@article{78e75db5a94c4a4aa7794a77a718f96f,
title = "Behavioral deficits, early gliosis, dysmyelination and synaptic dysfunction in a mouse model of mucolipidosis IV",
abstract = "Mucolipidosis IV (MLIV) is caused by mutations in the gene MCOLN1. Patients with MLIV have severe neurologic deficits and very little is known about the brain pathology in this lysosomal disease. Using an accurate mouse model of mucolipidosis IV, we observed early behavioral deficits which were accompanied by activation of microglia and astrocytes. The glial activation that persisted during the course of disease was not accompanied by neuronal loss even at the late stage. In vivo [Ca2+]-imaging revealed no changes in resting [Ca2+] levels in Mcoln1 -/- cortical neurons, implying their physiological health. Despite the absence of neuron loss, we observed alterations in synaptic plasticity, as indicated by elevated paired-pulse facilitation and enhanced long-term potentiation. Myelination deficits and severely dysmorphic corpus callosum were present early and resembled white matter pathology in mucolipidosis IV patients. These results indicate the early involvement of glia, and challenge the traditional view of mucolipidosis IV as an overtly neurodegenerative condition.",
keywords = "Glia, In vivo Ca imaging, Lysosomal storage disease, Mucolipidosis IV, Neuropathology",
author = "Yulia Grishchuk and Sarmi Sri and Nikita Rudinskiy and Weiyuan Ma and Stember, {Katherine G.} and Cottle, {Matthew W.} and Ellen Sapp and Marian Difiglia and Alona Muzikansky and Betensky, {Rebecca A.} and Wong, {Andrew M.S.} and Bacskai, {Brian J.} and Hyman, {Bradley T.} and Kelleher, {Raymond J.} and Cooper, {Jonathan D.} and Slaugenhaupt, {Susan A.}",
note = "Funding Information: We thank Dr. Bhuvarahamurthy Venugopal for assisting with mouse colony maintenance. This work was supported by grants from the Mucolipidosis IV Foundation (to YG and SAS), the William Randolph Hearst foundation (to YG), and the National Institutes of Health, NINDS R01NS039995 (SAS), EB000768 (BJB), S10RR025645 (BJB), and using equipment originally funded by the Batten Disease Support and Research Association (BDSRA), Batten Disease Family Association, and The Natalie Fund. This work was conducted with support from Harvard NeuroDiscovery Center and Harvard Catalyst (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health. Publisher Copyright: {\textcopyright} 2014 Grishchuk et al.; licensee BioMed Central Ltd.",
year = "2014",
month = jan,
day = "27",
doi = "10.1186/s40478-014-0133-7",
language = "English (US)",
volume = "2",
journal = "Acta Neuropathologica Communications",
issn = "2051-5960",
publisher = "BioMed Central",
number = "1",
}