ORCID Profile
0000-0002-5018-8924
Current Organisation
Northumbria University
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Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.SCHRES.2018.11.011
Abstract: Recent transcriptomic, proteomic and metabolomics studies have highlighted an abnormal cerebral glucose and energy metabolism as one of the potential pathophysiological mechanisms of schizophrenia. This raises the possibility that a metabolically-based intervention might have therapeutic value in the management of schizophrenia, a notion supported by our recent results that a low carbohydrate/high-fat therapeutic ketogenic diet (KD) prevented a variety of behavioural abnormalities induced by pharmacological inhibition of NMDA glutamate receptors. Here we asked if the beneficial effects of KD can be generalised to impaired prepulse inhibition of startle (PPI), a translationally validated endophenotype of schizophrenia, in a pharmacological model in mice. Furthermore, we addressed the issue of whether the effect of KD is linked to the calorie-restricted state typical of the initial phase of KD. We fed male C57BL/6 mice a KD for 7 weeks and tested PPI at 3 and 7 weeks, in the presence and absence of a significant digestible energy deficit, respectively. We used an NMDA receptor hypo-function model of schizophrenia induced by acute injection of dizocilpine (MK-801). We found that KD effectively prevented MK-801-induced PPI impairments at both 3 and 7 weeks, irrespective of the presence or absence of digestible energy deficit. Furthermore, there was a lack of correlation between PPI and body weight changes. These results support the efficacy of the therapeutic KD in a translational model of schizophrenia and furthermore provide evidence against the role of calorie restriction in its mechanism of action.
Publisher: Springer Science and Business Media LLC
Date: 31-01-2017
DOI: 10.1038/SREP41760
Abstract: First Nations people globally have a higher incidence of mental disorders and non-communicable diseases. These health inequalities are partially attributed to a complex network of social and environmental factors which likely converge on chronic psychosocial stress. We hypothesized that alterations in stress processing and the regulation of the hypothalamic-pituitary-adrenal axis might underlie health disparities in First Nations people. We assessed the cortisol awakening response and the dynamic response to a laboratory induced psychosocial stress of young Indigenous tertiary students (n = 11, mean age 23.82 years) and non-Indigenous students (n = 11) matched for age and gender. Indigenous participants had a blunted cortisol awakening response (27.40 (SD 35.00) vs. 95.24 (SD 55.23), p = 0.002), which was differentially associated with chronic experience of stress in Indigenous (r = −0.641, p = 0.046) and non-Indigenous (r = 0.652, p = 0.03) participants. The cortisol response to the laboratory induced psychosocial stress did not differ between groups. Self-reported racial discrimination was strongly associated with flattened cortisol response to stress (r = −0676, p = 0.022) and with heart rate variability (r = 0.654, p = 0.040). Our findings provide insight into potential biological factors underlying health discrepancies in ethnic minority groups.
Publisher: Springer New York
Date: 11-12-2019
DOI: 10.1007/978-1-4939-8994-2_5
Abstract: The forced swim test assesses learned helplessness, which is a feature of depression-like behavior in rodents. This test has also been used in testing the efficacy of existing and novel antidepressant drugs. It is based on the natural tendency of rodents to escape from water. Rodents are placed in a cylinder filled with water and the presumption is that those with a depression-like phenotype give up swimming earlier than those that are not depressed. Furthermore, antidepressant drugs reverse this effect. This chapter describes the basic setup and conduction of the test, along with interpretation of the results. It should be emphasized that this test should be conducted as part of a series of behavioral assessments in order to increase the accuracy of the results.
Publisher: Springer New York
Date: 11-12-2019
DOI: 10.1007/978-1-4939-8994-2_6
Abstract: Obsessive-compulsive disorder (OCD) can occur in several psychiatric illnesses such as autism spectrum disorders (ASD) and it is more prevalent in children. This condition is characterized by repeated and apparently meaningless behaviors such as frequent hand washing, counting, tapping, and rocking. This can disrupt normal socialization and in some cases lead to self-harm. Therefore there is interest in developing more effective therapies for in iduals suffering from these conditions. This chapter describes how to conduct the mouse marble burying test as a sensitive measure of compulsive behaviors.
