scholarly journals Establishment of a Large Collection of Cells from Major Depressive Disorder Patients to Model Disease and Therapy Response in Vitro

2019 ◽  
Vol 3 (2) ◽  

Major Depressive Disorder (MDD) is a multifactorial psychiatric condition that affects 4.4% of the world population, causing substantial personal suffering, disability and social costs. Current pharmacological treatments for MDD do not effect remission in 30% of patients. The development of in vitro models for MDD will aid the understanding of this disorder, its pharmacogenomics, and the development of new therapies. Although hiPSCs from 6 MDD patients have been established, given the complexity and heterogeneity of the disease much larger sample sizes may be needed to fully model the disorder in vitro. To this end, we established a collection of 66 primary cells and 10 induced pluripotent stem cells (hiPSCs) from a sample of clinically well-characterized MMD patients, who were participants of a clinical study that compared the effect of transcranial direct current stimulation (tCDS) versus escitalopram on the treatment of MDD. Cells were differentiated in vitro into serotoninergic neurons, a clinically relevant cell type for MMD. This collection of cells increases significantly the number of available samples from MDD patients, and thus will contribute to research into the molecular basis of depression.

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1728
Author(s):  
Dinyadarshini Johnson ◽  
Sivakumar Thurairajasingam ◽  
Vengadesh Letchumanan ◽  
Kok-Gan Chan ◽  
Learn-Han Lee

The field of probiotic has been exponentially expanding over the recent decades with a more therapeutic-centered research. Probiotics mediated microbiota modulation within the microbiota–gut–brain axis (MGBA) have been proven to be beneficial in various health domains through pre-clinical and clinical studies. In the context of mental health, although probiotic research is still in its infancy stage, the promising role and potential of probiotics in various mental disorders demonstrated via in-vivo and in-vitro studies have laid a strong foundation for translating preclinical models to humans. The exploration of the therapeutic role and potential of probiotics in major depressive disorder (MDD) is an extremely noteworthy field of research. The possible etio-pathological mechanisms of depression involving inflammation, neurotransmitters, the hypothalamic–pituitary–adrenal (HPA) axis and epigenetic mechanisms potentially benefit from probiotic intervention. Probiotics, both as an adjunct to antidepressants or a stand-alone intervention, have a beneficial role and potential in mitigating anti-depressive effects, and confers some advantages compared to conventional treatments of depression using anti-depressants.


2017 ◽  
Vol 1 ◽  
pp. 247054701772045 ◽  
Author(s):  
Mounira Banasr ◽  
Ashley Lepack ◽  
Corey Fee ◽  
Vanja Duric ◽  
Jaime Maldonado-Aviles ◽  
...  

Background Evidence continues to build suggesting that the GABAergic neurotransmitter system is altered in brains of patients with major depressive disorder. However, there is little information available related to the extent of these changes or the potential mechanisms associated with these alterations. As stress is a well-established precipitant to depressive episodes, we sought to explore the impact of chronic stress on GABAergic interneurons. Methods Using western blot analyses and quantitative real-time polymerase chain reaction, we assessed the effects of five-weeks of chronic unpredictable stress exposure on the expression of GABA-synthesizing enzymes (GAD65 and GAD67), calcium-binding proteins (calbindin, parvalbumin, and calretinin), and neuropeptides co-expressed in GABAergic neurons (somatostatin, neuropeptide Y, vasoactive intestinal peptide, and cholecystokinin) in the prefrontal cortex and hippocampus of rats. We also investigated the effects of corticosterone and dexamethasone exposure on these markers in vitro in primary cortical and hippocampal cultures. Results We found that chronic unpredictable stress induced significant reductions of GAD67 protein levels in both the prefrontal cortex and hippocampus of chronic unpredictable stress-exposed rats but did not detect changes in GAD65 protein expression. Similar protein expression changes were found in vitro in cortical neurons. In addition, our results provide clear evidence of reduced markers of interneuron population(s), namely somatostatin and neuropeptide Y, in the prefrontal cortex, suggesting these cell types may be selectively vulnerable to chronic stress. Conclusion Together, this work highlights that chronic stress induces regional and cell type-selective effects on GABAergic interneurons in rats. These findings provide additional supporting evidence that stress-induced GABA neuron dysfunction and cell vulnerability play critical roles in the pathophysiology of stress-related illnesses, including major depressive disorder.


2020 ◽  
Vol 81 (5) ◽  
pp. 593-599 ◽  
Author(s):  
Elisabetta Maffioletti ◽  
Massimo Gennarelli ◽  
Chiara Magri ◽  
Luisella Bocchio‐Chiavetto ◽  
Marco Bortolomasi ◽  
...  

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jessica Daniela Schroder ◽  
Julia Beatrice de Araújo ◽  
Tacio de Oliveira ◽  
Airam Barbosa de Moura ◽  
Gabriel Rodrigo Fries ◽  
...  

Abstract Major depressive disorder (MDD) is one of the most prevalent and debilitating psychiatric disorders, with a large number of patients not showing an effective therapeutic response to available treatments. Several biopsychosocial factors, such as stress in childhood and throughout life, and factors related to biological aging, may increase the susceptibility to MDD development. Included in critical biological processes related to aging and underlying biological mechanisms associated with MDD is the shortening of telomeres and changes in telomerase activity. This comprehensive review discusses studies that assessed the length of telomeres or telomerase activity and function in peripheral blood cells and brain tissues of MDD individuals. Also, results from in vitro protocols and animal models of stress and depressive-like behaviors were included. We also expand our discussion to include the role of telomere biology as it relates to other relevant biological mechanisms, such as the hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, inflammation, genetics, and epigenetic changes. In the text and the discussion, conflicting results in the literature were observed, especially considering the size of telomeres in the central nervous system, on which there are different protocols with divergent results in the literature. Finally, the context of this review is considering cell signaling, transcription factors, and neurotransmission, which are involved in MDD and can be underlying to senescence, telomere shortening, and telomerase functions.


Sign in / Sign up

Export Citation Format

Share Document