Browsing
     by title


0-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

or enter first few letters:   
OK
Full Text
Peer Reviewed
See detailNAD(P)HX dehydratase (NAXD) deficiency: a novel neurodegenerative disorder exacerbated by febrile illnesses
Van Bergen, Nicole; Guo, Yiran; Rankin, Julia et al

in Brain: a Journal of Neurology (2019), 142(1), 50-58

Physical stress, including high temperatures, may damage the central metabolic nicotinamide nucleotide cofactors [NAD(P)H], generating toxic derivatives [NAD(P)HX]. The highly conserved enzyme NAD(P)HX ... [more ▼]

Physical stress, including high temperatures, may damage the central metabolic nicotinamide nucleotide cofactors [NAD(P)H], generating toxic derivatives [NAD(P)HX]. The highly conserved enzyme NAD(P)HX dehydratase (NAXD) is essential for intracellular repair of NAD(P)HX. Here we present a series of infants and children who suffered episodes of febrile illness-induced neurodegeneration or cardiac failure and early death. Whole-exome or whole-genome sequencing identified recessive NAXD variants in each case. Variants were predicted to be potentially deleterious through in silico analysis. Reverse-transcription PCR confirmed altered splicing in one case. Subject fibroblasts showed highly elevated concentrations of the damaged cofactors S-NADHX, R-NADHX and cyclic NADHX. NADHX accumulation was abrogated by lentiviral transduction of subject cells with wild-type NAXD. Subject fibroblasts and muscle biopsies showed impaired mitochondrial function, higher sensitivity to metabolic stress in media containing galactose and azide, but not glucose, and decreased mitochondrial reactive oxygen species production. Recombinant NAXD protein harbouring two missense variants leading to the amino acid changes p.(Gly63Ser) and p.(Arg608Cys) were thermolabile and showed a decrease in Vmax and increase in KM for the ATP-dependent NADHX dehydratase activity. This is the first study to identify pathogenic variants in NAXD and to link deficient NADHX repair with mitochondrial dysfunction. The results show that NAXD deficiency can be classified as a metabolite repair disorder in which accumulation of damaged metabolites likely triggers devastating effects in tissues such as the brain and the heart, eventually leading to early childhood death. [less ▲]

Detailed reference viewed: 209 (46 UL)
Full Text
Peer Reviewed
See detailA narrative review of psychological and educational strategies applied to young children's eating behaviours aimed at reducing obesity risk
Gibson, E. Leigh; Wildgruber, Andreas; Kreichauf, Susanne et al

in Obesity Reviews : An Official Journal of the International Association for the Study of Obesity (2012), 13(Suppl 1), 85-95

Strategies to reduce risk of obesity by influencing preschool children’s eating behaviour are reviewed. The studies are placed in the context of relevant psychological processes, including inherited and ... [more ▼]

Strategies to reduce risk of obesity by influencing preschool children’s eating behaviour are reviewed. The studies are placed in the context of relevant psychological processes, including inherited and acquired preferences, and behavioural traits, such as food neophobia, ‘enjoyment of food’ and ‘satiety responsiveness’. These are important influences on how children respond to feeding practices, as well as predictors of obesity risk. Nevertheless, in young children, food environment and experience are especially important for establishing eating habits and food preferences. Providing information to parents, or to children, on healthy feeding is insufficient. Acceptance of healthy foods can be encouraged by 5-10 repeated tastes. Recent evidence suggests rewarding healthy eating can be successful, even for verbal praise alone, but that palatable foods should not be used as rewards for eating. Intake of healthier foods can be promoted by increasing portion size, especially in the beginning of the meal. Parental strategies of pressuring to eat and restriction do not appear to be causally linked to obesity, but are instead primarily responses to children’s eating tendencies and weight. Moderate rather than frequent restriction may improve healthy eating in children. Actively positive social modelling by adults and peers can be effective in encouraging healthier eating. [less ▲]

