The Centre of New Technologies invites to a webinar by
Univ. Prof. Dr. Daniela Pollak,
Professor for Behavioral Biology, Department for Neurophysiolgy and –pharmacology,
Center for Physiology and Pharmacology, Medical University of Vienna, Austria
Title: STAT3 in the serotonergic system modulates emotional
reactivity relevant to mood and psychotic disorders
Date: 12th February 2021 (Friday)
Time: 12:00 pm (Central European Time)
Host: Prof. Marta B. Wiśniewska
Mental illness represents a growing disease burden globally, yet many patients do not seek treatment or do not respond to current treatment options. Finding new strategies to improve the quality of life of those affected remains challenging as our understanding of the pathophysiological processes is still limited.
Recently, the idea has emerged that studying common symptom complexes rather than distinct disease entities may be useful to disentangle underlying neurobiological mechanisms. For instance, increasing evidence suggests that mood disorders such as major depressive disorder (MDD) and bipolar disorder (BP), and psychotic disorders such as schizophrenia (SCZ), all of which are characterised to some degree by affective symptoms, may arise as the result of partially overlapping pathophysiological mechanisms.
Signal transducer and activator of transcription 3 (STAT3) is a ubiquitously expressed transcription factor, activated by a range of immunogenic and non- immunogenic stimuli. In addition to notable roles in cancer and a number of
processes relevant to neural function, in rodents STAT3 activity has been linked to behaviours pertinent to mood regulation by several lines of evidence. Here, we investigated whether STAT3 signalling within the serotonergic system, which is deeply involved in the control of affective behaviours, may regulate neurobiological processes contributing to altered phenotypes in behavioural paradigms relevant to mood and psychotic disorders.
Using conditional gene knockout and viral-mediated approaches in mice, we targeted STAT3 expression in the midbrain dorsal raphe (DR), containing the majority of cell bodies of serotonergic neurons in the brain. Mice constitutively lacking STAT3 in serotonergic cells (STAT3 KO) were less reactive in their behavioural responses in
paradigms relevant to stress coping and showed a diminished locomotor sensitisation response to d-amphetamine compared to controls, while serotonergic firing activity in the DR was increased in STAT3 KO. Analysis of transcriptional changes in the DR of STAT3 KO revealed a disproportionate presence of genes linked to biological processes highly relevant to neuropsychiatric disorders. Subsequent viral-mediated knockdown of STAT3 in adult mice produced the same behavioural effects as the germline genetic knockout strategy, suggesting that short-term disruption of STAT3 activity in the DR was sufficient to induce the observed behavioural changes.
Taken together, we suggest that DR STAT3, via the transcriptional control of genes and gene networks pertinent to cell excitability and synaptic function, may constitute a molecular link between upstream modulators of STAT3 activity, serotonergic neurotransmission and the control of behaviours relevant to psychopathology.