title: Behavioral deficits and cholinergic pathway abnormalities in male Sanfilippo B mice.
abstract: Sanfilippo B syndrome is a progressive neurological disorder caused by inability to catabolize heparan sulfate glycosaminoglycans. We studied neurobehavior in male Sanfilippo B mice and heterozygous littermate controls from 16 to 20 weeks of age. Affected mice showed reduced anxiety, with a decrease in the number of stretch-attend postures during the elevated plus maze (p=0.001) and an increased tendency to linger in the center of an open field (p=0.032). Water maze testing showed impaired spatial learning, with reduced preference for the target quadrant (p=0.01). In radial arm maze testing, affected mice failed to achieve above-chance performance in a win-shift working memory task (t-test relative to 50% chance: p=0.289), relative to controls (p=0.037). We found a 12.4% reduction in mean acetylcholinesterase activity (p<0.001) and no difference in choline acetyltransferase activity or acetylcholine in whole brain of affected male animals compared to controls. Cholinergic pathways are affected in adult-onset dementias, including Alzheimer disease. Our results suggest that male Sanfilippo B mice display neurobehavioral deficits at a relatively early age, and that as in adult dementias, they may display deficits in cholinergic pathways.
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Kan
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
authors.forename: Steven Q
authors.initials: SQ
authors.lastname: Le
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
authors.forename: Quang D
authors.initials: QD
authors.lastname: Bui
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
authors.forename: Braeden
authors.initials: B
authors.lastname: Benedict
authors.affiliation: Department of Psychology, Behavioral Testing Core, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Jesse
authors.initials: J
authors.lastname: Cushman
authors.affiliation: Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sands
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA. Electronic address: pdickson@labiomed.org.
authors.forename: Patricia I
authors.initials: PI
authors.lastname: Dickson
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001007:Anxiety; D001921:Brain / Q000201:enzymology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D005239:Fear; D008124:Locomotion; D008297:Male; D008570:Memory, Short-Term; D051379:Mice; D008810:Mice, Inbred C57BL; D009084:Mucopolysaccharidosis III / Q000201:enzymology* / Q000523:psychology*; D045442:Rotarod Performance Test; D065853:Spatial Learning
chemical_list: D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D000109:Acetylcholine
keywords: Acetylcholinesterase; Glycosaminoglycan; Inborn error of metabolism; Lysosomal; Mucopolysaccharidosis; Neurodegeneration