Detailed reference viewed: 140 (0 UL)
Full Text
Peer Reviewed
See detailThe negative affect repair questionnaire: factor analysis and psychometric evaluation in three samples
Scherer, Anne; Eberle, Nicole; Boecker, Maren et al

in BMC Psychiatry (2013), 13(1), 16

Negative affect and difficulties in its regulation have been connected to several adverse psychological consequences. While several questionnaires exist, it would be important to have a theory-based ... [more ▼]

Negative affect and difficulties in its regulation have been connected to several adverse psychological consequences. While several questionnaires exist, it would be important to have a theory-based measure that includes clinically relevant items and shows good psychometric properties in healthy and patient samples. This study aims at developing such a questionnaire, combining the two Gross [1] scales Reappraisal and Suppression with an additional response-focused scale called Externalizing Behavioral Strategies covering clinically relevant items. The samples consisted of 684 students (mean age = 23.3, SD = 3.5; 53.6% female) and 369 persons with mixed mental disorders (mean age = 36.0 SD = 14.6; 71.2% female). Items for the questionnaire were derived from existing questionnaires and additional items were formulated based on suggestions by clinical experts. All items start with ―When I don’t feel well, in order to feel better...‖. Participants rated how frequently they used each strategy on a 5-point Likert scale. Confirmatory Factor Analyses were conducted to verify the factor structure in two separate student samples and a clinical sample. Group comparisons and correlations with other questionnaires were calculated to ensure validity. After modification, the CFA showed good model fit in all three samples. Reliability scores (Cronbach’s α) for the three NARQ scales ranged between .71 and .80. Comparisons between students and persons with mental disorders showed the postulated relationships, as did comparisons between male and female students and persons with or without Borderline Personality Disorder. Correlations with other questionnaires suggest the NARQ’s construct validity. The results indicate that the NARQ is a psychometrically sound and reliable measure with practical use for therapy planning and tracking of treatment outcome across time. We advocate the integration of the new response-focused strategy in the Gross’s model of emotion regulation. [less ▲]

Detailed reference viewed: 115 (3 UL)
Full Text
Peer Reviewed
See detailNegotiating the precautionary principle: Regulatory and institutional roots of divergent US and EU positions
König, Ariane UL

in International Journal of BioTechnology (2002), 4(1), 61-81

The precautionary principle has been a bone of contention in international negotiations on the governance of environmental and health risks. The US administration and European institutions often present ... [more ▼]

The precautionary principle has been a bone of contention in international negotiations on the governance of environmental and health risks. The US administration and European institutions often present opposing views on whether formal references to precaution help or hinder the global governance of risk, in particular where linked to world trade. The European Commission official position, backed by Council, Parliament and some Member States, advocates the principle's use in legal texts and pushes for the elaboration of international guidelines for its application. The proposed guidelines, whilst explicitly conforming to basic principles of trade law, include recommendations on broad socio-economic impact analyses of alternative risk mitigation measures and emphasise political aspects of decisions on risk. The US administration's official position papers oppose references to precaution and socio-economic impact analysis in international laws and guidelines on risk analysis. They mainly cite fears of abuse of the concept as guise for protectionist measures. In each administration a wide range of state and non-state actors with disparate views inform policy makers who then have to adopt one coherent position. This article suggests that overarching differences in the negotiating positions adopted by the US and European institutions, often attributed to culturally and politically rooted biases on risk and uncertainty, are also reflected in institutional practices and regulatory frameworks of the two jurisdictions. It recommends taking disparate institutional structures and regulatory frameworks into account in future deliberations on international guidelines on risk analysis. [less ▲]

Detailed reference viewed: 117 (5 UL)
Full Text
Peer Reviewed
See detailNetwork analysis of neurodegenerative disease highlights a role of toll-like receptor signaling
Nguyen, Thanh-Phuong UL; Caberlotto, Laura; Morine, Melissa J. et al

in BioMed Research International (2014), 2014

Despite significant advances in the study of the molecular mechanisms altered in the development and progression of neurodegenerative diseases (NDs), the etiology is still enigmatic and the distinctions ... [more ▼]

