The molecular associations of depression behavior with anxiety and memory deficit suggested a potential approach to improve therapeutic intervention through P11 in these disorders.
Reviewing the literature concerning BNDF, p11 and Homer1a we here describe a molecular network in which these molecules interact with each other finally leading to facilitation of AMPA receptor signaling and plasticity, corroborating the current idea of AMPA receptors being a promising drug target in depression.
These results have identified p11 in LHb as a key molecular determinant regulating negative emotions, which may help to understand the molecular and cellular basis of depression.
Our results have identified p11 as a key molecule in a specific cell type that regulates stress-induced depression, which provides a framework for the development of new strategies to treat stress-associated mental illnesses.
Monocyte, natural killer (NK) cell, and cytotoxic T-cell p11 levels were positively associated with the severity of PD, and NK cell p11 levels were positively associated with depression scores.
Our findings suggested that p11 might be a potential regulator on 5-HTR1b and 5-HTR4 as well as a predictor of or a therapeutic target for IFN-α-induced depression.
In this study, we tested the leukocyte mRNA expression levels of genes belonging to glucocorticoid receptor (GR) function (FKBP-4, FKBP-5, and GR), inflammation (interleukin (IL)-1α, IL-1β, IL-4, IL-6, IL-7, IL-8, IL-10, macrophage inhibiting factor (MIF), and tumor necrosis factor (TNF)-α), and neuroplasticity (brain-derived neurotrophic factor (BDNF), p11 and VGF), in healthy controls (n=34) and depressed patients (n=74), before and after 8 weeks of treatment with escitalopram or nortriptyline, as part of the Genome-based Therapeutic Drugs for Depression study.
In conclusion, our data further support a role for P11 in depression-like states and suggest that this gene is controlled by epigenetic mechanisms that can be affected by antidepressant treatment.
Understanding the chromatin remodeling involved in the glucocorticoid-mediated increase of p11 expression by stress may clarify stress-induced over-expression of p11 and also identify a new therapeutic target for post-traumatic disorder and depressive disorders, i.e., chromatin remodeling.
Understanding the chromatin remodeling involved in the glucocorticoid-mediated increase of p11 expression by stress may clarify stress-induced over-expression of p11 and also identify a new therapeutic target for post-traumatic disorder and depressive disorders, i.e., chromatin remodeling.
Taken together, the data suggest that gene therapies aimed at enhancing p11 in the NAcc may represent promising new approaches for treating depression; however, a large number of clinical and regulatory issues must be overcome before such therapies can be implemented.
A review of the literature provides strong evidence that 5-HT(1B) receptors and related factors such as p11 are involved in the pathophysiology of depression.
Recently, a study demonstrated that dexamethasone (Dex), a synthetic glucocorticoid, can up-regulate p11, known as S100A10-protein which is down-regulated in patients with depression, (Yao et al., 1999; Huang et al., 2003) a common comorbid disorder in PTSD.
Furthermore, brain p11 mRNA expression is lower in post mortem brains from patients who were suffering from depression and had committed suicide compared with control subjects who had died from other causes.
Recent evidence suggests a potential role for the p11 gene in conferring risk to depressive disorders. p11 has been shown to influence serotonergic transmission, and its expression was found to be reduced in a mouse model of depression, as well as in post-mortem brain tissue from major depressive disorder (MDD) cases.
We have found that the serotonin 1B receptor [5-hydroxytryptamine (5-HT1B) receptor] interacts with p11. p11 increases localization of 5-HT1B receptors at the cell surface. p11 is increased in rodent brains by antidepressants or electroconvulsive therapy, but decreased in an animal model of depression and in brain tissue from depressed patients.