Altered olfactory function in the MRL model of CNS lupus.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that damages several bodily systems, including the CNS. Brain atrophy and diverse neuropsychiatric manifestations are common and serious complications of SLE. Recently, it has been reported that many patients with CNS involvement also present with olfactory deficits of unknown etiology. Similar to CNS SLE, spontaneous development of lupus-like disease in MRL/lpr mice is accompanied by neurodegeneration in periventricular regions and a constellation of behavioral deficits dependent on olfaction. To test the possibility that olfactory dysfunction also occurs in autoimmune mice, we presently examine odor-guided behaviors using a battery of paradigms. Indeed, lupus-prone males spent less time exploring unfamiliar conspecifics and demonstrated age-dependant performance deficits when exposed to low concentrations of attractant and repellant odors. The emergence of olfactory changes was associated with a skewed distribution of DCX(+) cells in the proximal portion of the rostral migratory stream (RMS). The present results are consistent with the hypothesis that the onset of a SLE-like condition affects periventricular regions, including the RMS, as evidenced by disrupted migration of neuronal precursor cells toward the olfactory bulb. If so, ensuing hyposmia and/or olfactory memory deficit may contribute to altered performance in other behavioral tasks and reflect a prodrome of brain damage induced by chronic autoimmune disease.
The Brain-Body Institute, St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
Minesh
M
Kapadia
Mile
M
Stanojcic
Aoife M
AM
Earls
Sheena
S
Pulapaka
Jennifer
J
Lee
Boris
B
Sakic
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004192:Discrimination, Psychological / Q000502:physiology; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005106:Exploratory Behavior; D005247:Feeding Behavior; D020945:Lupus Vasculitis, Central Nervous System / Q000150:complications*; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D009812:Odorants; D000857:Olfaction Disorders / Q000209:etiology* / Q000473:pathology; D009833:Olfactory Pathways / Q000378:metabolism; D011930:Reaction Time; D012903:Smell / Q000502:physiology*; D012919:Social Behavior
C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides