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D F Swaab

Publications and source records attributed to D F Swaab.

At least 19 recordsLinked to original sources
PubMed2006

Beta-protein/A4 deposits are not associated with hyperphosphorylated tau in somatostatin neurons in the hypothalamus of Alzheimer's disease patients.

With respect to the pathogenesis of Alzheimer's disease (AD), it has been hypothesized that amorphous plaques containing beta-protein/A4 (Abeta) would locally induce cytoskeletal changes, and that neurons affected by neurofibrillary tangles (NFTs) lose their neuropeptide concentration and eventually die. To test this presumed cascade of events, the hypothalami of 14 non-demented subjects (Braak 0-III) and 28 AD patients (Braak IV-VI) aged 40-98 years were selected. The subject of our study was the nucleus tuberalis lateralis (NTL), which harbors a subpopulation of somatostatinergic neurons with extensive intrinsic interconnectivity. We used Gallyas silver staining, Congo staining, single- and double-staining with monoclonal antibody AT8 and polyclonal antibody anti-Abeta, and double-immunolabeling with AT8 and anti-somatostatin(1-12) with the following results: (1) Significant amounts of silver-staining NFTs were present in only three AD patients. (2) High densities of AT8-stained cytoskeletal changes were mainly found in aged, demented patients. (3) In contrast, large amounts of Abeta deposits were mainly observed in young and middle-aged (40-59 years) AD patients, and were very low or absent mainly in the older non-demented subjects and in AD patients. (4) Reduced anti-somatostatin staining was observed in the NTL of most AD patients, but anti-somatostatin/AT8 double-stained neurons were found virtually exclusively in aged AD patients. Thus, the occurrence of Abeta deposits and hyperphosphorylated tau formation in somatostatin cells are basically independent events, while decreased somatostatin staining only partly goes together with cytoskeletal changes in somatostatin cells in the NTL of AD patients. These observations cannot be explained by the amyloid cascade hypothesis.

Adult↗
PubMed2006

A direct androgenic involvement in the expression of human corticotropin-releasing hormone.

We investigated the possibility of a direct action of androgens on the expression of the human corticotropin-releasing hormone (CRH), which plays a central role in the hypothalamic-pituitary-adrenal (HPA)-axis. Colocalization of CRH and nuclear/cytoplasmic androgen receptor (AR) was found in neurons of the paraventricular nucleus (PVN) in the human hypothalamus. A potential androgen-responsive element (ARE) in the human CRH promoter was subsequently analyzed with bandshifts and cotransfections in neuroblastoma cells. In the presence of testosterone, recombinant human AR bound specifically to the CRH-ARE. Expression of AR in combination with testosterone repressed CRH promoter activity through the ARE. We conclude that androgens may directly affect CRH neurons in the human PVN via AR binding to the CRH-ARE, which may have consequences for sex-specific pathogenesis of mood disorders.

Adult↗
PubMed2005

Physical activity and executive functions in the elderly with mild cognitive impairment.

The primary goal of the present study was to examine whether in the elderly with mild cognitive impairment (MCI), the effect of physical activity measured directly following treatment, was reflected in an improvement in cognitive functioning in general or in executive functions (EF) in particular. Secondly, this study aimed to compare the effectiveness of two types of intervention, with varying intensities: walking and hand/face exercises. Forty-three frail, advanced elderly subjects (mean age: 86) with MCI were randomly divided into three groups, namely, a walking group (n=15), a group performing hand and face exercises (n=13), and a control group (n=15). All subjects received individual treatment for 30 minutes a day, three times a week, for a period of six weeks. A neuropsychological test battery, administered directly after cessation of treatment, assessed cognitive functioning. The results show that although a (nearly) significant improvement in tasks appealing to EF was observed in both the walking group and the hand/face group compared to the control group, the results should be interpreted with caution. Firm conclusions about the effectiveness of mild physical activity on EF in the oldest old can only be drawn after studies with larger number of subjects.

Activities of Daily Living↗
PubMed2005

[Chronic pain in dementia and in disorders with a high risk for congnitive impairment].

Ageing increases the risk for the etiology of chronic pain and dementia. hence, the increase in the number of elderly people implies that the number of elderly with dementia suffering from chronic pain will increase as well. A key question relates to if and how patients with dementia perceive pain. the inadequateness of pain assessment, particularly in a more advanced stage, is also reflected in a decreased use of analgesics by elderly people with dementia. Insight into possible changes in pain experience as have been observed in the few available clinical studies, could be enhanced by knowledge about the neuropathology which may differ per subtype of dementia. It is striking that pain has not been examined in degenerative diseases of the central nervous system with a high risk for cognitive impairment such as Parkinson's disease and multiple sclerosis. In these disorders, pain is a prominent clinical symptom and to date it is not known whether the experience of pain will change in a stage in which patients become cognitively impaired. Finally, a number of instruments which are most appropriate to assess pain in communicative and non-communicative patients are discussed.

