Date Published: July 10, 2017
Publisher: Public Library of Science
Author(s): Huiying Wu, Christopher Cottingham, Liping Chen, Hongxia Wang, Pulin Che, Kexiang Liu, Qin Wang, Guangyu Wu.
Affective disorders impact nearly 10% of the adult population in the United States in a given year. Synaptic dysfunction has recently emerged as a key neurobiological mechanism underlying affective disorders such as anxiety and depression. In this study, we investigate the potential role of two synaptic scaffolding proteins, neurabin and spinophilin, in regulating anxiety- and depression-related behaviors at different ages using genetically deficient mice. Loss of the neurabin gene reduces anxiety-like behavior in the elevated zero maze in young adult mice (3–5 months old), but not in middle aged mice (11–13 months old), whereas loss of spinophilin decreases anxiety in middle-aged mice, but not in young adult mice. Neurabin knockout (KO) mice also show reduced immobility in the repeated force swim test (FST) at 3–5 months, but not 11–3 months, of age, compared to age- and strain-matched wild type (WT) controls. Conversely, spinophilin KO mice display a lower level of this behavioral despair than matched WT controls after repeated FST trials at the middle age (11–13 months) but not the young age (3–5 months). Together, these data indicate that, despite their structural similarities and overlapping function in regulating synaptic cytoskeleton, the two homologs neurabin and spinophilin play important yet distinct roles in the regulation of anxiety- and depression-like behaviors in an age-dependent manner. Our studies provide new insights into the complex neurobiology of affective disorders.
Affective disorders, such as anxiety and depression, are a major public health challenge carrying substantial social and economic burdens, impacting nearly 10% of the adult population in the United States in a given year . Despite extensive efforts in recent decades, we continue to lack a coherent view of the neurobiology of affective disorders, which limits the development of efficacious therapeutics. However, disruption of synaptic function, including both connectivity and plasticity, has recently emerged as a key neurobiological mechanism underlying affective disorders [2–4]. Dysregulation of synaptic proteins often occurs in these conditions, and may contribute to affective disorder etiology.