ABSTRACT
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). There is increasing evidence that MS is not only characterized by immune mediated inflammatory reactions, but also by neurodegenerative processes. There is cumulating evidence that neurodegenerative processes, for example mitochondrial dysfunction, oxidative stress, and glutamate (Glu) excitotoxicity, seem to play an important role in the pathogenesis of MS. The alteration of mitochondrial homeostasis leads to the formation of excitotoxins and redox disturbances. Mitochondrial dysfunction (energy disposal failure, apoptosis, etc.), redox disturbances (oxidative stress and enhanced reactive oxygen and nitrogen species production), and excitotoxicity (Glu mediated toxicity) may play an important role in the progression of the disease, causing axonal and neuronal damage. This review focuses on the mechanisms of mitochondrial dysfunction (including mitochondrial DNA (mtDNA) defects and mitochondrial structural/functional changes), oxidative stress (including reactive oxygen and nitric species), and excitotoxicity that are involved in MS and also discusses the potential targets and tools for therapeutic approaches in the future.
Subject(s)
Mitochondria/metabolism , Multiple Sclerosis/metabolism , Neurotoxins/metabolism , Oxidation-Reduction , Animals , Biomarkers , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/pathology , Disease Models, Animal , Disease Progression , Glutamic Acid/metabolism , Humans , Multiple Sclerosis/etiology , Multiple Sclerosis/pathology , Multiple Sclerosis/therapy , Oxidative Stress , Receptors, Glutamate/metabolismABSTRACT
Huntington's disease is an autosomal dominant inherited disorder, caused by an expanded polyglutamine region of a protein called huntingtin with unknown function. Transgenic mice expressing the N-terminal of huntingtin, containing 82 glutamines, exhibit a progressive disorder, which resembles to the human disease. In this study, we tested the longitudinal behaviour changes in this transgenic line in open-field and elevated-plus-maze tests. The motor performance deteriorated at 12 weeks of age and the disease progressed as indicated by the decreased total distance covered, the decreased mean velocity and the decreased exploratory behaviour. The level of anxiety was unchanged in transgenic mice as compared with their littermate controls. The motor deterioration was similar to that in other Huntington's disease models, while the level of anxiety was different. These tests are suitable means of following the progression of the disease and useful for studies of the effects of therapeutic interventions.
Subject(s)
Behavior, Animal/physiology , Exploratory Behavior/physiology , Huntington Disease/physiopathology , Motor Skills/physiology , Animals , Anxiety/genetics , Anxiety/metabolism , Disease Models, Animal , Grooming/physiology , Humans , Huntingtin Protein , Huntington Disease/genetics , Immobility Response, Tonic/physiology , Male , Mice , Mice, Transgenic , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Rotarod Performance Test , Stereotyped Behavior/physiologyABSTRACT
INTRODUCTION: The screening and recognition of dementing disorders are considered as important tasks of general practitioners. Despite of the recent progress made in the treatment of cognitive, behavioral symptoms and slowing down the rate of progression, difficulties are still existing in the early detection, and the most frequent dementia forms such as Alzheimer's disease (AD) and vascular dementia (VD) are underdiagnosed in Hungary. Any rapid, easy-to-use dementia screening method therefore could be of great value in the community. AIMS: The Hungarian standardisation of a new dementia screening tool, the 7 Minute Test (7MT) has been reported here. Accuracy, sensitivity and specificity were calculated. The authors provide new data regarding the discriminative power of this test in a variety of dementing and dementia related conditions. METHODS: The test results of 339 probands, referred to the local memory clinic, were evaluated in all subtests, where orientation in time, memory, verbal fluency, and visuoconstructive skills are assessed. The patients were clustered into seven groups according to their clinical diagnosis, such as: Control (CNT), Mild Cognitive Impairment (MCI), AD, VD, mixed AD-VD, depression (D) and Organic Amnestic Syndrome (OAS). RESULTS: In overall, the test successfully discriminated 77% of the CNT and all disease cases (sensitivity 85%, specificity 55%). When the AD and CNT groups were compared separately, the highest values: 91% sensitivity, 86% specificity have been found. A total score of 139 has been suggested as a cutoff value to separate CNT and dementia cases. These results suggest that the test is suitable to classify CNT and "real" dementia cases (AD, VD, mixed AD-VD), but not valid within the real dementia groups. Furthermore, it is not helpful for the identification of MCI, pseudodementia cases (D) and OAS as well. CONCLUSION: The 7MT could be a valuable dementia screening tool in the primary care, but it is not specific for any form of dementia.
