scholarly journals Benefits of Hormone Therapy Estrogens Depend on Estrogen Type: 17β-Estradiol and Conjugated Equine Estrogens Have Differential Effects on Cognitive, Anxiety-Like, and Depressive-Like Behaviors and Increase Tryptophan Hydroxylase-2 mRNA Levels in Dorsal Raphe Nucleus Subregions

2016 ◽  
Vol 10 ◽  
Author(s):  
Ryoko Hiroi ◽  
Giulia Weyrich ◽  
Stephanie V. Koebele ◽  
Sarah E. Mennenga ◽  
Joshua S. Talboom ◽  
...  
2011 ◽  
Vol 19 (9) ◽  
pp. 792-802 ◽  
Author(s):  
Tonita E. Wroolie ◽  
Heather A. Kenna ◽  
Katherine E. Williams ◽  
Bevin N. Powers ◽  
Megan Holcomb ◽  
...  

2020 ◽  
Vol 21 (22) ◽  
pp. 8784
Author(s):  
Elena M. Kondaurova ◽  
Alexander Ya. Rodnyy ◽  
Tatiana V. Ilchibaeva ◽  
Anton S. Tsybko ◽  
Dmitry V. Eremin ◽  
...  

The influence of genetic background on sensitivity to drugs represents a topical problem of personalized medicine. Here, we investigated the effect of chronic (20 mg/kg, 14 days, i.p.) antidepressant fluoxetine treatment on recombinant B6-M76C mice, differed from control B6-M76B mice by CBA-derived 102.73–110.56 Mbp fragment of chromosome 13 and characterized by altered sensitivity of 5-HT1A receptors to chronic 8-OH-DPAT administration and higher 5-HT1A receptor mRNA levels in the frontal cortex and hippocampus. Significant changes in the effects of fluoxetine treatment on behavior and brain 5-HT system in recombinant B6-M76C mice were revealed. In contrast to B6-M76B mice, in B6-M76C mice, fluoxetine produced pro-depressive effects, assessed in a forced swim test. Fluoxetine decreased 5-HT1A receptor mRNA levels in the cortex and hippocampus, reduced 5-HT1A receptor protein levels and increased receptor silencer Freud-1 protein levels in the hippocampus of B6-M76C mice. Fluoxetine increased mRNA levels of the gene encoding key enzyme for 5-HT synthesis in the brain, tryptophan hydroxylase-2, but decreased tryptophan hydroxylase-2 protein levels in the midbrain of B6-M76B mice. These changes were accompanied by increased expression of the 5-HT transporter gene. Fluoxetine reduced 5-HT and 5-HIAA levels in cortex, hippocampus and midbrain of B6-M76B and in cortex and midbrain of B6-M76C; mice. These data demonstrate that changes in genetic background may have a dramatic effect on sensitivity to classic antidepressants from the Selective Serotonin Reuptake Inhibitors family. Additionally, the results provide new evidence confirming our idea on the disrupted functioning of 5-HT1A autoreceptors in the brains of B6-M76C mice, suggesting these mice as a model of antidepressant resistance.


Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 3952-3959 ◽  
Author(s):  
Christiane Otto ◽  
Iris Fuchs ◽  
Helga Altmann ◽  
Mario Klewer ◽  
Alexander Walter ◽  
...  

The role of progestins in combined hormone therapy is the inhibition of uterine epithelial cell proliferation. The Women’s Health Initiative study provided evidence for an increased risk of breast cancer in women treated with conjugated equine estrogens plus the synthetic progestin medroxyprogesterone acetate (MPA), compared with conjugated equine estrogens-only treatment. These findings continue to be discussed, and it remains to be clarified whether the results obtained for MPA in the Women’s Health Initiative study are directly applicable to other progestins used in hormone therapy. In this study we compared in a mouse model the effects of the synthetic progestins, MPA, and drospirenone in two major target organs: the uterus and mammary gland. As quantitative measures of progestin activity, we analyzed maintenance of pregnancy, ductal side branching in the mammary gland, and proliferation of mammary and uterine epithelial cells as well as target gene induction in both organs. The outcome of this study is that not all synthetic progestins exhibit the same effects. MPA demonstrated uterine activity and mitogenic activity in the mammary gland at the same doses. In contrast, drospirenone behaved similarly to the natural hormone, progesterone, and exhibited uterine activity at doses lower than those leading to considerable proliferative effects in the mammary gland. We hypothesize that the safety of combined hormone therapy in postmenopausal women may be associated with a dissociation between the uterine and mammary gland activities of the progestin component.


2021 ◽  
pp. 1-18
Author(s):  
Christian Ulrich von Linstow ◽  
Jonas Waider ◽  
Marianne Skov-Skov Bergh ◽  
Marco Anzalone ◽  
Cecilie Madsen ◽  
...  

Background: A decline of brain serotonin (5-HT) is held responsible for the changes in mood that can be observed in Alzheimer’s disease (AD). However, 5-HT’ergic signaling is also suggested to reduce the production of pathogenic amyloid-4β (Aβ). Objective: To investigate the effect of targeted inactivation of tryptophan hydroxylase-2 (Tph2), which is essential for neuronal 5-HT synthesis, on amyloidosis in amyloid precursor protein (APP)swe/presenilin 1 (PS1) ΔE9 transgenic mice. Methods: Triple-transgenic (3xTg) APP/PS1 mice with partial (+/-) or complete Tph2 knockout (–/–) were allowed to survive until 6 months old with APP/PS1, Tph2–/–, and wildtype mice. Survival and weight were recorded. Levels of Aβ 42/40/38, soluble APPα (sAβPPα) and sAβPPβ, and cytokines were analyzed by mesoscale, neurotransmitters by mass spectrometry, and gene expression by quantitative PCR. Tph2, microglia, and Aβ were visualized histologically. Results: Tph2 inactivation in APP/PS1 mice significantly reduced viability, without impacting soluble and insoluble Aβ 42 and Aβ 40 in neocortex and hippocampus, and with only mild changes of soluble Aβ 42/Aβ 40. However, sAβPPα and sAβPPβ in hippocampus and Aβ 38 and Aβ 40 in cerebrospinal fluid were reduced. 3xTg–/–mice were devoid of Tph2 immunopositive fibers and 5-HT. Cytokines were unaffected by genotype, as were neocortical TNF, HTR2a and HTR2b mRNA levels in Tph2–/– mice. Microglia clustered around Aβ plaques regardless of genotype. Conclusion: The results suggest that Tph2 inactivation influences AβPP processing, at least in the hippocampus, although levels of Aβ are unchanged. The reduced viability of 3xTg–/–mice could indicate that 5-HT protects against the seizures that can impact the viability of APP/PS1 mice.


2016 ◽  
Vol 20 (3) ◽  
pp. 451-462
Author(s):  
Helene Bach ◽  
Victoria Arango ◽  
Suham A. Kassir ◽  
Andrew J. Dwork ◽  
J. John Mann ◽  
...  

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