In the study, "Serotonin effects on human iPSC-derived neural cell functions: from mitochondria to depression", Cardon et al examines the effects of serotonin on brain cells derived from individuals with Major Depressive Disorder (MDD) and mitochondrial disorders. The study uses induced pluripotent stem cells (iPSCs) to explore how chronic serotonin treatment impacts gene expression, mitochondrial function, calcium homeostasis, and neuronal excitability in these cells.
Key Facts:
Gene Expression and Mitochondrial Function: Serotonin influenced gene expression related to mitochondrial function, suggesting a potential impact on cellular energy dynamics.
Calcium Homeostasis and Neuronal Excitability: In astrocytes, serotonin normalized calcium levels and mitochondrial membrane potential. Whereas in neurons, serotonin treatments led to changes in resting membrane potential, ion currents, action potentials, and postsynaptic currents, generally enhancing cellular excitability and reducing calcium levels- which might help protect against excessive nerve cell activity and potential damage.
Differential Responses Based on Patient Conditions: Neurons from the antidepressant-resistant patient showed increased excitability in response to serotonin, indicating potential pathways for overcoming treatment resistance at the cellular level. However, in the patient with a mitochondrial disorder, serotonin also increased excitability but raised concerns due to the potential exacerbation of underlying hyperexcitability common in mitochondrial pathologies.
Implications:
Treatment Considerations: The findings underscore the necessity of personalised approaches in treating depression, especially considering the underlying biological differences among individuals. Caution is needed when prescribing SSRIs to patients with mitochondrial disorder due to risk of clinical deterioration and worsening of symptoms.
Serotonin's role: While traditionally viewed through the lens of the monoamine theory, serotonin's impact on mitochondrial dynamics and cellular excitability highlights a more complex role in neuropsychiatric disorders.
Future Research Directions: Further studies are needed to understand how these cellular changes translate into clinical effects and to explore potential pathways for targeting mitochondrial function in depression therapy.
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