Employees – University of Copenhagen

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Department of Drug Design and Pharmacology > Employees

Caroline Marie Voss

Caroline Marie Voss

PhD fellow

My project is concerned with brain energy metabolism in astrocytes when AMP-activated protein kinase (AMPK) is activated. AMPK has been described as the master metabolic switch in various cell types [1]. In peripheral cells the sensor is activated during hypoxia and lack of energy substrates, switching on catabolic processes producing ATP and switching off anabolic processes consuming ATP [2,3]. The significance of AMPK in the periphery is widely acknowledged, but the role of this sensor in brain energy metabolism has been investigated mostly in neurons. Astrocytes play an important role in sustaining brain glutamate homeostasis and energy metabolism [4] and how AMPK regulates this in healthy astrocytes is largely unknown [5]. Type 2 diabetes mellitus (T2DM) has reached the level of a pandemic. Lately, convincing data has revealed that cognitive deficits are a common complication among T2DM patients [6, 7]. T2DM patients have a 1.5-2.5 times increased risk of dementia and one in 10-15 cases of dementia can be attributed to T2DM [8]. Furthermore, an Alzheimer’s disease (AD) like pattern of glucose hypometabolism is seen already in a pre-diabetic state [7]. Reduced AMPK activation may cause a decrease in catabolic processes, i.e. by glucose hypometabolism, thus, it is pertinent to investigate if dysfunctional AMPK signaling is involved in the observed cerebral glucose hypometabolism.

References

1. Winder, W.W. and D.G. Hardie, AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am J Physiol, 1999. 277(1 Pt 1): p. E1-10.

2. Hardie, D.G., AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev, 2011. 25(18): p. 1895-908.

3. Canto, C., et al., AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature, 2009. 458(7241): p. 1056-60.

4. McKenna, M.C., Glutamate pays its own way in astrocytes. Front Endocrinol (Lausanne), 2013. 4: p. 191.

5. Voss, C.M., et al., AMPK Activation Affects Glutamate Metabolism in Astrocytes. Neurochem Res, 2015.

6. Strachan, M.W., et al., Cognitive function, dementia and type 2 diabetes mellitus in the elderly. Nat Rev Endocrinol, 2011. 7(2): p. 108-14.

7. Baker, L.D., et al., Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes. Arch Neurol, 2011. 68(1): p. 51-7.

8. Exalto, L.G., et al., An update on type 2 diabetes, vascular dementia and Alzheimer's disease. Exp Gerontol, 2012. 47(11): p. 858-64.

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