TY - THES ID - 135539382 TI - Psychopathological behaviour in relationship to environmental stress in an alpha-mannosidosis mouse model and evaluation of enzyme replacement therapy AU - Bernaerts, Sylvie AU - Stroobants, Stijn AU - KU Leuven. Faculteit Psychologie en Pedagogische Wetenschappen. Opleiding Master in de psychologie PY - 2015 PB - Leuven : KU Leuven. Faculteit Psychologie en Pedagogische Wetenschappen DB - UniCat UR - https://www.unicat.be/uniCat?func=search&query=sysid:135539382 AB - Alpha-mannosidosis is a rare lysosomal storage disease caused by lysosomal α-mannosidase deficiency. In human patients the disease is characterized by an array of physical and physiological symptoms as well as psychiatric disease. This master thesis will focus on the psychiatric symptoms. Patients may show recurrent episodes of confusion and psychosis, delusions, auditory and visual hallucinations, anxiety and depression. In addition, these symptoms are often preceded by a physical or psychological stressor. A mouse model of alpha-mannosidosis was created that mimicked the human features of the milder form of this disease. However, psychopathological behaviour alterations in this mouse model have not been described elaborately yet, nor has the influence of environmental stress been assessed in this mouse model of alpha-mannosidosis. Therefore, the goal of this master thesis is to make up a psychopathological behaviour profile of alpha-mannosidosis mice and assess its relationship to environmental stress. In addition, as the efficacy of enzyme replacement therapy for the correction of storage in alpha-mannosidosis has been proved in several animal studies of alpha-mannosidosis mice, a second objective is to assess the effects of enzyme replacement therapy on psychopathological behaviour in these alpha-mannosidosis mice. Two groups of alpha-mannosidase knock-out mice and control mice were used. The first group comprised an experimental group of 17 4-to-5-month-old alpha-mannosidosis mice and a control group of 17 age-matched control mice. Before these mice were assessed in a behavioural test battery, a genotype mixed group of 17 out of these 34 mice underwent a stress conditioning procedure in order to elicit chronic stress. Then, all mice were assessed in a comprehensive behavioural test battery comprised of seven behavioural paradigms, including depression, anxiety, explorative behaviour, sensorimotor gating, social exploration and working memory tests. Prepulse inhibition test was used to assess sensorimotor gating deficiency. Amphetamine provocation test investigated reaction to a psychostimulant. Open field considered exploratory behaviour and elevated plus maze assessed anxiety-related behaviour. Sucrose preference test and tail suspension test were employed to assess depression-related behaviour. Lastly, sociability/preference for social novelty (SPSN) test was used to assess autism-related behaviour in mice. Afterwards, 17 non-stressed mice were used for further testing, namely assessment of short-term enzyme replacement therapy via open field test, SPSN test and amphetamine provocation test. Moreover, another group of 32 alpha-mannosidosis mice and control mice were tested for the assessment of long-term enzyme replacement therapy via open field test and amphetamine provocation test. Test results were analysed using analysis of variance and Student's t-tests. Behaviour resembling the psychiatric symptoms in human patients was not found in present study. Gene x environmental stress interaction could not be confirmed, except in amphetamine provocation test, and enzyme replacement therapy did not reveal behavioural changes in alpha-mannosidosis mice either. Differences in symptoms between alpha-mannosidosis mice and human patients might be due to the younger age of mice. In addition, stress conditioning procedure might not have succeeded. ER -