A5031662512- Stress Responses and Cortisol
- Neuroscience and Neuropharmacology Research
- Ion Channels and Receptors
- Diet and metabolism studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Metabolism and Genetic Disorders
- Neuroendocrine regulation and behavior
- Tryptophan and brain disorders
- Alzheimer's disease research and treatments
- Liver Disease Diagnosis and Treatment
- Mitochondrial Function and Pathology
- Growth Hormone and Insulin-like Growth Factors
- Neurogenesis and neuroplasticity mechanisms
- Ion channel regulation and function
- Postharvest Quality and Shelf Life Management
- Circadian rhythm and melatonin
- Adrenal Hormones and Disorders
- Microbial Inactivation Methods
- Phytochemicals and Antioxidant Activities
- Neurological Disease Mechanisms and Treatments
- Herbal Medicine Research Studies
- Medicinal Plants and Neuroprotection
- Inflammasome and immune disorders
- Diabetes Treatment and Management
- S100 Proteins and Annexins
Danone Nutricia Research (Netherlands)
2018-2024
Nutricia Research (Netherlands)
2016-2024
Danone (Netherlands)
2018-2024
Novartis (United Kingdom)
2012-2015
Horsham Hospital
2012
Friedrich Miescher Institute
2006
University of Amsterdam
1978-2005
Netherlands Institute for Neuroscience
2003-2004
Englerin A is a structurally unique natural product reported to selectively inhibit growth of renal cell carcinoma lines. large scale phenotypic profiling experiment (CLiP) englerin on ¬over 500 well characterized cancer lines showed that inhibits subset tumor from many lineages, not just carcinomas. Expression the TRPC4 cation channel was line feature best correlated with sensitivity A, suggesting hypothesis efficacy target for A. Genetic experiments demonstrate expression both necessary...
Abstract Chronic stress causes disinhibition of the hypothalamus–pituitary–adrenal axis. Consequently, brain is overexposed to glucocorticoids which in humans may precipitate stress‐related disorders, e.g. depression. The activity strongly regulated by GABAergic input parvocellular neurons hypothalamic paraventricular nucleus. We here report a reduced frequency miniature inhibitory postsynaptic currents (mIPSCs) rats exposed 3 weeks unpredictable stress. mIPSC amplitude and kinetic...
Abstract Parvocellular neurons in the hypothalamic paraventricular nucleus receive hormonal inputs mediated by corticosterone as well neuronal inputs, prominent among which is a GABAergic inhibitory projection. In present study we examined functional properties of this innervation when corticosteroid levels fluctuate. Frequency, amplitude and kinetic miniature postsynaptic potentials (mIPSCs), γ amino butyric acid (GABA) were studied with whole cell recording parvocellular neurons. Injection...
Abstract Activation of hippocampal glucocorticoid receptors in vitro increases calcium current amplitude through a process requiring DNA binding receptor homodimers. We here investigated (i) whether similar increased currents also occur following vivo activation due to stress and (ii) if so, this can be explained by expression channel subunits. Rats were exposed novelty stress; some the animals pretreated with antagonist. In subsequently prepared slices, recorded from identified CA1...
A high throughput screening campaign identified 5-(2-chlorophenyl)indazole compound 4 as an antagonist of the transient receptor potential A1 (TRPA1) ion channel with IC50 = 1.23 μM. Hit to lead medicinal chemistry optimization established SAR around indazole ring system, demonstrating that a trifluoromethyl group at 2-position phenyl in combination various substituents 6-position greatly contributed improvements vitro activity. Further resulted identification 31, potent and selective TRPA1...
Rationale: Traumatic brain injury (TBI) leads to neurological impairment, with no satisfactory treatments available.Classical ketogenic diets (KD), which reduce reliance on carbohydrates and provide ketones as fuel, have neuroprotective potential, but their high fat content reduces compliance, experimental evidence suggests they protect juvenile against TBI, not adult brain, would strongly limit applicability in TBI.Methods: We designed a new-KD carbohydrate plus protein ratio of 2:1,...
