TY  - JOUR
A1  - Gutknecht, Lise
A1  - Popp, Sandy
A1  - Waider, Jonas
A1  - Sommerlandt, Frank M. J.
A1  - Göppner, Corinna
A1  - Post, Antonia
A1  - Reif, Andreas
A1  - van den Hove, Daniel
A1  - Strekalova, Tatyana
A1  - Schmitt, Angelika
A1  - Colaςo, Maria B. N.
A1  - Sommer, Claudia
A1  - Palme, Rupert
A1  - Lesch, Klaus-Peter
T1  - Interaction of brain 5-HT synthesis deficiency, chronic stress and sex differentially impact emotional behavior in Tph2 knockout mice
JF  - Psychopharmacology
N2  - Rationale
While brain serotonin (5-HT) function is implicated in gene-by-environment interaction (GxE) impacting the vulnerability-resilience continuum in neuropsychiatric disorders, it remains elusive how the interplay of altered 5-HT synthesis and environmental stressors is linked to failure in emotion regulation.

Objective
Here, we investigated the effect of constitutively impaired 5-HT synthesis on behavioral and neuroendocrine responses to unpredictable chronic mild stress (CMS) using a mouse model of brain 5-HT deficiency resulting from targeted inactivation of the tryptophan hydroxylase-2 (Tph2) gene.

Results
Locomotor activity and anxiety- and depression-like behavior as well as conditioned fear responses were differentially affected by Tph2 genotype, sex, and CMS. Tph2 null mutants (Tph2\(^{−/−}\)) displayed increased general metabolism, marginally reduced anxiety- and depression-like behavior but strikingly increased conditioned fear responses. Behavioral modifications were associated with sex-specific hypothalamic-pituitary-adrenocortical (HPA) system alterations as indicated by plasma corticosterone and fecal corticosterone metabolite concentrations. Tph2\(^{−/−}\) males displayed increased impulsivity and high aggressiveness. Tph2\(^{−/−}\) females displayed greater emotional reactivity to aversive conditions as reflected by changes in behaviors at baseline including increased freezing and decreased locomotion in novel environments. However, both Tph2\(^{−/−}\) male and female mice were resilient to CMS-induced hyperlocomotion, while CMS intensified conditioned fear responses in a GxE-dependent manner.

Conclusions
Our results indicate that 5-HT mediates behavioral responses to environmental adversity by facilitating the encoding of stress effects leading to increased vulnerability for negative emotionality.
KW  - Serotonin
KW  - Tryptophan hydroxylase-2 (Tph2)
KW  - chronic stress
KW  - gene-by-environment interaction
KW  - anxiety
KW  - fear
KW  - depression
KW  - aggression
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154586
VL  - 232
SP  - 2429
EP  - 2441
ER  - 
TY  - JOUR
A1  - Kittel-Schneider, Sarah
A1  - Kenis, Gunter
A1  - Schek, Julia
A1  - van den Hove, Daniel
A1  - Prickaerts, Jos
A1  - Lesch, Klaus-Peter
A1  - Steinbusch, Harry
A1  - Reif, Andreas
T1  - Expression of monoamine transporters, nitric oxide synthase 3, and neurotrophin genes in antidepressant-stimulated astrocytes
JF  - Frontiers in Psychiatry
N2  - Background: There is increasing evidence that glial cells play a role in the pathomechanisms of mood disorders and the mode of action of antidepressant drugs. 
Methods: To examine whether there is a direct effect on the expression of different genes encoding proteins that have been implicated in the pathophysiology of affective disorders, primary astrocyte cell cultures from rats were treated with two different antidepressant drugs, imipramine and escitalopram, and the RNA expression of brain-derived neurotrophic factor (Bdnf), serotonin transporter (5Htt), dopamine transporter (Dat), and endothelial nitric oxide synthase (Nos3) was examined. 
Results: Stimulation of astroglial cell culture with imipramine, a tricyclic antidepressant, led to a significant increase of the Bdnf RNA level whereas treatment with escitalopram did not. In contrast, 5Htt was not differentially expressed after antidepressant treatment. Finally, neither Dat nor Nos3 RNA expression was detected in cultured astrocytes. 
Conclusion: These data provide further evidence for a role of astroglial cells in the molecular mechanisms of action of antidepressants.
KW  - monoamine transporters
KW  - BDNF
KW  - geneexpression
KW  - astrocytes
KW  - glia
KW  - depression
KW  - antidepressant
KW  - mechanismofaction
KW  - nitricoxidesynthase
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123627
VL  - 3
ER  -