The Neuropathology and Functional Imaging Core will provide neuropathological and physiological services focused on the evaluation of both patients with myotonic dystrophy and mouse models of the disease. The Neuropathology component will provide neuropathological characterization of patients who have died with myotonic dystrophy types 1 and 2 (DM1 and DM2). The objective is to define the distribution and nature of the neuropathological alterations associated with DM1 and DM2, with a particular emphasis on correlation with antemortem neuroimaging and/or clinical CNS-related deficits in patients who have been studied in Project 3. The Core will aid investigators in Projects 1 and 2 by providing histological services and tissues with a major focus on correlating the neuropathological findings in the transgenic mouse models with those of the corresponding human diseases to understand pathological mechanisms. The Functional Imaging component of the Core will provide functional assessments of the cerebral cortical circuitry in the mouse models developed by Projects 1 and 2 and test in the mouse models for abnormalities identified in DM patients by Project 3. The Core will use optical imaging and single cell electrophysiological recordings to characterize the cerebral cortical circuitry in vivo. As DM patients have exaggerated sensitivity to sedatives and stimulants, the Core will investigate whether cerebral cortical circuits show altered sensitivity to these drugs. Flavoprotein imaging has revealed correlations in the background fluorescence among different regions in the cerebral cortex that can be used to assess functional connectivity. The alterations in white matter integrity and grey matter in DM is likely to result in changes in functional connectivity. Therefore, Core A will also test whether this functional connectivity in the cerebral cortex is abnormal in the DM mouse models. Finally, Projects 1 and 2 are proposing to develop mouse models with the goal of reversing the disease phenotypes. Having defined specific circuit abnormalities in the cerebral cortex, the Core will evaluate if the abnormalities are corrected in these rescue mouse models.

Public Health Relevance

Myotonic dystrophy is a complex neurodegenerative disorder that affects multiple systems in the body. Patients have significant neurological problems. However, there is little known about how the disease affects the central nervous system. This proposal aims to understand the underlying disease mechanisms and the nervous system changes in this poorly understood disorder.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Program Projects (P01)
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National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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University of Florida
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Pletnikova, Olga; Sloane, Kelly L; Renton, Alan E et al. (2014) Hippocampal sclerosis dementia with the C9ORF72 hexanucleotide repeat expansion. Neurobiol Aging 35:2419.e17-21
Mohan, Apoorva; Goodwin, Marianne; Swanson, Maurice S (2014) RNA-protein interactions in unstable microsatellite diseases. Brain Res 1584:3-14
Batra, Ranjan; Charizanis, Konstantinos; Manchanda, Mini et al. (2014) Loss of MBNL leads to disruption of developmentally regulated alternative polyadenylation in RNA-mediated disease. Mol Cell 56:311-22
Cleary, John Douglas; Ranum, Laura P W (2014) Repeat associated non-ATG (RAN) translation: new starts in microsatellite expansion disorders. Curr Opin Genet Dev 26:6-15
Wozniak, Jeffrey R; Mueller, Bryon A; Lim, Kelvin O et al. (2014) Tractography reveals diffuse white matter abnormalities in Myotonic Dystrophy Type 1. J Neurol Sci 341:73-8
Goodwin, Marianne; Swanson, Maurice S (2014) RNA-binding protein misregulation in microsatellite expansion disorders. Adv Exp Med Biol 825:353-88
Hernandez-Hernandez, Oscar; Guiraud-Dogan, Celine; Sicot, Geraldine et al. (2013) Myotonic dystrophy CTG expansion affects synaptic vesicle proteins, neurotransmission and mouse behaviour. Brain 136:957-70
Cramer, Samuel W; Gao, Wangcai; Chen, Gang et al. (2013) Reevaluation of the beam and radial hypotheses of parallel fiber action in the cerebellar cortex. J Neurosci 33:11412-24
Zhang, Chaolin; Lee, Kuang-Yung; Swanson, Maurice S et al. (2013) Prediction of clustered RNA-binding protein motif sites in the mammalian genome. Nucleic Acids Res 41:6793-807
Cleary, John D; Ranum, Laura P W (2013) Repeat-associated non-ATG (RAN) translation in neurological disease. Hum Mol Genet 22:R45-51

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