Despite significant advances in the study of the molecular mechanisms altered in the development and progression of neurodegenerative diseases (NDs), the etiology is still enigmatic and the distinctions between diseases are not always entirely clear. We present an efficient computationalmethod based on protein-protein interaction network (PPI) tomodel the functional network of NDs. The aim of this work is fourfold: (i) reconstruction of a PPI network relating to the NDs, (ii) construction of an association network between diseases based on proximity in the disease PPI network, (iii) quantification of disease associations, and (iv) inference of potentialmolecularmechanisminvolved in the diseases.The functional links of diseases not only showed overlap with the traditional classification in clinical settings, but also offered new insight into connections between diseases with limited clinical overlap. To gain an expanded view of the molecular mechanisms involved in NDs, both direct and indirect connector proteins were investigated. The method uncovered molecular relationships that are in common apparently distinct diseases and provided important insight into the molecular networks implicated in disease pathogenesis. In particular, the current analysis highlighted the Toll-like receptor signaling pathway as a potential candidate pathway to be targeted by therapy in neurodegeneration. [less ▲]

Detailed reference viewed: 84 (10 UL)
Full Text
Peer Reviewed
See detailNeurological Diseases from a Systems Medicine Point of View.
Ostaszewski, Marek UL; Skupin, Alexander UL; Balling, Rudi UL

in Methods in molecular biology (Clifton, N.J.) (2016), 1386

The difficulty to understand, diagnose, and treat neurological disorders stems from the great complexity of the central nervous system on different levels of physiological granularity. The individual ... [more ▼]

The difficulty to understand, diagnose, and treat neurological disorders stems from the great complexity of the central nervous system on different levels of physiological granularity. The individual components, their interactions, and dynamics involved in brain development and function can be represented as molecular, cellular, or functional networks, where diseases are perturbations of networks. These networks can become a useful research tool in investigating neurological disorders if they are properly tailored to reflect corresponding mechanisms. Here, we review approaches to construct networks specific for neurological disorders describing disease-related pathology on different scales: the molecular, cellular, and brain level. We also briefly discuss cross-scale network analysis as a necessary integrator of these scales. [less ▲]

Detailed reference viewed: 280 (8 UL)
Full Text
Peer Reviewed
See detailNeuromuscular correlates of subthalamic stimulation and upper limb freezing in Parkinson's disease.
Scholten, M.; Klotz, R.; Plewnia, C. et al

in Clinical Neurophysiology (2016)

OBJECTIVE: The pathophysiology of deep brain stimulation mechanisms and resistant freezing phenomena in idiopathic Parkinson's disease (iPD) remains incompletely understood. Further studies on the ... [more ▼]

OBJECTIVE: The pathophysiology of deep brain stimulation mechanisms and resistant freezing phenomena in idiopathic Parkinson's disease (iPD) remains incompletely understood. Further studies on the neuromuscular substrates are needed. METHODS: We analyzed 16 patients with advanced iPD and bilateral subthalamic nucleus stimulation, and 13 age- and gender-matched healthy controls. Patients were tested after overnight withdrawal of medication with 'stimulation off' (StimOff) and 'stimulation on' (StimOn). Subjects performed continuous tapping of the right index finger with simultaneous recordings of biomechanical registration, EMG of finger flexors and extensors, and EEG. First, we analyzed EEG and EMG spectral measures comparing StimOff with healthy controls and StimOff with StimOn (irrespective of freezing). Second, we contrasted 'regular (unimpaired) tapping' and 'freezing' resistant to subthalamic neurostimulation as obtained in StimOn. RESULTS: iPD showed increased intermuscular coherence around 8Hz in StimOff that was reduced in StimOn. This 8Hz muscular activity was not coherent to cortical activity. 'Freezing' episodes showed increased muscle activity of finger flexors and extensors at 6-9Hz, and increased cortical activity at 7-11Hz. During transition from regular tapping to 'freezing' the cortical activity first increased over the left sensorimotor area followed by a spread to the left frontal and right parietal areas. CONCLUSIONS: We identified neuromuscular motor network features of subthalamic neurostimulation therapy and resistant upper limb freezing that point to increased low-frequency muscular and cortical activity. SIGNIFICANCE: Together, our findings demonstrate several motor network abnormalities associated with upper limb freezing that may translate into future research on freezing of gait in iPD. [less ▲]

