Faktorer som regulerer aquaporin-ekspresjonen i hjernen
1 Formål
Our laboratory focuses on the role of aquaporin water channels. Aquaporin-4 (AQP4) is the predominant brain water channel, and is important for brain water homeostasis and transport of solutes. In this project we want to investigate if AQP4 may be under circadian control and if the level of expression and polarization is day/night-alternating.
2 Skadevirkninger
The experiments cause very little harm. Changing day/night cycle might give mild stress for a few days. During the terminal experiments the animals are deeply anesthetized with a ZRF-cocktail and feels no pain. During housing the experienced staff in the animal facility uses scoring sheet (attachment) for evaluation of pain and definition of human endpoint.
3 Forventet nytteverdi
AQP4 points to serving an important role in several neurodegenerative diseases such as Alzheimers and Parkinsons disease. Sleep disruption is often correlated with neurodegenerative diseases. This project will give important clues to understanding what mechanisms regulate the expression of Aqp4 and if the regulation depends on the sleep/wake states. It will provide us with important knowledge on the mechanisms by which Aqp4 contributes to neurodegenerative diseases.
4 Antall dyr og art
We will use mostly C57/BL6 mice and some AQP4 KO mice for control. The AQP4-KO animals lack the water channel molecule AQP4 which plays an important role in water and volume homeostasis in the brain and other organs such as muscle, heart and kidney. We will need a total of 61 mice. 51 C57/BL6 and 10 AQP4 KO.
5 Hvordan etterleve 3R
The main part of the animals will be purchased commercially with no need for breeding. We will do the main part of the experiments ex vivo. To reduce usage we will accompany with other in vitro experiments. We reduce to minimum number of animals for quantitative results.
Our laboratory focuses on the role of aquaporin water channels. Aquaporin-4 (AQP4) is the predominant brain water channel, and is important for brain water homeostasis and transport of solutes. In this project we want to investigate if AQP4 may be under circadian control and if the level of expression and polarization is day/night-alternating.
2 Skadevirkninger
The experiments cause very little harm. Changing day/night cycle might give mild stress for a few days. During the terminal experiments the animals are deeply anesthetized with a ZRF-cocktail and feels no pain. During housing the experienced staff in the animal facility uses scoring sheet (attachment) for evaluation of pain and definition of human endpoint.
3 Forventet nytteverdi
AQP4 points to serving an important role in several neurodegenerative diseases such as Alzheimers and Parkinsons disease. Sleep disruption is often correlated with neurodegenerative diseases. This project will give important clues to understanding what mechanisms regulate the expression of Aqp4 and if the regulation depends on the sleep/wake states. It will provide us with important knowledge on the mechanisms by which Aqp4 contributes to neurodegenerative diseases.
4 Antall dyr og art
We will use mostly C57/BL6 mice and some AQP4 KO mice for control. The AQP4-KO animals lack the water channel molecule AQP4 which plays an important role in water and volume homeostasis in the brain and other organs such as muscle, heart and kidney. We will need a total of 61 mice. 51 C57/BL6 and 10 AQP4 KO.
5 Hvordan etterleve 3R
The main part of the animals will be purchased commercially with no need for breeding. We will do the main part of the experiments ex vivo. To reduce usage we will accompany with other in vitro experiments. We reduce to minimum number of animals for quantitative results.