Maintaining a colony of transgenic rat model of Alzheimer’s disease.

Alzheimer’s disease is a progressive neurodegenerative disease, resulting in gross cognitive dysfunction going hand in hand with widespread cortical cell loss and related loss of connectivity in the brain. The disease begins with mild memory problems, which are followed by a progressive cognitive decline over a period of several years and severe dementia during later disease stages. It is now well substantiated that amyloid expression in AD is not a random process but exhibits a strikingly changing distribution pattern over time, apparently correlated to the changes in severity of the dementia (Thal et al., 2000). This developmental cascade is closely related to the now classical clinical staging for the disease (Braak & Braak 1995). Pathology initially starts in the entorhinal cortex and hippocampus, both structures that are strongly implicated in episodic memory (Scoville & Milner 1957; Eichenbaum et al., 2007). The pathology then progressively involves other portions of the medial temporal lobe, finally spreading throughout the neocortex. Here we request permission to continue the breeding of a transgenic rat as an animal model. The model faithfully mimics the time-dependent increase in amyloid plaque load as well as the typical time-dependent changes in spatial distribution of the amyloid. In order to understand the effects onto neuronal networks we will use functional and connectivity measures. We plan to breed and use animals for our research which is funded by Helse Midt Norge, THON foundation, and a NTNU Enabling Technologies grant. We estimate to breed a total of 800 rats. Animals will be kept till a maximum of 18 months of age, and they rarely show signs of disease symptoms as measured by behavioral parameters. Animals are housed in large, enriched cages and are checked daily by trained animal caretakers. We have a VET employed to check and advice on health and welfare matters. We use transgenic rats to model a human disorder which, as yet cannot be studied in another way. We are in addition aiming to establish cell-cultures to test some parameters, an approach that eventually may result in a reduction of the number or animals used. All experimental procedures are well-established and the experimentalists are trained and licensed. Moreover, regular training updates are required for all personnel involved in animal care and experiments. The use of established and monitored procedures will also reduce the number of animals used in these experiments. The aim will be to use these animals to look for functional and structural alterations related to the development of the disease.