Publisher: Oxford University Press (OUP)
Date: 27-05-2016
Publisher: Springer New York
Date: 11-12-2019
DOI: 10.1007/978-1-4939-8994-2_7
Abstract: This chapter presents a method for assessing general behavior, well-being, and sensorimotor gating. A detailed protocol is given for assessment of nest building performance in female mice using a strict scoring system. The test can be used for assessing moods and behaviors associated with psychiatric disorders such as depression and schizophrenia. It can also be useful for testing movement disorders such as Parkinson disease.
Publisher: Springer New York
Date: 11-12-2019
DOI: 10.1007/978-1-4939-8994-2_10
Abstract: The Y-maze can be used to assess short term memory in mice. Spontaneous alternation, a measure of spatial working memory, can be assessed by allowing mice to explore all three arms of the maze and is driven by an innate curiosity of rodents to explore previously unvisited areas. A mouse with intact working memory, and hence intact prefrontal cortical functions, will remember the arms previously visited and show a tendency to enter a less recently visited arm. Spatial reference memory, which is underlined by the hippoc us, can also be tested by placing the test mice into the Y-maze with one arm closed off during training. After an inter-trial interval of for ex le 1 h, the mouse should remember which arm it has not explored previously and should visit this arm more often. This chapter describes the pre-test conditions, the materials required and the protocol for conducting and interpreting the results of these two related tests.
Publisher: Springer New York
Date: 11-12-2019
DOI: 10.1007/978-1-4939-8994-2_8
Abstract: Psychiatric disorders affect approximately one quarter of people worldwide at some point in their lifetime. This chapter provides a step-by-step guide to conduct behavioral tests in adult mice for investigations of social behavior, without the need for specific equipment. This test should allow the identification of key abnormalities in social interactions that can be followed up by targeted, more complex, behavioral analysis aimed at identification of new biomarkers and potential drug targets.
Publisher: Springer New York
Date: 11-12-2019
DOI: 10.1007/978-1-4939-8994-2_9
Abstract: The open field test is used in studies of the neurobiological basis of anxiety and screening for novel drug targets and anxiolytic compounds. This test uses a camera to measure movement of the test animal in the peripheral and central zones of a 42 × 42 × 42 cm polyvinyl chloride box. This chapter describes a protocol for carrying out the open-field test for assessment of locomotion and anxiety-like behavior in mice.
Publisher: Springer International Publishing
Date: 2019
DOI: 10.1007/978-3-030-25650-0_5
Abstract: This chapter reviews the efficacy of the ketogenic diet in a variety of neurodegenerative, neurodevelopmental and metabolic conditions throughout different stages of life. It describes conditions affecting children, metabolic disorders in adults and disorderrs affecting the elderly. We have focused on application of the ketogenic diet in clinical studies and in preclinical models and discuss the benefits and negative aspects of the diet. Finally, we highlight the need for further research in this area with a view of discovering novel mechanistic targets of the ketogenic diet, as a means of maximising the potential benefits/risks ratio.
Publisher: Frontiers Media SA
Date: 11-08-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2019
Publisher: Springer Science and Business Media LLC
Date: 04-11-2022
DOI: 10.1186/S12872-022-02918-W
Abstract: A previous study found that circulating angiopoietin-1 (angpt-1) concentrations were significantly lower in patients who had a recent ischaemic stroke compared to healthy controls. The primary aim of this study was to assess whether serum angpt-1 could be used as a diagnostic test of ischemic stroke in patients presenting to hospital as an emergency. Exploratory analyses investigated the association of proteins functionally related to angpt-1 (angpt-2, Tie-2, matrix metalloproteinase-9 and vascular endothelial growth factors A, C and D) with ischaemic stroke diagnosis. Patients presenting to Townsville University Hospital for emergency assessment of stroke-like symptoms were consecutively recruited and provided a blood s le. After assessment by a consultant neurologist, patients were grouped into those who did, or did not have ischaemic stroke. The potential for serum angpt-1 to diagnose ischaemic stroke was assessed using receiver operator characteristic (ROC) curves. Cross-sectional analyses appraised inter-group differences in the serum concentration of other proteins. One-hundred and twenty-six patients presenting to Townsville University Hospital for emergency assessment of stroke-like symptoms were recruited (median time from symptom onset to hospital presentation: 2.6 (inter-quartile range: 1.2–4.6) hours). Serum angpt-1 had poor ability to diagnose ischaemic stroke in analyses using the whole cohort, or in sensitivity analyses (area under the ROC curve 0.51 (95% CI: 0.41–0.62) and 0.52 (95% CI: 0.39–0.64), respectively). No associations of serum angpt-1 concentration with ischaemic stroke severity, symptom duration or aetiology were observed. Serum concentrations of the other assessed proteins did not differ between patient groups. Serum angpt-1 concentration is unlikely to be useful for emergency diagnosis of ischaemic stroke.