Detailed reference viewed: 158 (13 UL)
Full Text
Peer Reviewed
See detailNeuronal nitric oxide synthase signaling in the heart is regulated by the sarcolemmal calcium pump 4b.
Oceandy, Delvac; Cartwright, Elizabeth J.; Emerson, Michael et al

in Circulation (2007), 115(4), 483-92

BACKGROUND: Neuronal nitric oxide synthase (nNOS) has recently been shown to be a major regulator of cardiac contractility. In a cellular system, we have previously shown that nNOS is regulated by the ... [more ▼]

BACKGROUND: Neuronal nitric oxide synthase (nNOS) has recently been shown to be a major regulator of cardiac contractility. In a cellular system, we have previously shown that nNOS is regulated by the isoform 4b of plasma membrane calcium/calmodulin-dependent ATPase (PMCA4b) through direct interaction mediated by a PDZ domain (PSD 95, Drosophilia Discs large protein and Zona occludens-1) on nNOS and a cognate ligand on PMCA4b. It remains unknown, however, whether this interaction has physiological relevance in the heart in vivo. METHODS AND RESULTS: We generated 2 strains of transgenic mice overexpressing either human PMCA4b or PMCA ct120 in the heart. PMCA ct120 is a highly active mutant form of the pump that does not interact with or modulate nNOS function. Calcium was extruded normally from PMCA4b-overexpressing cardiomyocytes, but in vivo, overexpression of PMCA4b reduced the beta-adrenergic contractile response. This attenuated response was not observed in ct120 transgenic mice. Treatment with a specific nNOS inhibitor (N omega-propyl-L-arginine) reduced the beta-adrenergic response in wild-type and ct120 transgenic mice to levels comparable to those of PMCA4b transgenic animals. No differences in lusitropic response were observed in either transgenic strain compared with wild-type littermates. CONCLUSIONS: These data demonstrate the physiological relevance of the interaction between PMCA4b and nNOS and suggests its signaling role in the heart. [less ▲]

Detailed reference viewed: 97 (0 UL)
Peer Reviewed
See detailNeuropathie
De Beaufort, Carine UL

in Bougnères, P.F.; Jos, J.; Chaussain, J.L. (Eds.) Le diabète de l'enfant (1990)

Detailed reference viewed: 30 (0 UL)
Full Text
Peer Reviewed
See detailNeuropsychiatric Complications of Efavirenz Therapy: Suggestions for a New Research Paradigm
Sütterlin, Stefan UL; Vögele, Claus UL; Gauggel, Siegfried

in Journal of Neuropsychiatry and Clinical Neurosciences (The) (2010), 22

This review gives an up-to-date account of the current state of research on neuropsychiatric complications associated with efavirenz therapy and critiques the methods used in previous studies. The authors ... [more ▼]

This review gives an up-to-date account of the current state of research on neuropsychiatric complications associated with efavirenz therapy and critiques the methods used in previous studies. The authors suggest an extension of current research strategies using psychophysiological concepts and including behavioral regulation models. From a practical perspective, these may contribute to better screening methods for the identification of those at risk for neuropsychiatric complications and the improvement of neuropsychiatric monitoring during efavirenz treatment. From a theoretical viewpoint, the suggested research paradigms may help to move beyond the current state of descriptive approaches and thus improve our limited understanding of underlying mechanisms. [less ▲]