Aging↗
PubMed2004

Glucocorticoids decrease thyrotropin-releasing hormone messenger ribonucleic acid expression in the paraventricular nucleus of the human hypothalamus.

The way glucocorticoids affect TRH mRNA expression in the paraventricular nucleus of the hypothalamus is still unclear. In view of its relevance for Cushing's syndrome and depression, we measured TRH mRNA expression in human hypothalami obtained at autopsy by means of quantitative TRH mRNA in situ hybridization. In corticosteroid-treated subjects (n = 10), TRH mRNA hybridization signal was decreased as compared with matched control subjects (n = 10) (Mann-Whitney U test, P = 0.02). By inference, hypercortisolism as present in patients with Cushing's syndrome or major depression may contribute to lower serum TSH or symptoms of depression by lowering hypothalamic TRH expression.

Adult↗
PubMed2004

Alzheimer's disease and NGF signaling.

Age-related degeneration of basal forebrain cholinergic neurons (BFCNs) occurs early and contributes significantly to cognitive decline in Alzheimer's disease (AD). Proper function and morphology of BFCNs depends on the supply of nerve growth factor (NGF) from the cortex and the hippocampus. A large number of experiments have shown that decreased supply of NGF at the level of BFCN cell bodies leads to loss of neuronal markers and shrinkage, mimicking what is observed in AD. The delivery of sufficient amounts of NGF signal to BFCN cell bodies depends on the effective participation of several factors including sufficient synthesis and release of NGF, adequate synthesis and expression of NGF receptors by BFCNs, normal signaling and retrograde transport of NGF-receptor complex, and finally effective induction of gene expression by NGF. In the past few years it has become clear that decreased amounts of NGF at the level of BFCN cell bodies is largely due to failed retrograde transport rather than decreased synthesis, binding or expression of NGF receptors in the BFCN terminals. We will discuss in vivo evidence supporting decreased retrograde transport of NGF in a mouse model with BFCN degeneration, and will attempt to match these findings with our studies in postmortem human AD brain. We will speculate about the possible mechanisms of failed NGF retrograde transport and its relationship to AD pathology.

Alzheimer Disease↗
PubMed2004

Sexual differentiation of the human brain: relevance for gender identity, transsexualism and sexual orientation.

Male sexual differentiation of the brain and behavior are thought, on the basis of experiments in rodents, to be caused by androgens, following conversion to estrogens. However, observations in human subjects with genetic and other disorders show that direct effects of testosterone on the developing fetal brain are of major importance for the development of male gender identity and male heterosexual orientation. Solid evidence for the importance of postnatal social factors is lacking. In the human brain, structural diferences have been described that seem to be related to gender identity and sexual orientation.

Animals↗
PubMed2004

Long-term effects of cranial irradiation for childhood malignancy on sleep in adulthood.

BACKGROUND: Cranial radiation therapy (CRT) is required for successful treatment of a variety of brain tumours in childhood. OBJECTIVE: To investigate whether childhood CRT leads to altered sleep-wakefulness organization in adulthood, and to identify the determinants of such alterations. SUBJECTS AND METHODS: Subjective (questionnaires) and objective (actigraphy) measures of circadian rhythmicity and sleep were assessed in 25 individuals, 8-29 years after CRT for medulloblastoma (n=17) or other intracranial tumours (n=8), and in a group of 34 age-matched healthy individuals. Serum GH peak during insulin-induced hypoglycaemia and serum concentrations of prolactin and leptin (expressed per fat mass) were determined in the CRT group. RESULTS: The CRT group showed a markedly increased sleep duration (8.66 h, compared with 7.66 h in controls). In addition, the sleep-wake rhythm showed greater amplitude and less fragmentation, and less tolerance for alterations in the timing of sleep. Regression analysis showed both radiation dosage and neuroendocrine status to be determinants of sleep changes, suggesting that some of the alterations may be normalized with hormone supplementation. CONCLUSION: The present study shows that high-dose cranial radiation therapy in childhood is associated with objective and subjective changes in the sleep-wake rhythm in adulthood.

Adolescent↗
PubMed2003

Early social stress in male Guinea-pigs changes social behaviour, and autonomic and neuroendocrine functions.

The present study was undertaken to investigate the effects of pre- and early postnatal social stress on the functioning of hormonal, autonomic and behavioural systems, by studying the distribution of sex hormone receptors in limbic brain systems. Dams had either lived in groups with a constant composition (= stable social environment) or in groups with changing compositions, i.e. every third day, two females from different groups were exchanged (= unstable social environment). The subjects were male offspring of dams who had either lived in a stable social environment during pregnancy and lactation (= control males) or in an unstable social environment during this period of life (= early stressed males). From days 20-80, the spontaneous behaviour of control males and early stressed males was recorded in their home cages. Five control males and five early stressed males were killed at 75 days, and five control males and five early stressed males at 120 days. Blood samples were taken to determine serum concentrations of cortisol, testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulphate and oestrogen. The adrenals were prepared to determine tyrosine hydroxylase activities and the brains were used to investigate the distribution of sex-hormone receptors in specific hypothalamic and hippocampal brain areas. Early stressed males showed a behavioural infantilization that was accompanied by significantly decreased adrenal tyrosine hydroxylase activities and dehydroepiandrosterone levels. Furthermore, early stressed males showed a down-regulation of androgen receptors in the medial preoptic area and the nucleus arcuatus of the hypothalamus, as well as of oestrogen receptor alpha in the hippocampus compared to control males. Thus, the present study provides clear evidence that early social stress induces changes in endocrine, autonomic and limbic brain function, which is mirrored by changes in male social behaviour.

Animals↗
PubMed2002

Co-localization of histamine with GABA but not with galanin in the human tuberomamillary nucleus.

The presence of GABA and galanin in histaminergic neurons was previously reported in the rodent brain but whether such co-localizations also occur in the human brain was not known. We used in situ hybridization histochemistry and immunohistochemistry to study the co-localization of histamine with GABA and galanin in neurons of the tuberomamillary nucleus of adult human posterior hypothalamus. On consecutive formalin-fixed paraffin-embedded sections, co-localization was assessed using the in situ hybridization for L-histidine decarboxylase mRNA and immunocytochemistry for glutamate decarboxylase-67 kDa or galanin in the two profiles of same cell. The pattern of distribution and number of histaminergic neurons identified by in situ hybridization of the synthesizing enzyme gene transcripts were in accordance with data reported for histamine immunoreactivity. The great majority of neurons within the main divisions of the tuberomamillary nucleus containing L-histidine decarboxylase mRNA was also immunoreactive for glutamate decarboxylase-67 kDa. The range of co-localization of the two markers varied from 72% in the lateral part, to 75-87% in the medial part and 83-88% in the ventral part. In contrast, no cell containing L-histidine decarboxylase mRNA was immunoreactive for galanin. We conclude that tuberomamillary neurons in human co-express histamine with GABA but, unlike the neurons in rodents, do not express galanin, indicating that neurotransmitter co-localization patterns differ in the two species.

Adult↗
PubMed2002

Cranial electrostimulation (CES) in patients with probable Alzheimer's disease.

In one study, behavioral disorders of patients with vascular dementia reacted positively to cranial electrostimulation (CES). In the present study, it was examined whether CES could improve cognition and (affective) behavior in patients with probable Alzheimer's disease (AD). Eighteen AD patients, divided into an experimental and a placebo group, were treated for 30 min per day, 5 days a week, for 6 weeks. No improvements in cognition and (affective) behavior were found after CES.

Aged↗
PubMed2002

Brain aging and Alzheimer's disease; use it or lose it.

(1) Alzheimer's disease is a multifactorial disease in which age and APOE-epsilon 4 are important risk factors. (2) The neuropathological hallmarks of AD, i.e. amorphous plaques, neuritic plaques (NPs), pretangles, neurofibrillary tangles (NFT) and cell death are not part of a single pathogenetic cascade but may occur independently. (3) In brain areas where classical AD changes, i.e. NPs and NFTs, are present, such as the CA1 area of the hippocampus, the nucleus basalis of Meynert and the tuberomamillary nucleus, a decreased metabolic rate is found. The decreased metabolic rate appears not to be induced by the presence of pretangles, NFT or NPs. (4) Decreased metabolic rate may precede cognitive impairment and is thus an early occurring hallmark of AD, which, in principle, may be reversible. The observation that the administration of glucose or insulin enhances memory in AD patients also supports the view that AD has a metabolic basis. (5) Moreover, several observations in postmortem brain indicate that activated neurons are better able to withstand aging and AD, a phenomenon paraphrased by us as 'use it or lose it'. (6) It is, therefore, attractive to direct the development of therapeutic strategies towards restimulation of neuronal metabolic rate in order to improve cognition and other symptoms in AD. A number of pharmacological and non-pharmacological studies support the concept that activation of the brain has beneficial effects and may, to a certain degree, restore several aspects of cognition and other central functions. For instance, the circadian system may be restimulated in AD patients by exposing them to more light or transcutaneous nerve stimulation. A procedure has been developed to culture human postmortem brain tissue that allows testing of the efficacy of putative stimulatory compounds such as neurotrophins.

Aging↗
PubMed2002

Senescence, sleep, and circadian rhythms.