Publisher: Elsevier BV
Date: 12-2015
Publisher: Springer US
Date: 2020
Publisher: Springer New York
Date: 2018
DOI: 10.1007/978-1-4939-7614-0_28
Abstract: Early parental nutritional interventions during prenatal development have been shown to result in neuropsychiatric sequelae in the adult offspring. In order to understand the impact of such nutritional interventions, the behavior of the animal has to be carefully analyzed. This chapter provides a step-by-step guide to conduct behavioral tests in adult mice for investigators without specific expertise or those without the equipment to carry out behavioral studies. We focus on tests tapping into the main behavioral abnormalities that correspond to mental illnesses. We describe the materials required and the detailed methods to conduct global assessment of parameters such as behavioral integrity and general well-being, psychomotor activity, social behavior, repetitive behavior, anxiety-like behavior, depression-like behavior, short-term spatial working memory, and spatial reference memory.
Publisher: Elsevier BV
Date: 10-2016
Publisher: Springer New York
Date: 11-12-2019
DOI: 10.1007/978-1-4939-8994-2_4
Abstract: The elevated plus maze test is used to measure anxiety-like behavior in rodents. It can be used to gain insight into conditions such as posttraumatic stress disorder (PTSD) and other conditions marked by anxious behavior. It can also be used as a component in screening of novel compounds for anxiolytic properties. This model is based on aversion to open spaces, which is seen as the animal spending more time in the enclosed arms of the maze. This chapter describes the steps necessary for setting up and conducting the test, along with interpretation of the results.
Publisher: Springer Science and Business Media LLC
Date: 28-01-2020
DOI: 10.1007/S00213-020-05467-2
Abstract: Impaired cerebral glucose metabolism is a core pathological feature of schizophrenia. We recently demonstrated that a ketogenic diet, causing a shift from glycolysis to ketosis, normalized schizophrenia-like behaviours in an acute N-methyl-D-aspartate (NMDA) receptor antagonist model of the illness. Ketogenic diet produces the ketone body, β-hydroxybutyrate (BHB), which may serve as an alternative fuel source in its own right without a strict dietary regime. We hypothesized that chronic administration of BHB replicates the therapeutic effects of ketogenic diet in an acute NMDA receptor hypofunction model of schizophrenia in mice. C57Bl/6 mice were either treated with acute doses of 2 mmol/kg, 10 mmol/kg, or 20 mmol/kg BHB or received daily intraperitoneal injections of 2 mmol/kg BHB or saline for 3 weeks. Behavioural testing assessed the effect of acute challenge with 0.2 mg/kg MK-801 or saline on open field behaviour, social interaction, and prepulse inhibition of startle (PPI). Acute BHB administration dose-dependently increased BHB plasma levels, whereas the 2 mmol/kg dose increased plasma glucose levels. The highest acute dose of BHB supressed spontaneous locomotor activity, MK-801-induced locomotor hyperactivity and MK-801-induced disruption of PPI. Chronic BHB treatment normalized MK-801-induced hyperlocomotion, reduction of sociability, and disruption of PPI. In conclusion, BHB may present a novel treatment option for patients with schizophrenia by providing an alternative fuel source to normalize impaired glucose metabolism in the brain.
