Olfactory deficits in mice overexpressing human wildtype -synuclein

Autor:	Eliezer Masliah, Nicole A. Tetreault, Marie-Françoise Chesselet, Caitlin K. Mulligan, C.B. Hutson, Sheila M. Fleming
Rok vydání:	2008
Předmět:	Male Olfactory system Parkinson's disease Mice Transgenic Olfaction Biology Neuroprotection Article Mice Discrimination Psychological medicine Animals Humans Habituation Habituation Psychophysiologic Appetitive Behavior General Neuroscience Age Factors Brain Parkinson Disease medicine.disease Immunohistochemistry Olfactory Bulb Corpus Striatum Olfactory bulb Smell Substantia Nigra medicine.anatomical_structure nervous system Odor Peripheral nervous system Sensation Disorders alpha-Synuclein Neuroscience
Zdroj:	European Journal of Neuroscience. 28:247-256
ISSN:	1460-9568 0953-816X
Popis:	Accumulation of alpha-synuclein in neurons of the central and peripheral nervous system is a hallmark of sporadic Parkinson's disease (PD) and mutations that increase alpha-synuclein levels cause familial PD. Transgenic mice overexpressing alpha-synuclein under the Thy1 promoter (Thy1-aSyn) have high levels of alpha-synuclein expression throughout the brain but no loss of nigrostriatal dopamine neurons up to 8 months, suggesting that they may be useful to model pre-clinical stages of PD. Olfactory dysfunction often precedes the onset of the cardinal motor symptoms of PD by several years and includes deficits in odor detection, discrimination and identification. In the present study, we measured olfactory function in 3- and 9-month-old male Thy1-aSyn mice with a buried pellet test based on latency to find an exposed or hidden odorant, a block test based on exposure to self and non-self odors, and a habituation/dishabituation test based on exposure to non-social odors. In a separate group of mice, alpha-synuclein immunoreactivity was assessed in the olfactory bulb. Compared with wildtype littermates, Thy1-aSyn mice could still detect and habituate to odors but showed olfactory impairments in aspects of all three testing paradigms. Thy1-aSyn mice also displayed proteinase K-resistant alpha-synuclein inclusions throughout the olfactory bulb. These data indicate that overexpression of alpha-synuclein is sufficient to cause olfactory deficits in mice similar to that observed in patients with PD. Furthermore, the buried pellet and block tests provided sufficient power for the detection of a 50% drug effect, indicating their usefulness for testing novel neuroprotective therapies.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d931a027b1e5734601c71d6f925d45fa https://doi.org/10.1111/j.1460-9568.2008.06346.x Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.