The goal of this review article is to summarize our knowledge and understanding of the overlapping (interdisciplinary) areas of senescence, sleep, and circadian rhythms. Our overview comprehensively (and visually wherever possible), emphasizes the organizational, dynamic, and plastic nature of both sleep and circadian timing system (CTS) during senescent processes in animals and in humans. In this review, we focus on the studies that deal with sleep and circadian rhythms in aged animals and how these studies have closely correlated to and advanced our understanding of similar processes in ageing humans. Our comprehensive summary of various aspects of the existing research on animal and human ageing, both normal and pathological, presented in this review underscores the invaluable advantage of close collaboration between clinicians and basic research scientists and the future challenges inherent in this collaboration. First, our review addresses the common age-related changes that occur in sleep and temporal organization of both animals and humans. Second, we examine the specific modifications that often accompany sleep and CTS during aging. Third, we discuss the clinical epidemiology of sleep dysfunctions during ageing and their current clinical management, both pharmacological and non-pharmacological. Finally, we predict the possible future promises for complementary and alternative medicine (CAM) that pave the way to the emergence of a "Holistic Sleep Medicine" approach to the treatment of sleep disorders in the ageing population. Further studies will provide additional valuable insights into the understanding of both sleep and circadian rhythms during senescence.

Aging↗
PubMed2002

Cortisol is increased in postmortem cerebrospinal fluid of multiple sclerosis patients: relationship with cytokines and sepsis.

Hypothalmo-pituitary-adrenal (HPA) axis activity is altered in patients with multiple sclerosis (MS), resulting in elevated basal levels and enhanced response of cortisol in stimulation tests. HPA axis hyperactivation in MS is thought to be the result of complex interactions of genetic, immunologic, and neuroendocrinological mechanisms. In order to investigate whether cytokine levels in the central nervous system are associated with the activation of the HPA axis in MS, we measured cortisol, interleukin (IL)-6, IL-10 and TNF-alpha levels in postmortem cerebrospinal fluid (CSF) of 18 patients with severe MS and 50 controls. We also investigated the cortisol and cytokine levels in the CSF of a group of MS patients and controls who died with sepsis, in order to see whether acute infectious situations affect the association between cortisol and cytokines. The cortisol levels in MS patients were increased by 80% in comparison to controls (p=0.008). There was no difference in IL-6 levels between the groups, while IL-10 and TNF-alpha levels of the majority of subjects were below detection limits. There was a positive correlation between cortisol and IL-6 only in control patients with sepsis (r=0.89, p=0.019), but not within the MS patents with sepsis or MS and control groups without sepsis. Cortisol levels in postmortem serum and CSF were highly correlated (r>0.78, p<0.001). We concluded that the basal level of cortisol is significantly increased in the CSF of MS patients and that IL-6 is not responsible for this rise. The relationship between cortisol and IL-6 in sepsis is discussed.

Aged↗
PubMed2002

Glucocorticoid treatment is associated with decreased expression of processed AVP but not of proAVP, neurophysin or oxytocin in the human hypothalamus: are PC1 and PC2 involved?

OBJECTIVES: We reported earlier that vasopressin (AVP) peptide expression is significantly decreased in the postmortem hypothalamus of glucocorticoid (GC) treated patients, while such a decrease was not observed in AVP prohormone (proAVP) expression. This indicated a GC-induced suppression of AVP synthesis at the posttranslational level. Here, we investigated in detail whether this decreased levels of AVP expression in GC treated patients might be due to the down regulation of the prohormone convertases PC-1 and PC-2, and the molecular chaperone 7B2, as was reported previously in some AVP-related disorders. MATERIALS & METHODS: An immunocytochemical study was performed on post-mortem hypothalami of GC exposed patients and controls, in which quantification of proAVP, AVP, neurophysin (NP) and oxytocin (OXT) expression were done along with the quantification of PC1, PC2 and 7B2 expression in the paraventricular nucleus, by using a computerized image analysis system. RESULTS: Expression of processed AVP in GC exposed patients was significantly decreased (p=0.021), while the amount of proAVP expression was unchanged. Despite the strong correlation between AVP and NP (the other cleavage product of proAVP) expression in the GC group (r=0.917, p=0.004), the mean NP immunoreactivity did not show a significant decrease in this group. Also the OXT expression was similar in both groups. Although in most of the GC treated patients, the expression intensities of PC1 and PC2 were decreased parallel to the decrease in AVP, the mean expression levels of neither of PC1 and PC2, nor of 7B2 were statistically different between the groups (p=0.20-0.80). CONCLUSION: We conclude that the suppression of AVP expression by GCs is not mediated solely by the down regulation of PC1, PC2 or 7B2. Other mechanisms, which may contribute to the GC-induced posttranslational suppression of AVP, are discussed.

Adult↗