New Therapeutic Targets for Mood Disorders

Abstract

Existing pharmacological treatments for bipolar disorder (BPD) and major depressive disorder (MDD) are often insufficient for many patients. Here we describe a number of targets/compounds that clinical and preclinical studies suggest could result in putative novel treatments for mood disorders. These include: (1) glycogen synthase kinase-3 (GSK-3) and protein kinase C (PKC), (2) the purinergic system, (3) histone deacetylases (HDACs), (4) the melatonergic system, (5) the tachykinin neuropeptides system, (6) the glutamatergic system, and (7) oxidative stress and bioenergetics. The paper reviews data on new compounds that have shown antimanic or antidepressant effects in subjects with mood disorders, or similar effects in preclinical animal models. Overall, an improved understanding of the neurobiological underpinnings of mood disorders is critical in order to develop targeted treatments that are more effective, act more rapidly, and are better tolerated than currently available therapies.

7-Chlorokynurenic acid (7-CTKA) produces rapid antidepressant-like effects: through regulating hippocampal microRNA expressions involved in TrkB-ERK/Akt signaling pathways in mice exposed to chronic unpredictable mild stress

“…An analysis of predicted mRNA targets suggested that miR-34a regulate VEGFA, a growth factor implicated in depression in both humans and animal model (Dwivedi 2011). In addition, an important study revealed that miR-34a (down-regulation) and miR-144 (upregulation) could target the ERK-MAPK signaling pathway that had been known to involve in depressed and bipolar disorder (Zhou et al 2009;Machado-Vieira et al 2010), which paralleled to our present study. Mature miRNAs (miR-200a, miR-200b, and miR-200c) were predominantly associated with soluble components of the synaptic fractions (Lugli et al 2008).…”

Effects of angiotensin II receptor antagonists on anxiety and some oxidative stress markers in rat

“…A causal link between these two was also very recently demonstrated by several authors [50][51][52][53][54]. Moreover, different cell types studied in anxious mice showed a strong accumulation of intracellular ROS, in comparison to non-anxious mice, suggesting that oxidative stress is present in various cortex areas, as well as in hippocampus and cerebellum [55,56].…”

Circulating microRNA-144-5p is associated with depressive disorders

“…Signaling pathways targeted by miR-144 include the protein kinase C (PKC), Wnt/β-catenin, and PTEN pathways [45]. Some of them have been shown to be involved in the development of depression [49,50]. In addition, miR-144 was reported to be selectively upregulated in the aging brain of humans and was suggested to have neuroprotective functions.…”