Object recognition as a measure of memory in 1-2 years old transgenic minipigs carrying the APPsw mutation for Alzheimer's disease.

Alzheimer's disease (AD) is a disabling, fatal disease, where animal models potentially can enable investigation of aetiology and treatment. The first litter of Göttingen minipigs carrying a mutation for human AD was born in 2007, showing transgene expression. In human AD patients, memory impairment is the most striking and consistent feature. The aim of the present study was to examine effects of the APPsw transgene on memory of AD minipigs compared with non-transgenic controls at two ages (1-2 years) using the spontaneous object recognition test (SORT), which is based on behavioural discrimination of familiar and novel objects. No significant difference between AD minipigs and controls was found when comparing object recognition as a measure of memory. The minipigs did explore the novel object significantly more than the familiar, indicating the expected recognition of the familiar object. Two different inter-phase intervals were used (IPI: 10-40 min). For both ages, object recognition was evident using 10 min IPI. When using 40 min IPI, object recognition was evident only at age 1 year. Comparing memory of a relatively small group of AD minipigs and controls at two rather young ages using the SORT, we were not able to show memory impairment in APPsw carrying minipigs. Being an age-dependent disease, the transgene is expected to cause AD-like symptoms in this porcine model, and the SORT should be repeated at older ages.

Determination of odor detection threshold in the Gottingen minipig.

The aim of the study was to examine the ability of Göttingen minipigs to acquire an olfaction-based operant conditioning task and to determine the detection threshold for ethyl acetate and ethanol. We used an automated olfactometer developed for rodents to train and test 14 pigs. Odor sampling and reliable responding were obtained after three to fifteen 160-trial sessions. Successful transfer of the task from ethyl acetate to ethanol was achieved in 1-4 sessions. Detection threshold for ethyl acetate varied between 10(-2)% and 10(-6)% v/v and for ethanol between 0.1% and 5 × 10(-6)% v/v. The results provide evidence that minipigs can successfully acquire 2-odorant discrimination using a food-rewarded instrumental conditioning paradigm for testing olfactory function. This olfactory discrimination paradigm provides reliable measures of olfactory sensitivity and thereby enables detection of changes in olfaction in a porcine model of Alzheimer's disease currently being developed.