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.SCHRES.2019.08.002
Abstract: We used the acute NMDA receptor hypoactivity model of schizophrenia in mice to compare the efficacy of a long-term ketogenic diet and a commonly used antipsychotic, olanzapine, and to explore the interaction between these treatments. We found that a ketogenic diet in female mice was as effective as olanzapine to diminish MK-801-induced disruption of prepulse inhibition (PPI). Furthermore, combination of the diet with olanzapine treatment resulted in a similar effect compared to either treatment alone. These results suggest that ketogenic diet can be used effectively together with antipsychotics drugs over an extended period.
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.NEUBIOREV.2016.05.027
Abstract: The cortisol awakening response (CAR), defined as the increase in cortisol release in response to waking up, shows associations with social and environmental risk factors of schizophrenia and has been studied as a potential biomarker in schizophrenia. We report a systematic review and meta-analysis of 11 studies and 879 participants focusing on the CAR of patients with schizophrenia, first-episode psychosis, and at-risk mental states. Random-effects meta-analysis showed that CAR is attenuated in patients with psychosis compared to healthy controls (g=-0.426, 95% CI -0.585 to -0.267, p<0.001, 11 between-group comparisons, n=879). Subgroup analysis showed flattened CAR in patients with schizophrenia (g=-0.556, 95% CI -1.069 to -0.044, p<0.05, 2 between-group comparisons, n=114) and first-episode psychosis (g=-0.544, 95% CI -0.731 to -0.358, p<0.001, 6 between-group comparisons, n=505), but not in in iduals with at-risk mental states. These distinctive alterations of hypothalamic-pituitary-adrenal axis function may have important implications for CAR as a marker for transition risk. However, the lack of objective verification of s ling adherence in these studies may limit the interpretation of the results.
Publisher: Oxford University Press (OUP)
Date: 15-02-2018
Abstract: Helminth infections in children are associated with impaired cognitive development however, the biological mechanisms for this remain unclear. Using a murine model of gastrointestinal helminth infection, we demonstrate that early-life exposure to helminths promotes local and systemic inflammatory responses and transient changes in the gastrointestinal microbiome. Behavioral and cognitive analyses performed 9-months postinfection revealed deficits in spatial recognition memory and an anxiety-like behavioral phenotype in worm-infected mice, which was associated with neuropathology and increased microglial activation within the brain. This study demonstrates a previously unrecognized mechanism through which helminth infections may influence cognitive function, via perturbations in the gut-immune-brain axis.
Publisher: Elsevier BV
Date: 2021
DOI: 10.1016/J.PSYNEUEN.2020.104903
Abstract: Cortisol is the primary glucocorticoid produced by the activation of the hypothalamic pituitary adrenal (HPA) axis after a psychological or physiological stressor. The dysregulation of the HPA axis by chronic stress has been associated with psychiatric disorders. Although hair is currently the main validated source of chronic cortisol concentrations, cortisol is also bound to human nails, another keratinised matrix. Therefore, nail cortisol has the potential to be an alternative retrospective chronic measure of HPA activation. The aim of this systematic review was to assess the temporal resolution, methodological issues, HPA correlates, and target populations in nail cortisol investigations. A qualitative synthesis was performed to assess current literature exploring cortisol concentrations from human nails. A total of 18 eligible human studies extracted from Medline (PubMed and Ovid), ProQuest (PsycINFO), and Scopus found that immunoassays and mass spectrometry were the two primarily methods of analysis. However, methodological variability remained evident between studies. Nail cortisol correlated with saliva and hair in some studies and was investigated across multiple developmental periods. Finally, when applied as an outcome measure in health disorders, higher nail cortisol concentrations have been shown to be associated with acute coronary syndrome and depression. In conclusion, nail cortisol may serve as a retrospective biomarker of chronic stress however, the ability to track how much cortisol is accumulating within nail clippings is complex and may represent a large timespan. Further, very few studies have reported effect sizes and investigated the effects of covariates, such as age, sex, ethnicity, and nail characteristics, which limits the validation of this measure. Further studies are required to validate the utility of nail cortisol as a biomarker of chronic stress across the human lifespan.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Ann-Katrin Kraeuter.