Cytokines, neurotrophins, and oxidative stress in brain disease from mucopolysaccharidosis IIIB

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Abstract
Mucopolysaccharidosis IIIB (MPS IIIB; Sanfilippo syndrome type B) is characterized by profound neurological deterioration. Because a murine model of MPS IIIB disease is available, we focused on analysis of gene expression in the brain and cerebellum of 7‐month‐old MPS IIIB mice by pathway‐specific filter microarrays designed to probe apoptotic‐related, neurotrophic signalling molecules and inflammatory cytokines and receptors. Moreover, we extended the analysis with real‐time PCR performed at 1, 3, 7 months after birth. Bdnf was down‐regulated in the brain but up‐regulated in the cerebellum at 7 months of age, both at RNA and at protein levels. Cbln1 presented a threefold increase in the oldest brains while remaining unaltered in the cerebellum. Ccl3, Casp11, gp91phox, p67phox, and p47phox showed an increased expression in both brain and cerebellum at each examined time point. Ccl3, in particular, exhibited in both organs and at all times tested approximately a tenfold increase in its expression. Insofar as p47phox, p67phox, and gp91phox are all components of the phagocyte NADPH oxidase, our results suggest the possible involvement of the reactive oxygen species in the genesis of neurodegeneration in MPS IIIB disease.

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