Palladin Is a Neuron-Specific Translational Target of mTOR Signaling That Regulates Axon Morphogenesis.

The mTOR signaling pathway regulates protein synthesis and diverse aspects of neuronal morphology that are important for brain development and function. To identify proteins controlled translationally by mTOR signaling, we performed ribosome profiling analyses in mouse cortical neurons and embryonic stem cells upon acute mTOR inhibition. Among proteins whose translation was significantly affected by mTOR inhibition selectively in neurons, we identified the cytoskeletal regulator protein palladin, which is localized within the cell body and axons in hippocampal neurons. Knockdown of palladin eliminated supernumerary axons induced by suppression of the tuberous sclerosis complex protein TSC1 in neurons, demonstrating that palladin regulates neuronal morphogenesis downstream of mTOR signaling. Our findings provide novel insights into an mTOR-dependent mechanism that controls neuronal morphogenesis through translational regulation.SIGNIFICANCE STATEMENT This study reports the discovery of neuron-specific protein translational responses to alterations of mTOR activity. By using ribosome profiling analysis, which can reveal the location and quantity of translating ribosomes on mRNAs, multiple aspects of protein translation were quantitatively analyzed in mouse embryonic stem cells and cortical neurons upon acute mTOR inhibition. Neurons displayed distinct patterns of ribosome occupancy for each codon and ribosome stalling during translation at specific positions of mRNAs. Importantly, the cytoskeletal regulator palladin was identified as a translational target protein of mTOR signaling in neurons. Palladin operates downstream of mTOR to modulate axon morphogenesis. This study identifies a novel mechanism of neuronal morphogenesis regulated by mTOR signaling through control of translation of the key protein palladin.

[Optimistic bias in help-seeking intentions and behaviors for depressive symptoms].

The present study investigated the effect of optimistic bias on help-seeking intentions and behaviors in relation to health care professionals and nonprofessionals for depressive symptoms. In addition, the study tested the hypothesis that seeking help from professionals poses a greater threat for self-esteem than from non-professionals. A questionnaire survey (N = 462) using clinical vignettes was conducted with university students. The results suggested that optimistic bias had an impact on help-seeking intentions and behaviors directed towards both health care professionals and nonprofessionals. There seemed to be a relatively stronger threat to self-esteem in help-seeking involving nonprofessionals and a weaker threat in help-seeking involving professionals, contrary to previous studies. The results were explained by the threat to self-esteem and equity theories. Understanding the rationale of optimistic bias and symptom recognition in the help-seeking process may provide relevant information to bridge the service gap in the treatment of depression.

Psychometric properties of the Japanese CES-D, SDS, and PHQ-9 depression scales in university students.

We used an item response theory (IRT) model to simultaneously compare the psychometric properties of 3 commonly used self-report depression scales translated into Japanese-the Zung Self-Rating Depression Scale (SDS), the Center for Epidemiologic Studies Depression Scale (CES-D), and the Patient Health Questionnaire Depression Scale (PHQ-9)-in a Japanese university student sample. Although the 3 scales were likely to measure the same underlying construct-that is, depression-the choices of the negatively worded items in the SDS and CES-D did not function well. The CES-D provided more information than the other scales at the range of depression severity approximately from the mean through 2 standard deviations above the mean, while the PHQ-9 provided more information for the other degrees of depression. The PHQ-9 performed better as a whole, as it provided more information than the other scales on the broadest range of depression severity, and it did not contain items with inefficient choices. The CES-D may also be a good choice when sampling students with elevated levels of depressive symptoms. Finally, we linked the 3 instruments on a common scale using parameters derived from IRT analysis, and we provided a crosswalk table to enable the conversion of each scale score. (PsycINFO Database Record