Olfactory abnormalities in Huntington's disease: decreased plasticity in the primary olfactory cortex of R6/1 transgenic mice and reduced olfactory discrimination in patients.
Reduced neuronal plasticity in the striatum, hippocampus, and neocortex is a common feature of transgenic mouse models of Huntington's disease (HD). Doublecortin (DCX) and polysialylated neural cell adhesion molecule (PSA-NCAM) are associated with structural plasticity in the adult mammalian brain, are markers of newly formed neurons in the dentate gyrus of the adult hippocampus, and are highly expressed in primary olfactory (piriform) cortex. Animal studies have demonstrated that a reduction in plasticity in the piriform cortex is associated with a selective impairment in odour discrimination. Therefore, the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex were quantified as measures of plasticity in early stage (fifteen week old) R6/1 transgenic HD mice. The transgenic mice had a large reduction in the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex, similar to that previously reported in the R6/2 mice. We also tested whether odour discrimination, as well as identification and detection, were impaired in HD patients and found that patients (at a similar disease stage as the mice) had an impairment in odour discrimination and identification, but not odour detection. These results suggest that olfactory impairments observed in HD patients may be the result of reduced plasticity in the primary olfactory cortex.
Lazic
Stanley E
SE
Centre for Brain Repair, University of Cambridge, CB2 2PY, UK. stan.lazic@cantab.net
Goodman
Anna O G
AO
Grote
Helen E
HE
Blakemore
Colin
C
Morton
A Jennifer
AJ
Hannan
Anthony J
AJ
van Dellen
Anton
A
Barker
Roger A
RA
D000818:Animals; D016022:Case-Control Studies; D004192:Discrimination, Psychological / Q000502:physiology*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D000857:Olfaction Disorders / Q000209:etiology* / Q000473:pathology; D009833:Olfactory Pathways / Q000473:pathology*; D012794:Sialic Acids / Q000378:metabolism; D018709:Statistics, Nonparametric
C000714328:DCX protein, human; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; D009479:Neuropeptides; D009687:Nuclear Proteins; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule