The anatomical changes responsible for narcolepsy remain unknown. While receptor abnormalities have been identified, it is unclear if these are the sole or major cause of the disease. The hypothesis to be tested in this project, is that narcolepsy is due to a localizable degenerative neuropathology that occurs prior to, or at the time of symptom onset. Using age and breed matched narcoleptic and control dogs, we will: l. Quantify the changes in the volume of a number of brainstem and forebrain nuclei to identify regional degeneration in narcolepsy. 2. Look for the expression of immediate early genes (IEG'S) (c-jun,jun-D and c-fos) prior to the onset of narcoleptic symptoms. Certain IEG's (c- jun and jun-D) have been shown to be expressed for prolonged periods during neuronal degeneration. 3. Use cupric silver staining technique to locate axonal degeneration. We will also use complementary histological stains (Hematoxylin-eosin and glial fibrillary acidic protein [GFAP]) to determine the nature of any localized or diffuse degeneration in narcolepsy. In pilot studies for this proposal using silver staining, we have found consistent and massive degeneration in certain limbic nuclei. specific to the narcoleptic dog. This finding encourages us to believe that we will be able to identify a localized neuropathology underlying this disease. However, even if the proposed volume, IEG and axonal degeneration studies are negative, these studies will be important in eliminating several major hypotheses of the etiology of narcolepsy.
| Bonvalet, Melodie; Ollila, Hanna M; Ambati, Aditya et al. (2017) Autoimmunity in narcolepsy. Curr Opin Pulm Med 23:522-529 |
| Plante, David T; Finn, Laurel A; Hagen, Erika W et al. (2016) Subjective and Objective Measures of Hypersomnolence Demonstrate Divergent Associations with Depression among Participants in the Wisconsin Sleep Cohort Study. J Clin Sleep Med 12:571-8 |
| Gottlieb, D J; Hek, K; Chen, T-H et al. (2015) Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study. Mol Psychiatry 20:1232-9 |
| Ollila, Hanna M; Ravel, Jean-Marie; Han, Fang et al. (2015) HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy. Am J Hum Genet 96:136-46 |
| Li, Jason; Moore 4th, Hyatt; Lin, Ling et al. (2015) Association of low ferritin with PLM in the Wisconsin Sleep Cohort. Sleep Med 16:1413-1418 |
| Kornum, Birgitte Rahbek; Pizza, Fabio; Knudsen, Stine et al. (2015) Cerebrospinal fluid cytokine levels in type 1 narcolepsy patients very close to onset. Brain Behav Immun 49:54-8 |
| Kawai, Makoto; O'Hara, Ruth; Einen, Mali et al. (2015) Narcolepsy in African Americans. Sleep 38:1673-81 |
| Holm, Anja; Lin, Ling; Faraco, Juliette et al. (2015) EIF3G is associated with narcolepsy across ethnicities. Eur J Hum Genet 23:1573-80 |
| Jacob, Louis; Leib, Ryan; Ollila, Hanna M et al. (2015) Comparison of Pandemrix and Arepanrix, two pH1N1 AS03-adjuvanted vaccines differentially associated with narcolepsy development. Brain Behav Immun 47:44-57 |
| de Lecea, Luis (2015) Optogenetic control of hypocretin (orexin) neurons and arousal circuits. Curr Top Behav Neurosci 25:367-78 |
Showing the most recent 10 out of 55 publications
