STAT3 identified as important factor in emotional reactivity

Date:
October 14, 2020
Source:
Medical University of Vienna
Summary:
Researchers showed that STAT3 plays an important role in the
serotonergic system as a molecular mediator for controlling
emotional reactivity, thereby establishing a mechanistic link
between the immune system, serotonergic transmission and affective
disorders such as depression.



FULL STORY ========================================================================== Numerous scientific studies indicate that inflammatory processes play a
key role in the development of psychiatric disorders. One of the areas
of particular interest is the interleukin 6/STAT3 signal transduction
pathway, which is associated with depression, schizophrenia, and bipolar disorder. In a study published in leading journal Molecular Psychiatry,
MedUni Vienna researchers led by Daniela Pollak from the Division
of Neurophysiology and Neuropharmacology showed that STAT3 plays an
important role in the serotonergic system as a molecular mediator for controlling emotional reactivity, thereby establishing a mechanistic
link between the immune system, serotonergic transmission and affective disorders such as depression.


==========================================================================
The STAT3 signal transduction pathway is activated in response to a
series of immunogenic and non-immunogenic stimuli, i.e. those that can and those that cannot trigger an immune response. "It was found that STAT3 is involved in nervous system functions that are important for controlling behaviour in physiological and pathological situations. In an earlier
study, we had managed to show that STAT3 also regulates the expression
of the serotonin transporter gene (Note: SERT)," explains Pollak.

Changes in serotonergic transmission, that is to say the transmission
of information from one neuron to another using serotonin as a messenger substance, correlate closely with pathological changes in depression or
other affective disorders. However, the interaction between the STAT3
signal transduction pathway and the neuronal information flow in the
brain and its importance in regulating emotional behaviour has not yet
been explored.

STAT3 deficiency reduces emotional reactivity The published work
therefore specifically investigated the significance of the STAT3 signal transduction pathway in the serotonergic system of the midbrain - -
an emotional regulation centre -- by targeted inhibition of STAT3 in a
mouse model. Says Pollak: "Where STAT3 was selectively absent from the serotonergic system of the midbrain, the mice displayed reduced, negative emotional reactivity in their behaviour and a diminished response to
the effects of amphetamine in the brain. These effects could be detected
in mice with reduced STAT3 expression both in a genetic and in a viral
model, so that it was possible to rule out developmental changes and to
show that an acute manipulation of STAT3 in the adult organism impacts
on emotional behaviour." In animals lacking in STAT3, there was also
found to be a change in the neuronal activity of serotonergic cells
of the midbrain. Changes in molecular networks that are significant
in neuropsychiatric illnesses were also found on the level of gene
expression. "The results of our study indicate that STAT3 plays an
important role as a molecular mediator in the serotonergic system for controlling emotional reactivity, thereby establishing a mechanistic
link between the immune system, serotonergic transmission and affective disorders."

========================================================================== Story Source: Materials provided by Medical_University_of_Vienna. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Sonali N. Reisinger, Spyros Sideromenos, Orsolya Horvath, Sophia
Derdak,
Ana Cicvaric, Francisco J. Monje, Martin Bilban, Martin Ha"ring,
Micaela Glat, Daniela D. Pollak. STAT3 in the dorsal raphe gates
behavioural reactivity and regulates gene networks associated
with psychopathology.

Molecular Psychiatry, 2020; DOI: 10.1038/s41380-020-00904-2 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201014114218.htm

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