Neuroepigenetics of Neurotrophin Signaling: Neurobiology of Anxiety and Affective Disorders.

This review examines the epigenetic of neurotrophin signaling in anxiety, affective disorders and related symptoms associated with drug addiction, in particular alcoholism. It is first important to understand the epigenetics of aversion memories, as they are so central to anxiety and affective disorders symptomology. The crucial role of neurotrophins in memory formation, in particular the brain-derived nerve growth factor (BDNF), is explored at the physiological and behavioral levels. Numerous studies describe how various epigenetic phenomena, mainly histone acetylation, histone methylation, DNA methylation, but also other less known epigenetic phenomena such as histone poly[ADP]-ribosylation and 5-HT2C receptor pre-mRNA editing, exert significant regulatory roles in aversion memory and fear extinction memory formation. Other models of anxiety and affective disorders, that use stress or transgenic constructs directed at elements of the stress axis or the serotonergic system, are then explored in relation with the epigenetic of neurotrophin signaling. Epigenetic marks differentially change according to brain areas. In the hippocampus for example, anxious or chronically stressed animals tend to show epigenetic changes that are at the opposite of those observed after memory consolidation following a brief aversive stimulus. Behaviorally relevant epigenetic changes have been found to be reversible by drug treatments. Surprisingly, moderate alcohol consumption may trigger, on the long term, changes of BDNF expression and of its epigenetic elements that are somehow similar to those produced by antidepressant drugs. However, alcohol withdrawal associated with anxiety symptoms has not yet been very well explored. Overall, it appears that a multidisciplinary view on the epigenetics of neurotrophin secretion might bring innovative treatments to psychiatric diseases involving stress and fear memories.