Jana Haase
University of Dublin, Ireland
Jana Haase obtained her PhD from the Max-Planck-Institute for Molecular Genetics and the Free University Berlin. Following a period of postdoctoral research at Trinity College Dublin, she took up her current position at University College Dublin in 2003. The main theme in her research group is the regulation of neurotransmitter systems under physiological and pathological conditions, with a particular focus on the serotonergic system and its relevance to mood disorders as well as the mechanism of action of antidepressant drugs and psychostimulants. Over the past few years the group has been studying various aspects of serotonin transporter (SERT) regulation, including protein-lipid and protein-protein interactions. More recently, the main focus of her research has been the regulation of SERT in response to immune system activation, using both in vitro and in vivo approaches, including animal models relevant to human disease.
Molecular mechanisms of inflammation-induced depression – is anything “SERTain"?
The serotonin transporter (SERT) facilitates high affinity reuptake of the neurotransmitter serotonin from the extracellular fluid and dysregulation of transporter function has been implicated in a range of mood disorders including depression. Over the past few years, a number of studies have linked immune system activation to depression as well as to altered serotonin transporter activity. Advancing previous studies which focussed on acute effects of immune system activation, we used collagen-induced arthritis (CIA) in mice as a model of chronic inflammatory disease, to investigate the effect of prolonged inflammation on brain SERT function and behaviour. We found that CIA mice display anhedonia, a core depression-like behaviour. Moreover, behavioural symptoms are temporally correlated with a region-specific upregulation of SERT activity in the hippocampus which occurs at a post-translational level and is independent of SERT trafficking. Further analysis shows that tumour necrosis factor (TNF) αand its receptor (TNFR1) were specifically upregulated in the hippocampus of CIA mice, indicating altered TNFα signalling in this brain region. Anti-TNFα treatment using etanercept not only diminished joint inflammation, but also prevented the development of depression-like behaviour and the upregulation of SERT activity in the hippocampus, suggesting a key role for TNFα signalling in brain function regulation in this disease model. Current investigations in our lab are focused on understanding molecular determinants of sex differences in behavioural and neurochemical phenotypes in CIA mice. In summary, our study provides novel insight into molecular mechanisms underlying comorbid depression in chronic inflammatory diseases.