Detailed reference viewed: 123 (1 UL)
Full Text
Peer Reviewed
See detailNew cultural competences needed for healthcare teams as a priority in treatment of chronic diseases
Odero, Angela UL; Baumann, Michèle UL

in "Health Psychology across the Lifespan: Uniting Research, Practice and Policy” (2018)

Technological changes and higher prevalence of chronic diseases require changing patients’ and healthcare professionals’ position with more participation in healthcare organization, and more implication ... [more ▼]

Technological changes and higher prevalence of chronic diseases require changing patients’ and healthcare professionals’ position with more participation in healthcare organization, and more implication in their relationships. Based on the Canadian ‘patient-as-partner in healthcare’ approach, our aims were to identify and categorize cultural values underlying this term in Luxembourg, and to characterize a set of cultural competencies needed for its practical application. Method: A qualitative study using a semi-directive guide developed within an INTERREG project was conducted among 30 healthcare professionals. A categorical thematic content analysis was realized using N'Vivo software. Results: For some professionals, the word ‘partner’ is not appropriate in Luxembourgish, but they defined it as a companion who engages in a mutual cooperation, structured collaboration and sharing of information with a common goal: Quality of healthcare. For others, a ‘partner’ is an associate who takes part in decision making, discussions, negotiations and evaluations. This partner approach would allow processes of change, bringing autonomy (surveillance, self-education, and monitoring treatment) to the patients, provided that professionals partly cede their traditional power. Trust and respect would be the main start of this process. Difficulties in communication and relationships would arise when helping the patients understand their disease, adhering to instructions, and giving a balanced place to the information found on Internet. Conclusion: This ‘collaborative accompaniment’ appears to allow decisional balance, an interdisciplinary method which requires training for all partners (physicians GP or specialists, patients and psychologist) and not only case-managers to help patients acquire self-efficacy for behavioral changes. [less ▲]

Detailed reference viewed: 151 (2 UL)
Full Text
Peer Reviewed
See detailNew definition for the partial remission period in children and adolescents with type 1 diabetes
Mortensen, H. B.; Hougaard, P.; Swift, P. et al

in Diabetes Care (2009), 32(8), 1384-1390

OBJECTIVE - To find a simple definition of partial remission in type 1 diabetes that reflects both residual β-cell function and efficacy of insulin treatment. RESEARCH DESIGN AND METHODS - A total of 275 ... [more ▼]

OBJECTIVE - To find a simple definition of partial remission in type 1 diabetes that reflects both residual β-cell function and efficacy of insulin treatment. RESEARCH DESIGN AND METHODS - A total of 275 patients aged <16 years were followed from onset of type 1 diabetes. After 1, 6, and 12 months, stimulated C-peptide during a challenge was used as a measure of residual β-cell function. RESULTS - By multiple regression analysis, a negative association between stimulated C-peptide and A1C (regression coefficient -0.21, P < 0.001) and insulin dose (-0.94, P < 0.001) was shown. These results suggested the definition of an insulin dose-adjusted A1C (IDAA1C) as A1C (percent) + [4 × insulin dose (units per kilogram per 24 h)]. A calculated IDAA1C ≤9 corresponding to a predicted stimulated C-peptide >300 pmol/l was used to define partial remission. The IDAA1C ≤9 had a significantly higher agreement (P < 0.001) with residual β-cell function than use of a definition of A1C ≤7.5%. Between 6 and 12 months after diagnosis, for IDAA1C ≤9 only 1 patient entered partial remission and 61 patients ended partial remission, for A1C ≤7.5% 15 patients entered partial remission and 53 ended, for a definition of insulin dose ≤0.5 units · kg-1 · 24 h-1 5 patients entered partial remission and 66 ended, and for stimulated C-peptide (>300 pmol/l) 9 patients entered partial remission and 49 ended. IDAA1C at 6 months has good predictive power for stimulated C-peptide concentrations after both 6 and 12 months. CONCLUSIONS - A new definition of partial remission is proposed, including both glycemic control and insulin dose. It reflects residual β-cell function and has better stability compared with the conventional definitions. © 2009 by the American Diabetes Association. [less ▲]

