för klinisk neurovetenskap
      Solna, Stockholm, Sweden
  • 2002–2011
    • VU University Medical Center
      • Department of Psychiatry
      Amsterdam, North Holland, Netherlands
  • 2008
    • Kursk State Medical University
      Kursk, Kursk, Russia
  • 2001–2007
    • Russian Cardiology Research and Production Complex
      Moskva, Moscow, Russia
  • 1994–2007
    • Sociaal en Cultureel Planbureau
      's-Gravenhage, South Holland, Netherlands
  • 2002–2006
    • Athens State University
      Athens, Alabama, United States
  • 2005
    • Leiden University Medical Centre
      • Department of Neurology
      Leiden, South Holland, Netherlands
    • National and Kapodistrian University of Athens
      • Division of Psychiatry I of General Hospital
      Athens, Attiki, Greece
  • 2003
    • University of Surrey
      Guilford, England, United Kingdom
    • Leiden University
      Leyden, South Holland, Netherlands
    • Anhui Medical University
      Luchow, Anhui Sheng, China