Journal
BEHAVIOURAL BRAIN RESEARCH
Volume 233, Issue 1, Pages 169-175Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2012.04.051
Keywords
Mucopolysaccharidosis type I; Hang wire; Open field; Gait; Neuroinflammation
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Funding
- Conselho Nacional de Desenvolvimento Cientifico-CNPq
- Fundo de Incentivo a Pesquisa do Hospital de Clinicas de Porto Alegre (FIPE-HCPA)
- National Institutes of Health [DK066448]
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Mucopolysaccharidosis (MPS) type I (Hurler syndrome) is a lysosomal storage disorder characterized by deficiency of alpha-L-iduronidase (IDUA), intracellular storage of glycosaminoglycans (GAGs) and progressive neurological pathology. The MPS I mouse model provides an opportunity to study the pathophysiology of this disorder and to determine the efficacy of novel therapies. Previous work has demonstrated a series of abnormalities in MPS I mice behavior, but so far some important brain functions have not been addressed. Therefore, in the present study we aimed to determine if MPS I mice have motor abnormalities, and at what age they become detectable. MPS I and normal male mice from 2 to 8 months of age were tested in open-field for locomotor activity, hindlimb gait analysis and hang wire performance. We were able to detect a progressive reduction in the crossings and rearings in the open field test and in the hang wire test in MPS I mice from 4 months, as well as a reduction in the gait length at 8 months. Histological examination of 8-month old mice cortex and cerebellum revealed storage of GAGs in Purkinje cells and neuroinflammation, evidenced by GFAP immunostaining. However TUNEL staining was negative, suggesting that death does not occur. Our findings suggest that MPS I mice have a progressive motor dysfunction, which is not caused by loss of neuron cells but might be related to a neuroinflammatory process. (C) 2012 Elsevier B.V. All rights reserved.
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