Detailed reference viewed: 117 (1 UL)
Full Text
Peer Reviewed
See detailNew domains of health capability of family caregivers: An exploratory study using the grounded theory.
Bucki, Barbara; Baumann, Michèle UL

in Pascara, Clara (Ed.) Clinical Psychology (2015)

Increased life expectancy, a declining economic growth, and the management of chronic diseases call for inter-generational solidarity but undermine the physical and psychological health of family ... [more ▼]

Increased life expectancy, a declining economic growth, and the management of chronic diseases call for inter-generational solidarity but undermine the physical and psychological health of family caregivers. Their health capability has already been studied through eight domains: physical and psychological functioning, lifestyle value, self-efficacy towards health services, family support, social capital, socioeconomic conditions and access to health services. Our aim was to identify new domains. Methods: A grounded theory method was applied. Family caregivers of stroke victims living at home were recruited in the Lorraine region (France; n=8) and Luxembourg (n=6). Semi-structured interviews were led face-to-face about their health status, how they currently take care of their health, and what internal resources they need to achieve optimal health. Verbatim were open-coded and grouped to form new domains of health capability. Items reflecting the main idea of the categories were formulated. Throughout the analyses, a control process was applied. Items were validated by consensus with an expert group. Results: Seven women and seven men (age 63.6±10.1) participated. Seven new domains emerged: health knowledge, health self-efficacy, health value, life skills, health decision-making, motivation, and attitude towards the future. 76 items were generated: 51 reflected generic abilities while 26 were specific to family caregiving. Discussion: Content analysis of these domains is highly instructive. First, it allows guiding the preparation of innovative supports to promote health capability, and second, this list can serve as a basis to elaborate a guide to which clinicians can refer to orient family caregivers according to their needs. [less ▲]

Detailed reference viewed: 112 (3 UL)
Peer Reviewed
See detailNew hepatic fat activates PPARalpha to maintain glucose, lipid, and cholesterol homeostasis
Chakravarthy, M. V.; Pan, Z.; Zhu, Y. et al

in Cell Metabolism (2005), 1(5), 309-22

De novo lipogenesis is an energy-expensive process whose role in adult mammals is poorly understood. We generated mice with liver-specific inactivation of fatty-acid synthase (FAS), a key lipogenic enzyme ... [more ▼]

De novo lipogenesis is an energy-expensive process whose role in adult mammals is poorly understood. We generated mice with liver-specific inactivation of fatty-acid synthase (FAS), a key lipogenic enzyme. On a zero-fat diet, FASKOL (FAS knockout in liver) mice developed hypoglycemia and fatty liver, which were reversed with dietary fat. These phenotypes were also observed after prolonged fasting, similarly to fasted PPARalpha-deficiency mice. Hypoglycemia, fatty liver, and defects in expression of PPARalpha target genes in FASKOL mice were corrected with a PPARalpha agonist. On either zero-fat or chow diet, FASKOL mice had low serum and hepatic cholesterol levels with elevated SREBP-2, decreased HMG-CoA reductase expression, and decreased cholesterol biosynthesis; these were also corrected with a PPARalpha agonist. These results suggest that products of the FAS reaction regulate glucose, lipid, and cholesterol metabolism by serving as endogenous activators of distinct physiological pools of PPARalpha in adult liver [less ▲]

Detailed reference viewed: 74 (0 UL)
Full Text
Peer Reviewed
See detailA new rechargeable device for deep brain stimulation: a prospective patient satisfaction survey.
Timmermann, Lars; Schupbach, Michael; Hertel, Frank UL et al

in European neurology (2013), 69(4), 193-9

BACKGROUND: Deep brain stimulation (DBS) is highly successful in treating Parkinson's disease (PD), dystonia, and essential tremor (ET). Until recently implantable neurostimulators were nonrechargeable ... [more ▼]

