MicroRNAs, Stem Cells in Bipolar Disorder, and Lithium Therapeutic Approach

Coradduzza, Donatella; Garroni, Giuseppe; Congiargiu, Antonella; Balzano, Francesca; Cruciani, Sara; Sedda, Stefania; Nivoli, Alessandra; Maioli, Margherita

doi:10.3390/ijms231810489

Cited by 12 publications

(7 citation statements)

References 131 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We assume that the mechanisms behind this finding may be Li‐induced microRNA expression and epigenetic changes. Several microRNAs are known to be altered by Li treatment, among which mirR‐144 is widely expressed in the brain and is upregulated by Li, and its target is considered to be the PTEN pathway 42 . In addition, mood stabilizers, including Li, have been suggested to potentially alter the DNA methylation status 43 in many regions, which were also altered in the postmortem brains of patients with BD in this study, suggesting that Li may affect the expression of several genes involved in BD's pathology by altering their DNA methylation.…”

Section: Discussionmentioning

confidence: 99%

Marked alteration of phosphoinositide signaling‐associated molecules in postmortem prefrontal cortex with bipolar disorder

Hino,

Kunii,

Shishido

et al. 2024

Neuropsychopharm Rep

View full text Add to dashboard Cite

AimThe etiology of bipolar disorder (BD) remains unknown; however, lipid abnormalities in BD have received increasing attention in recent years. In this study, we examined the expression levels of enzyme proteins associated with the metabolic pathway of phosphoinositides (PIs) and their downstream effectors, protein kinase B (Akt1) and glycogen synthase kinase 3β (GSK3β), which have been assumed to be the targets of mood stabilizers such as lithium, in the postmortem brains of patients with BD.MethodsThe protein expression levels of phosphatidylinositol 4‐phosphate 5‐kinase type‐1 gamma (PIP5K1C), phosphatidylinositol 4‐kinase alpha (PIK4CA), phosphatase and tensin homolog deleted from chromosome 10 (PTEN), Akt1, and GSK3β were measured using enzyme‐linked immunosorbent assays and multiplex fluorescent bead‐based immunoassays in the prefrontal cortex (PFC). Specifically, PTEN, Akt1, GSK3β, and PIP5K1C were measured in seven BD patients and 48 controls. Additionally, PIK4CA was analyzed in 10 cases and 34 controls.ResultsPTEN expression levels were markedly decreased in the PFCs of patients with BD, whereas those of Akt and GSK3β were prominently elevated. Moreover, patients medicated with lithium exhibited higher Akt1 expression levels and lower PTEN expression levels in comparison with the untreated group.ConclusionOur results suggest that the expression levels of Akt1/GSK3β and its upstream regulator PTEN are considerably altered.

show abstract

Section: Discussionmentioning

confidence: 99%

Marked alteration of phosphoinositide signaling‐associated molecules in postmortem prefrontal cortex with bipolar disorder

Hino,

Kunii,

Shishido

et al. 2024

Neuropsychopharm Rep

View full text Add to dashboard Cite

show abstract

“…Furthermore, anxiety, depression risk, neuroticism, and serotonergic neurotransmission have all been linked to altered serum BDNF levels and BDNF gene polymorphism [ 2 ]. Lithium augmentation refers to the addition of lithium to an antidepressant in the acute treatment phase of depression [ 41 , 42 ]. Antidepressant augmentation with lithium is a well-studied augmentation therapy for patients with depression who have not been responding well to antidepressant therapy [ 41 ].…”

Section: Growth Factors Involved In Depressionmentioning

confidence: 99%

Plausible Role of Stem Cell Types for Treating and Understanding the Pathophysiology of Depression

Sachdeva¹,

Ghosh

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

Major Depressive Disorder (MDD), colloquially known as depression, is a debilitating condition affecting an estimated 3.8% of the population globally, of which 5.0% are adults and 5.7% are above the age of 60. MDD is differentiated from common mood changes and short-lived emotional responses due to subtle alterations in gray and white matter, including the frontal lobe, hippocampus, temporal lobe, thalamus, striatum, and amygdala. It can be detrimental to a person’s overall health if it occurs with moderate or severe intensity. It can render a person suffering terribly to perform inadequately in their personal, professional, and social lives. Depression, at its peak, can lead to suicidal thoughts and ideation. Antidepressants manage clinical depression and function by modulating the serotonin, norepinephrine, and dopamine neurotransmitter levels in the brain. Patients with MDD positively respond to antidepressants, but 10–30% do not recuperate or have a partial response accompanied by poor life quality, suicidal ideation, self-injurious behavior, and an increased relapse rate. Recent research shows that mesenchymal stem cells and iPSCs may be responsible for lowering depression by producing more neurons with increased cortical connections. This narrative review discusses the plausible functions of various stem cell types in treating and understanding depression pathophysiology.

show abstract

“…They have been associated with BD etiology in expression studies of postmortem brain tissue of BD patients (18). Furthermore, lithium and valproic acid (VPA), the primary mood stabilizers used in BD treatment, affect miRNA expression (19,20). Variants in miRNA genes associated with a higher risk of BD have been identified (21), and manipulation of one of these miRNAs (miR-499-5p) caused cognitive impairments and mood disorder-related endophenotypes in rats (14,22).…”

Section: Introductionmentioning

confidence: 99%

Early life stress-induced miR-708-5p affects bipolar disorder-associated phenotypes through neuronatin downregulation

Gilardi,

Martins,

Bianco

et al. 2024

Preprint

View full text Add to dashboard Cite

The underlying physiological and molecular mechanisms of bipolar disorder (BD) remain largely unknown. Here, by using unbiased small RNA sequencing in peripheral blood mononuclear cells (PBMCs), we found that miR-708-5p, a microRNA that was previously associated with BD, is the most strongly upregulated microRNA in peripheral blood of both healthy human subjects with a high genetic or environmental predisposition to develop mood disorders (MDs). Furthermore, miR-708-5p is strongly upregulated in patients diagnosed with BD and has potential in conjunction with the previously identified miR-499-5p to differentiate BD patients from patients suffering from major depressive disorder (MDD) and healthy controls. miR-708 is also upregulated in the hippocampus of wild type juvenile rats that underwent social isolation, as well as in juvenile rats heterozygous for the BD risk gene Cacna1c. Furthermore, ectopic overexpression of miR-708-5p in the hippocampus of adult male mice leads to BD-associated endophenotypes, such as reduced behavioral despair, enhanced compulsivity, and short-term memory impairments. miR-708-5p directly targets Neuronatin (Nnat), an endoplasmic reticulum (ER) resident protein involved in calcium homeostasis. Restoring Nnat expression in the hippocampus of miR-708-5p overexpressing mice rescues BD-associated endophenotypes. In summary, we functionally link miR-708-5p dependent regulation of Nnat to BD, with potential implications for BD diagnosis and therapy.

show abstract

MicroRNAs, Stem Cells in Bipolar Disorder, and Lithium Therapeutic Approach

Cited by 12 publications

References 131 publications

Marked alteration of phosphoinositide signaling‐associated molecules in postmortem prefrontal cortex with bipolar disorder

Marked alteration of phosphoinositide signaling‐associated molecules in postmortem prefrontal cortex with bipolar disorder

Plausible Role of Stem Cell Types for Treating and Understanding the Pathophysiology of Depression

Early life stress-induced miR-708-5p affects bipolar disorder-associated phenotypes through neuronatin downregulation

Contact Info

Product

Resources

About