20 research outputs found
Alcohol-Related Context Modulates Performance of Social Drinkers in a Visual Go/No-Go Task: A Preliminary Assessment of Event-Related Potentials
Background Increased alcohol cue-reactivity and altered inhibitory processing have been reported in heavy social drinkers and alcohol-dependent patients, and are associated with relapse. In social drinkers, these two processes have been usually studied separately by recording event-related potentials (ERPs) during rapid picture presentation. The aim of our study was to confront social drinkers to a task triggering high alcohol cue-reactivity, to verify whether it specifically altered inhibitory performance, by using long-lasting background picture presentation. Methods ERP were recorded during visual Go/No-Go tasks performed by social drinkers, in which a frequent Go signal (letter âMâ), and a rare No-Go signal (letter âWâ) were superimposed on three different types of background pictures: neutral (black background), alcohol-related and non alcohol-related. Results Our data suggested that heavy social drinkers made more commission errors than light drinkers, but only in the alcohol-related context. Neurophysiologically, this was reflected by a delayed No-Go P3 component. Conclusions Elevated alcohol cue-reactivity may lead to poorer inhibitory performance in heavy social drinkers, and may be considered as an important vulnerability factor in developing alcohol misuse. Prevention programs should be designed to decrease the high arousal of alcohol stimuli and strengthen cognitive control in young, at-risk individuals.This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.SCOPUS: ar.jinfo:eu-repo/semantics/publishe
Correction: Lesion of the subiculum reduces the spread of amyloid beta pathology to interconnected brain regions in a mouse model of Alzheimerâs disease
Rasagiline Ameliorates Olfactory Deficits in an Alpha-Synuclein Mouse Model of Parkinson's Disease
<div><p>Impaired olfaction is an early pre-motor symptom of Parkinson's disease. The neuropathology underlying olfactory dysfunction in Parkinson's disease is unknown, however α-synuclein accumulation/aggregation and altered neurogenesis might play a role. We characterized olfactory deficits in a transgenic mouse model of Parkinson's disease expressing human wild-type α-synuclein under the control of the mouse α-synuclein promoter. Preliminary clinical observations suggest that rasagiline, a monoamine oxidase-B inhibitor, improves olfaction in Parkinson's disease. We therefore examined whether rasagiline ameliorates olfactory deficits in this Parkinson's disease model and investigated the role of olfactory bulb neurogenesis. α-Synuclein mice were progressively impaired in their ability to detect odors, to discriminate between odors, and exhibited alterations in short-term olfactory memory. Rasagiline treatment rescued odor detection and odor discrimination abilities. However, rasagiline did not affect short-term olfactory memory. Finally, olfactory changes were not coupled to alterations in olfactory bulb neurogenesis. We conclude that rasagiline reverses select olfactory deficits in a transgenic mouse model of Parkinson's disease. The findings correlate with preliminary clinical observations suggesting that rasagiline ameliorates olfactory deficits in Parkinson's disease.</p> </div
Olfactory deficits are age-dependent. A-C: Odor detection test.
<p>Description of the protocol consisting of 2 sessions (S). <b>B.</b> Percentage of time spent sniffing the odor at the concentration of 1â¶10<sup>6</sup> (session 1). WT mice aged 3, 11 and 18 months could detect the odor and the percentage of time sniffing the odor was significantly different from the chance level (50%) (°°°p<0.001). On the contrary, α-syn mice are progressively impaired in detecting the odor. Whereas at 3 months transgenic mice spent more time sniffing the odor compared to the chance level (p<0.05), from 11 months of age their scores no longer differed from the chance level (p>0.05) and the percentage of time spent by α-syn mice to sniff the odor is significantly different from WT mice (two way ANOVA). Statistics: One-sample t-tests to compare each value to chance level (50%) (°p<0.05, °°°p<0.001). Two-way ANOVA: age, pâ=â0.49, F(2,70)â=â0.71; genotype, p<0.0001, F(1,70)â=â40.21; ageĂgenotype, pâ=â0.016, F(2,70)â=â4.42; Bonferroni post-hoc (***p<0.001). <b>C.