MicroRNAs in Mental Health: From Biological Underpinnings to Potential Therapies

Abstract

Psychiatric illnesses are disabling disorders with poorly understood underlying pathophysiologies. However, it is becoming increasingly evident that these illnesses result from disruptions across whole cellular networks rather than any particular monoamine system. Recent evidence continues to support the hypothesis that these illnesses arise from impairments in cellular plasticity cascades, which lead to aberrant information processing in the circuits that regulate mood, cognition, and neurovegetative functions (sleep, appetite, energy, etc). As a result, many have begun to consider future therapies that would be capable of affecting global changes in cellular plasticity to restore appropriate synaptic function and neuronal connectivity. MicroRNAs (miRNAs) are non-coding RNAs that can repress the gene translation of hundreds of their targets and are therefore well-positioned to target a multitude of cellular mechanisms. Here, we review some properties of microRNAs and show they are altered by stress, glucocorticoids, mood stabilizers, and in a particular psychiatric disorder, schizophrenia. While this field is still in its infancy, we consider their potential for regulating behavioral phenotypes and targeting key predicted signaling cascades that are implicated in psychiatric illness. Clearly, considerable research is required to better determine any therapeutic potential of targeting microRNAs; however, these agents may provide the next generation of effective therapies for psychiatric illnesses.

MicroRNA-326 acts as a molecular switch in the regulation of midbrain urocortin 1 expression

“…38,[40][41][42] For example, early life stress results in increased expression of a variety of miRNAs in the prefrontal cortex. 43 Moreover, miRNA-183 and miR-134 levels are upregulated in the amygdala under acute stress.…”

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

“…These in primary health care common psychiatric disorders are associated with poor quality of life and reduced life expectancy, placing a large economic burden on society. Several studies have explored the underlying pathophysiological and etiological mechanisms [6][7][8]. Current evidence suggests that the onset and progression of depression appear to be influenced by multiple factors, including neurotransmitter systems [9,10], stress [7,11], and genetic susceptibility [7,12].…”

Identification and quantitative analyses of microRNAs located in the distal axons of sympathetic neurons

“…The functions of individual miRNAs in neurons are just beginning to emerge, and multiple lines of evidence point to the widespread involvement of miRNAs in various neurological diseases (for review, see Bassell and Warren 2008;Hunsberger et al 2009). In addition, recent studies have elucidated several roles for neural miRNAs at various stages of synaptic development, including dendritogenesis, synapse formation, and synapse maturation.…”