Quantification of the light microscopic analyzes after anti-tyrosine hydroxylase (TH) staining of the olfactory bulb (OB) and the striatal fibers.

<p>No significant differences were seen 2, 5 and 20 days after intranasal application of 0.5(p>0.05, n = 3, striatal fibers were analyzed in a field of 45×45 µm, TH positive neurons were manually counted in the glomerular layer of the OB (total magnification 200×)). Error bars represent SEM.</p

Olfaction in Three Genetic and Two MPTP-Induced Parkinson’s Disease Mouse Models

<div><p>Various genetic or toxin-induced mouse models are frequently used for investigation of early PD pathology. Although olfactory impairment is known to precede motor symptoms by years, it is not known whether it is caused by impairments in the brain, the olfactory epithelium, or both. In this study, we investigated the olfactory function in three genetic Parkinson’s disease (PD) mouse models and mice treated with MPTP intraperitoneally and intranasally. To investigate olfactory function, we performed electro-olfactogram recordings (EOGs) and an olfactory behavior test (cookie-finding test). We show that neither a parkin knockout mouse strain, nor intraperitoneal MPTP treated animals display any olfactory impairment in EOG recordings and the applied behavior test. We also found no difference in the responses of the olfactory epithelium to odorants in a mouse strain over-expressing doubly mutated α-synuclein, while this mouse strain was not suitable to test olfaction in a cookie-finding test as it displays a mobility impairment. A transgenic mouse expressing mutated α-synuclein in dopaminergic neurons performed equal to control animals in the cookie-finding test. Further we show that intranasal MPTP application can cause functional damage of the olfactory epithelium.</p></div

EOG recordings and cookie-finding tests after intranasal (IN) MPTP application.

<p>(<b>A</b>) Olfactory epithelium after intranasal application of 5 µl blue dye. EOGs were measured in the indicated areas of the OE. (<b>B</b>) EOG data from mice treated wit 0.5 mg/nostril MPTP intranasally. The amplitude was significantly reduced in MPTP treated wildtype (p<0.01), and BAsyn animals (p<0.05), while the rise and the decay time of the responses did not differ (n_MPTP = 6, n_saline = 10). (<b>C</b>) After the training day (day 4), wildtype mice treated IN with MPTP treated took significantly longer to find the cookie 5 days (p<0.01) and 6 days (p<0.05) after MPTP application (n = 10 for each condition), compared to control animals. Finding time of BAsyn mice was not increased after IN MPTP treatment. (<b>D</b>) Animal mobility (mean movement velocity) during the cookie-finding test. Data is normalized to the wild type animals. No significant difference was detectable between saline and MPTP treated animals. BAsyn mice display a significantly reduced mobility (p<0.01). Error bars represent SEM.</p

TH immunostainings of the olfactory bulb and striatum after intranasal MPTP administration.

<p>Light microscopic analysis after anti-tyrosine hydroxylase (TH) staining of the olfactory bulb (OB) and the striatum of BAsyn and wild type mice. Mice were investigated 2, 5 or 20 days (d) after intranasal (IN) MPTP treatment with 0.5 mg/nostril. Scale bars: 50 µm. Pictures are representatives of three biological replicates.</p

EOG recordings and cookie-finding tests of different mouse strains.

<p>(<b>A</b>) EOG recordings from PaKO and BAsyn mice at 5 months (5 m) and 8 months (8 m) of age. Black and white bars represent the mouse lines listed on the left. n_Parkin = 6, n_BAsyn5m = 5, n_BAsyn8m = 6, n_controls = n_transgenic. Five different dilutions [c] of Henkel 100 were applied (100 ms duration). No significant differences could be detected. (<b>B</b>) Normalized EOG recordings (n = 4) after single odorant applications (geraniol 1∶10, vanillin 40 mM, phenylethylamine (PEA) 1∶1000). Error bars represent SEM. (<b>C</b>) Performances of different mouse lines in the cookie-finding test. Data was normalized to wild type animals and depicts latency to find the cookie. BAsyn mice (8 m) took significantly longer to find the cookie. n_Parkin = 10 (p = 0.75), n_BAsyn = 12 (p = 0.04), n_ThSyn = 10 (p = 0.91), n_controls = n_transgenic. Error bars represent SEM.</p

Olfaction in three genetic and two MPTP-induced Parkinson's disease mouse models

Various genetic or toxin-induced mouse models are frequently used for investigation of early PD pathology. Although olfactory impairment is known to precede motor symptoms by years, it is not known whether it is caused by impairments in the brain, the olfactory epithelium, or both. In this study, we investigated the olfactory function in three genetic Parkinson's disease (PD) mouse models and mice treated with MPTP intraperitoneally and intranasally. To investigate olfactory function, we performed electro-olfactogram recordings (EOGs) and an olfactory behavior test (cookie-finding test). We show that neither a parkin knockout mouse strain, nor intraperitoneal MPTP treated animals display any olfactory impairment in EOG recordings and the applied behavior test. We also found no difference in the responses of the olfactory epithelium to odorants in a mouse strain over-expressing doubly mutated $\alpha$-synuclein, while this mouse strain was not suitable to test olfaction in a cookie-finding test as it displays a mobility impairment. A transgenic mouse expressing mutated $\alpha$-synuclein in dopaminergic neurons performed equal to control animals in the cookie-finding test. Further we show that intranasal MPTP application can cause functional damage of the olfactory epithelium

EOG recordings and cookie-finding tests of intraperitoneally (IP) MPTP injected animals.

<p>EOG data from mice injected with MPTP intraperitoneally (<b>A</b>) two days (2d) and (<b>B</b>) five days (5d) after treatment. The amplitudes of the responses, the rise, and the decay times did not differ significantly between the groups. n_IP = 5 animals per condition. (<b>C</b>) Cookie-finding tests after 5 days of IP MPTP injection showed no significant difference between saline and MPTP treated animals (n = 10 per condition). BAsyn animals took significantly longer to find the cookie. (<b>D</b>) Animal mobility (mean movement velocity) during the cookie-finding test. BAsyn animals display a significantly reduced mobility. Error bars represent SEM.</p