Behavioural Phenotyping of APPswe/PS1δE9 Mice: Age-Rrelated Changes and Effect of Long-Term Paroxetine Treatment.

Alzheimer's disease (AD) is a devastating illness characterized by a progressive loss of cognitive, social, and emotional functions, including memory impairments and more global cognitive deficits. Clinical-epidemiological evidence suggests that neuropsychiatric symptoms precede the onset of cognitive symptoms both in humans with early and late onset AD. The behavioural profile promoted by the AD pathology is believed to associate with degeneration of the serotonergic system. Using the APPswe/PS1δE9 model of AD-like pathology starting with 9 months old mice, we characterised long term non-cognitive behavioural changes measured at 9, 12, 15, and 18 months of age and applied principal component analysis on data obtained from open field, elevated plus maze, and social interaction tests. Long-term treatment with the selective serotonin reuptake inhibitor (SSRI) paroxetine was applied to assess the role of 5-HT on the behavioural profile; duration of treatment was 9 months, initiated when mice were 9 months of age. Treatment with paroxetine delays the decline in locomotion, in exploration and risk assessment behaviour, found in the APP/PS1 mice. APP/PS1 mice also exhibit low social activity and less aggressiveness, both of which are not affected by treatment with paroxetine. The APP/PS1 behavioural phenotype, demonstrated in this study, only begins to manifest itself from 12 months of age. Our results indicate that treatment with SSRI might ameliorate some of the behavioural deficits found in aged APP/PS1 mice

A Placement for Everyone

‘A Placement for Everyone’ outlines an emergent project in which staff and students collaborate to envision a transformation in their university/art school. Rather than convey pre-existing knowledge and expertise from tutor to students, we are working together as equal but different participants in a reflexive experiment with the institutional conditions and social purpose of learning. A primary influence has been the Artist Placement Group (APG), which from 1966—1979 negotiated for artists to be placed in business, industry and governmental organizations. These placements were not framed as commissions or contracts between the artist and the host, but were developed around the APG concept of ‘the open brief’, with no prescriptions, and no outcomes agreed in advance. In December 2012, I designated my academic post at University of the Arts London (UAL) as an artist’s placement, with a remit to promote creative engagement with the ecological and social-economic crisis. I aimed to connect artistic research with pedagogy, by involving staff and students in aligning our university’s operations with its stated values

Abbreviation of behavioural variables scored during testing.

<p>Abbreviation of behavioural variables scored during testing.</p

Effect of age, genotype and treatment on social interaction, tested on two consecutive days, analysed by principal component analysis.

<p>Factor scores for 4 types of behaviour (principal components) are shown in A-D. MANOVA was used to analyse significance in effect of age, genotype and treatment, following by Fisher’s LSD <i>post hoc</i> test for group-wise comparisons: *, **, ***—p < 0.05, 0.01, 0.001 correspond to differences in factor scores between groups at 9, 12, 15 or 18 months of age; +, ++, +++—p < 0.05, 0.01, and 0.001 correspond to age-effect within groups compared to factor scores at 9 months; ¤, ¤¤, ¤¤¤—p < 0.05, 0.01, 0.001 correspond to intra-group comparisons of factor scores at 12 months. Bars indicate Means ± SEM Black bars, Wt (n = 15–23); white bars, Tg (n = 12–22); dark grey bars, Wt-paroxetine treated (n = 14–16); light grey bars, Tg-paroxetine treated (n = 7–12, and n = 3 at 12 months of age). 9, 12, 15 and 18 months of age correspond to 0, 3, 6 and 9 months of treatment, respectively.</p

Effect of age, genotype and treatment on performance in OF (open field) and EPM (elevated plus maze) tests, analysed by principal component analysis.

<p>Factor scores for 4 types of behaviour (principal components) are shown in A-D. MANOVA was used to analyse significance in effect of age, genotype and treatment, followed by Fisher’s LSD <i>post hoc</i> test for group-wise comparisons: *, **, ***—p < 0.05, 0.01, 0.001 correspond to differences in factor scores between groups at 9, 12, 15 or 18 months of age; <b>+, ++, +++—</b>p < 0.05, 0.01, and 0.001 correspond to age-effect within groups compared to factor scores at 9 months; ¤, ¤¤, ¤¤¤—p < 0.05, 0.01, 0.001 correspond to intra-group comparisons of factor scores at 12 months. Bars indicate Means ± SEM Black bars, Wt (n = 14–15); white bars, Tg (n = 12–13); dark grey bars, Wt-paroxetine treated (n = 14–16); light grey bars, Tg-paroxetine treated (n = 6–12, and n = 4 at 12 months of age). 9, 12, 15 and 18 months of age correspond to 0, 3, 6 and 9 months of treatment, respectively.</p

The serum paroxetine levels assessed by UHPLC-MS/MS.

<p>The serum paroxetine levels assessed by UHPLC-MS/MS.</p