BACKGROUND: Deep brain stimulation (DBS) is highly successful in treating Parkinson's disease (PD), dystonia, and essential tremor (ET). Until recently implantable neurostimulators were nonrechargeable, battery-driven devices, with a lifetime of about 3-5 years. This relatively short duration causes problems for patients (e.g. programming and device-use limitations, unpredictable expiration, surgeries to replace depleted batteries). Additionally, these batteries (relatively large with considerable weight) may cause discomfort. To overcome these issues, the first rechargeable DBS device was introduced: smaller, lighter and intended to function for 9 years. METHODS: Of 35 patients implanted with the rechargeable device, 21 (including 8 PD, 10 dystonia, 2 ET) were followed before and 3 months after surgery and completed a systematic survey of satisfaction with the rechargeable device. RESULTS: Overall patient satisfaction was high (83.3 +/- 18.3). Dystonia patients tended to have lower satisfaction values for fit and comfort of the system than PD patients. Age was significantly negatively correlated with satisfaction regarding process of battery recharging. CONCLUSIONS: Dystonia patients (generally high-energy consumption, severe problems at the DBS device end-of-life) are good, reliable candidates for a rechargeable DBS system. In PD, younger patients, without signs of dementia and good technical understanding, might have highest benefit. [less ▲]

Detailed reference viewed: 140 (4 UL)
Full Text
Peer Reviewed
See detailA new synuclein-transgenic mouse model for early Parkinson's reveals molecular features of preclinical disease
Hendrickx, Diana M.; Garcia, Pierre; Ashrafi, Amer et al

in Molecular Neurobiology (in press)

Understanding Parkinson’s disease (PD) in particular in its earliest phases, is important for diagnosis and treatment. However, human brain samples are collected post- mortem, reflecting mainly end stage ... [more ▼]

Understanding Parkinson’s disease (PD) in particular in its earliest phases, is important for diagnosis and treatment. However, human brain samples are collected post- mortem, reflecting mainly end stage disease. Because brain samples of mouse models can be collected at any stage of the disease process, they are useful to investigate PD progression. Here, we compare ventral midbrain transcriptomics profiles from α- synuclein transgenic mice with a progressive, early PD-like striatal neurodegeneration across different ages using pathway, gene set and network analysis methods. Our study uncovers statistically significant altered genes across ages and between genotypes with known, suspected, or unknown function in PD pathogenesis and key pathways associated with disease progression. Among those are genotype-dependent alterations associated with synaptic plasticity, neurotransmission, as well as mitochondria-related genes and dysregulation of lipid metabolism. Age-dependent changes were among others observed in neuronal and synaptic activity, calcium homeostasis, and membrane receptor signaling pathways, many of which linked to G- protein coupled receptors. Most importantly, most changes occurred before neurodegeneration was detected in this model, which points to a sequence of gene expression events that may be relevant for disease initiation and progression. It is tempting to speculate that molecular changes similar to those changes observed in our model happen in midbrain dopaminergic neurons before they start to degenerate. In other words, we believe we have uncovered molecular changes that accompany the progression from preclinical to early PD. [less ▲]

Detailed reference viewed: 137 (3 UL)
Peer Reviewed
See detailNicotinamid
De Beaufort, Carine UL

in Diabetes, prevention and therapy (1992), 6

Detailed reference viewed: 25 (0 UL)
Peer Reviewed
See detailNicotine Interact With Gabaergic System: Behavioural Evidences?,
Mancuso, Giovanna UL; Tirelli, Ezio

in Pflügers Archiv : European Journal of Physiology (1996), 431(3),

Detailed reference viewed: 26 (1 UL)
Peer Reviewed
See detail[Nifedipine in hypertensive emergencies and severe hypertension].
Groth, H.; Foerster, E. C.; Neyses, Ludwig UL et al

in Schweizerische Rundschau fur Medizin Praxis = Revue suisse de medecine Praxis (1984), 73(2), 45-9

Detailed reference viewed: 89 (0 UL)