B23/Nucleophosmin promotes reconstitution of synaptic path in hippocampus after injury.

B23, also known as nucleophosmin (NPM), is multifunctional protein directly implicated in cell proliferation, cell cycle progression, and cell survival. In the current study, in addition to confirming its anti-apoptotic function in neuronal survival, we demonstrated that the spatial-temporal expression profile of B23 during development of hippocampal neurons is high in the embryonic stage, down-regulated after birth, and preferentially localized at the tips of growing neuritis and branching points. Overexpression of B23 promotes axon growth with abundant branching points in growing hippocampal neurons, but depletion of B23 impairs axon growth, leading to neuronal death. Following injury to the trisynaptic path in hippocampal slice, overexpression of B23 remarkably increased the number and length of regenerative fibers in the mossy fiber path. Our study suggests that B23 expression in developing neurons is essential for neuritogenesis and axon growth and that up-regulation of B23 may be a strategy for enhancing the reconstitution of synaptic paths after injury to hippocampal synapses.

Serial Progression from Attention-Deficit/Hyperactivity Disorder to Alcohol Use Disorder: Serial Multiple Mediated Effects of Externalizing Disorders and Depression.

OBJECTIVE: Externalizing disorders such as attention-deficit/hyperactivity disorder (ADHD), conduct disorder and antisocial personality disorder, as well as depression are common comorbidities in alcohol use disorder (AUD). The current study focused on the temporal relationship between the onsets of these disorders and AUD, and investigated the serial multiple mediator model of externalizing disorders (e.g., ADHD) and depression on AUD. METHODS: We analyzed the mediated effects of the Adult ADHD Self-Report Scale (ASRS), the Barratt Impulsiveness Scale motor (BIS_M) and the Beck Depression Inventory (BDI) on Korean version of the Alcohol Dependence Scale (ADS_K) using the multiple-step multiple mediation procedure regression analysis. In addition, we comparatively analyzed different clinical characteristics in relation to conduct problems. RESULTS: The multiple-step multiple mediation procedure found the serial multiple mediated effects of the BIS_M and the BDI on the relationship between the ASRS and the ADS_K. Also, the group with conduct problem was significantly high in ADHD symptoms, depression, anxiety, impulsivity, legal problems and alcohol-related problems, compared to the group without conduct problems. CONCLUSION: To sum up, the results of this study show that ADHD symptoms in childhood could exert significant effects on the severity of AUD in adulthood, and both disorders might be mediated by the externalizing disorders characterized by the core feature of motor impulsivity, and depression serially. Thus, the treatment of preceding disorders in accordance with developmental stages is an overarching clinical component for preventing the subsequent development of AUD and for its treatment.