</b> Percentage of time spent sniffing the odor at the concentration of 1â¶10<sup>4</sup> (session 2). Both WT and α-syn mice aged 3, 11 and 18 months can detect the odor at the concentration of 1â¶10<sup>4</sup> and their percentage of time sniffing the odor is significantly different from the chance level (°°°p<0.001). Moreover, there is no significant difference between the genotypes (two-way ANOVA p>0.05). Statistics: One-sample t-tests to compare each value to chance level (50%) (°°°p<0.001). Two-way ANOVA: age, pâ=â0.12, F(2,70)â=â2.15; genotype, pâ=â0.83, F(1,70)â=â0.045; ageĂgenotype, pâ=â0.64, F(2,70)â=â0.45. <b>D-F: Short-term olfactory memory test. D.</b> Description of the protocol consisting of 2 sessions (S). <b>E.</b> Session 1 with an inter-trial interval of 60 s. Percentage of time spent sniffing the odor during T2 (trial 2) compared to the total time spent sniffing during both trials. All groups of WT mice aged 3, 11 and 18 months as well as α-syn mice aged 3 and 11 months remember the odor during the 2<sup>nd</sup> exposure and their percentage of time sniffing the odor during T2 is significantly different from the chance level (50%) (°°°p<0.001). However, from 18 months of age, α-syn mice are impaired in remembering the odor during the 2<sup>nd</sup> exposure (one-sample t-test, p>0.05) and the percentage of time spent sniffing the odor during T2 is significantly higher compared to 18 month-old WT mice (two-way ANOVA, p<0.001). Statistics: One-sample t-test to compare each value to chance level (50%) (°°°p<0.001). Two-way ANOVA: age, pâ=â0.0010, F(2,70)â=â7.63; genotype, pâ=â0.0032, F(1,70)â=â9.32, ageĂgenotype, pâ=â0.011, F(2,70)â=â4.78; Bonferroni post-hoc (***p<0.001). <b>F.</b> Session 2 with an inter-trial interval of 120 s. Percentage of time spent sniffing the odor during T2 compared to the total time spent sniffing during both trials. All groups of WT mice aged 3, 11 and 18 months remember the odor during the 2<sup>nd</sup> exposure and their percentage of time spent sniffing the odor during T2 is significantly different from the chance level (one-sample t-tests, °°°p<0.001). On the contrary, α-syn mice aged 3, 11 and 18 months, are all impaired in remembering the odor during the 2<sup>nd</sup> exposure (one-sample t-tests, p>0.05) and the percentage of time spent sniffing the odor during T2 is significantly higher compared to WT mice of the same age (two way ANOVA, *p<0.05, **p<0.01). Statistics: One-sample t-tests to compare each value to chance level (50%) (°°p<0.01, °°°p<0.001). Two-way ANOVA: age, pâ=â0.13, F(2,70)â=â2.12; genotype, p<0.0001, F(1,70)â=â26.86; ageĂgenotype, pâ=â0.53, F(2,70)â=â0.64; Bonferroni post-hoc (*p<0.05, **p<0.01). <b>G-H: Odor discrimination test. G.</b> Description of the protocol consisting of 6 habituation trials and one odor discrimination trial. <b>H.</b> Percentage of time spent sniffing the novel odor. At 3, 11 and 18 months, α-syn mice spend significantly less time compared to age-matched control mice to sniff the novel odor suggesting that they are impaired in their ability to discriminate the novel odor (two-way ANOVA, ***p<0.001). Statistics: Two-way ANOVA: age, pâ=â0.0028, F(2,70)â=â6.42; genotype, p<0.0001, F(1,70)â=â77.78; ageĂgenotype, pâ=â0.077, F(2,70)â=â2.66; Bonferroni post-hoc (***p<0.001). For all tests, Nâ=â14 for group aged 3 and 18 months; Nâ=â10 for group aged 11 months.</p
Overexpression of α-synuclein in the olfactory bulb of the α-syn transgenic mice.
<p>Immunostaining of human wild-type α-synuclein in OB of <b>A.</b> WT mice and <b>B-D.</b> α-syn mice aged 12 months. <b>A-B.</b> Scale bars: 500 ”m. <b>C-D.</b> High magnification of <b>C.</b> the glomerular layer (Gl) and <b>D.</b> the granule cell layer (GCL). Scale bars: 50 ”m. α-Syn mice exhibit high expression of human α-synuclein in the different layers of the OB. α-Synuclein immunoreactivity indicates large profiles (arrows) as well as numerous small α-synuclein immunoreactive puncta (arrow heads).</p
Olfactory deficits in the α-syn mouse model of PD.