Abstract The classic ketogenic diet is an effective treatment option for drug-resistant epilepsy, but its high fat content challenges patient compliance. Optimizing liver ketone production guided by a method comparing substrates their potential may help to reduce the of without loss in ketosis induction. Here, we present cell assay measuring β-hydroxybutyrate (βHB) yield from fatty acid substrates. Even chain albumin-conjugated acids comprising between 4 and 18 carbon atoms showed sigmoidal...
Within the rat paraventricular nucleus of hypothalamus two types neurons have been distinguished based on morphological appearance, i.e., parvocellular and magnocellular neurons. The play a key role in regulating activity hypothalamo-pituitary-adrenal axis, which is activated, e.g., after stress exposure. These receive humoral negative feedback via adrenal hormone corticosterone but also neuronal inhibitory input, either directly or transsynaptically relayed GABAergic interneurons. In...
The transient receptor potential channel subtype A member 1 (TRPA1) is a nonselective cation widely viewed as having therapeutic potential, particularly for pain-related indications. Realization of this will require potent, selective modulators; however, currently the pharmacology TRPA1 poorly defined. As calcium permeable, indicators offer simple assay format high-throughput screening. In report, we show that probenecid, uricosuric agent used experimentally in screening to increase loading...
Neuronal and synaptic membranes are composed of a phospholipid bilayer. Supplementation with dietary precursors for synthesis –docosahexaenoic acid (DHA), uridine choline– has been shown to increase neurite outgrowth synaptogenesis both in vivo vitro. A role multi-nutrient intervention specific cofactors recently emerged early Alzheimer's disease, which is characterized by decreased synapse numbers the hippocampus. Moreover, medical food Souvenaid, containing nutrient combination Fortasyn...
Astrocytes are specialized glial cells that tile the central nervous system (CNS) and perform numerous essential functions. react to various forms of CNS insults by altering their morphology molecular profile, through a process known as reactive astrogliosis. Accordingly, astrocyte reactivity is apparent in many neurodegenerative diseases, among which one Alzheimer's disease (AD). Recent clinical trials on early-stage AD have demonstrated Fortasyn Connect (FC), multi-nutrient combination...
Phenylketonuria (PKU) is an inborn error of metabolism. Mutations in the enzyme phenylalanine hydroxylase (PAH)-encoding gene lead to a decreased metabolism amino acid (Phe). The deficiency PAH increases Phe levels blood and brain. Accumulation can delayed development, psychiatric problems cognitive impairment. White matter (WM) damage neuropathological hallmark PKU be seen even early detected treated patients. mechanisms linking high concentrations WM abnormalities remain unclear. We tested...
GPR39 is a GPCR implicated as regulator of gastrointestinal motility, although the mechanism remains elusive. Here, we report that expressed by specific cell population cultured from mouse small intestine muscle layers, which was subsequently identified fibroblast-like cells (FLCs) have recently been shown to modulate gut motility. Application agonist, Zn(2+), induced large currents and membrane depolarization in FLCs wild-type mice, but not Gpr39(-/-) mice. This Zn(2+)-induced current could...
Summary Introduction A possible target for stroke management is modulation of neuroinflammation. Evidence suggests that food components may exert anti‐inflammatory properties and thus reduce stroke‐induced brain damage. Aim To investigate the efficacy a diet, containing ingredients, as treatment focal ischemic damage induced by photothrombotic in somatosensory cortex rats. Results Brain lesions were surrounded strong astrogliosis on both day 7 21 after accompanied trend toward globally...
The canonical transient receptor potential channel subfamily (TRPC3, TRPC6, and TRPC7) contains Ca(2+) permeable non-selective cation channels that are widely expressed in a variety of tissues. There is increasing evidence implicating TRPC channels, particularly TRPC3 6, physiological pathophysiological processes, eliciting interest these as novel drug targets. Electrophysiology remains benchmark technique for measuring ion function accurately determining the pharmacological effects...
The case history of a patient with Budd-Chiari syndrome (BCS) is described. underlaying disease proved to be essential thrombocytosis. Congential elliptocytosis was also present. value the conventional liver scan, percutaneous splenoportoscintigraphy and isotopic phlebography inferior vena cava in diagnosis BCS It suggested that combination these three noninvasive techniques used when suspected.