<p><b>A-B: </b><b>Odor detection test. A.</b> Description of the protocol composed of 3 sessions (S). In each 5-min session, mice were exposed to 2 cartridges, one filled with water, the other with increasing odor concentrations from 1â¶10<sup>8</sup> to 1â¶10<sup>4</sup>. <b>B.</b> Percentage of time sniffing the odor for the different concentrations. WT mice start detecting the odor at the concentration 1â¶10<sup>6</sup> when percentage of time sniffing the odor is significantly different from the chance level (50%, where mice spent same time sniffing water and odor cartridges) (°°°p<0.001, °°p<0.01, one-sample t-test). α-Syn mice can detect the odor only at 1â¶10<sup>4</sup> (°°°p<0.001, one-sample t-test). At the concentration 1â¶10<sup>6</sup>, α-syn mice are significantly impaired compared to WT. Nâ=â10 for each group aged 10â11 months. Statistics: One-sample t-test to compare each value to chance level (50%), (°°°p<0.001, °°p<0.01). Two-way RM ANOVA: odor concentration, pâ=â0.0001, F(2,36)â=â11.96; genotype, pâ=â0.015, F(1,36)â=â7.2; odor concentrationĂgenotype, pâ=â0.0073, F(2,36)â=â5.65; Bonferroni post-hoc (***p<0.001). <b>C-D: Short-term olfactory memory test. C.</b> Description of the protocol composed of 3 sessions (S). Each session consisted of two 5 min-trials (T) where mice are exposed to a novel odor separated by an increasing inter-trial time (ITI) from 60 s to 120 s. <b>D.</b> Percentage of time sniffing the odor during T2 compared to the total time spent sniffing during both trials. WT mice remember the odor during the 2<sup>nd</sup> exposure for the 3 ITI tested and their percentage of time sniffing the odor during T2 was significantly different from the chance level (50%, where mice spent same time sniffing the odor during T1 and T2) (°°p<0.01, °°°p<0.001, one-sample t-test). By contrast, short-term olfactory memory of α-syn mice was impaired from an ITI of 120 s (p>0.05, one-sample t-test). However, it was significantly different from chance level at 60 s and 90 s (°°°p<0.001 and °p<0.05 respectively, one-sample t-tests). Nâ=â10 for each group aged 10â11 months. Statistics: One-sample t-test to compare each value to chance level (50%), (°°°p<0.001, °°p<0.01, °p<0.05). <b>E-H: Odor discrimination test. E and G:</b> Social odor discrimination test. <b>E.</b> Description of the protocol composed of 6 habituation trials where mice are exposed to a familiar odor (F, odor of the tested mouse); and one odor discrimination trial, where one familiar odor is replaced by a novel odor (N, another mouse's odor). This test was performed with low or high odor intensities (wood blocks impregnated with mouse's odor for 2 or 7 days respectively). Each trial lasted 2 min and was separated by 1 min. <b>G.</b> Percentage of time sniffing novel odor. For both low and high odor intensities, α-syn mice have impaired odor discrimination with the percentage of time sniffing the odor significantly lower than WT. Nâ=â19â21 for each group aged 10â11 months. Statistics: Two-way RM ANOVA: odor intensity, pâ=â0.55, F(1,38)â=â0.37; genotype, p<0.0001, F(1,38)â=â27.1; odor intensityĂgenotype, pâ=â0.63, F(1,38)â=â0.23; Bonferroni post-hoc (***p<0.001). <b>F and H:</b> Non-social odor discrimination test. <b>F.</b> Description of the protocol based on the same principle of the social odor discrimination test but using non-social odors (lemon and lime). In the 8<sup>th</sup> 2 min-trial, an item discrimination trial was added where the usual cartridge, with the novel odor (lime), was replaced by a novel item (a novel type of cartridge associated with the same novel odor, lime). <b>H.</b> Percentage of time sniffing the novel odor during the odor discrimination trial and percentage of time exploring the novel item in the item discrimination trial. α-syn mice had significantly impaired odor discrimination of the social odor. By contrast, the ability to discriminate the novel item was similar between WT and α-syn mice suggesting that the discrimination deficit is specific to olfaction. Statistics: unpaired t-test, non-social odor discrimination p<0.0001, Nâ=â19â21 for each group aged 10â11 months; item discrimination pâ=â0.16, Nâ=â10 for each group aged 10-11 months (***p<0.001).</p
Rasagiline improved some aspects of olfaction in α-syn mice. A. Effect of rasagiline on odor detection deficit in α-syn mice.
<p>Rasagiline rescued the odor detection deficit in α-syn mice. At a concentration of 1â¶10<sup>6</sup>, non-treated α-syn mice do not detect the odor and the percentage of time spent sniffing the odor was close to chance level, whereas rasagiline treated mice were significantly higher than the chance level. Moreover, rasagiline treated mice spent a similar time sniffing the odor compared to control mice. Nâ=â9â10 for each group aged 10â11 months. Statistics: One-sample t-test to compare each value to chance level (50%), (°p<0.05, °°p<0.01, °°°p<0.001). Two-way RM ANOVA: odor concentration, p<0.0001, F(2,66)â=â29; group, pâ=â0.19, F(3,66)â=â1.67; odor concentrationĂgroup, pâ=â0.06, F(6,66)â=â2.12; Bonferroni post-hoc (*p<0.05, **p<0.001). <b>B. Effect of rasagiline on short-term olfactory memory impairment in α-syn mice.</b> For the 120 s-ITI, percentage of time spent sniffing the odor in T2 was not different from chance level for both α-syn mice groups, treated or not treated with rasagiline. Rasagiline did not improve the short-term olfactory memory in α-syn mice. Nâ=â 9â10 for each group aged 10â11 months. Statistics: One-sample t-test compare to chance level (50%), (°p<0.05 and °°°p<0.001). Two-way RM ANOVA: ITI, p<0.0001, F(2,68)â=â15.65; group, pâ=â0.13, F(3,68)â=â2.04; ITIĂgroup, pâ=â0.23, F(6,68)â=â1.39; Bonferroni post-hoc. <b>C. Effect of rasagiline on odor discrimination deficit in α-syn mice.</b> Percentage of time spent sniffing the novel odor of α-syn mice was increased by rasagiline treatment for both intensities of the social odor as well as for the non-social odor. α-Syn mice treated with rasagiline were similar to control mice (p>0.05). Rasagiline rescued the odor discrimination deficit of α-syn mice. Nâ=â 18â21 for each group aged 10â11 months. Statistics for social odor discrimination: Two-way RM ANOVA, odor intensity, pâ=â0.032, F(1,74)â=â4.78; group, p<0.0001, F(3,74)â=â13.3; odor intensityĂgroup, pâ=â0.034, F(3,74)â=â3.04; Bonferroni post-hoc (*p<0.05, **p<0.01, ***p<0.001). Statistics for non-social odor discrimination: one-way ANOVA, p<0.001, F(3,73)â=â18.16; Bonferroni post-hoc (***p<0.001).</p
Behavioral experiments: design and parameters analyzed.
<p><b>A.</b> Experimental design of the behavioral study. <b>B</b>. Olfactory- and control tests and the parameters analyzed from these experiments.</p
Neurogenesis changes are not involved in the olfactory deficit of α-syn mice and rasagiline-induced improvement.
<p><b>A.</b> Quantification of newborn cells in the granule cell layer of the OB. Total number of BrdU positive cells was assessed every sixth section by stereology (counting frame 100 ”mĂ100 ”m; counting grid: 300 ”mĂ300 ”m). No difference between control and α-syn mice as well as no effect of rasagiline treatment was observed. Nâ=â4-6 for each group aged 12 months. Statistic: one-way ANOVA, pâ=â0.66, F(3,14)â=â0.54. <b>B.</b> BrdU staining in the olfactory bulb of WT and α-syn mice. Scale bars: 100 ”m. <b>C. </b>Quantification of newborn neurons in the granule cell layer of the OB. The proportion of BrdU positive cells, which are also NeuN positive, was assessed by confocal microscopy. No difference between control and α-syn mice as well as no effect of rasagiline treatment was observed. On average, we analyzed 100 BrdU-positive cells in each animal, Nâ=â3 mice in each group aged 12 months. Statistic: one-way ANOVA, pâ=â0.61, F(3,8)â=â0.65. <b>D.</b> NeuN (green) and BrdU (red) double staining in the OB. Examples of NeuN-positive/BrdU positive-cells observed in WT and α-syn mice. Scale bars: 55.5 ”m.</p