Apelin Deficiency Accelerates the Progression of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motor neurons. Recent studies have implicated that chronic hypoxia and insufficient vascular endothelial growth factor (VEGF)-dependent neuroprotection may lead to the degeneration of motor neurons in ALS. Expression of apelin, an endogenous ligand for the G protein-coupled receptor APJ, is regulated by hypoxia. In addition, recent reports suggest that apelin protects neurons against glutamate-induced excitotoxicity. Here, we examined whether apelin is an endogenous neuroprotective factor using SOD1G93A mouse model of ALS. In mouse CNS tissues, the highest expressions of both apelin and APJ mRNAs were detected in spinal cord. APJ immunoreactivity was observed in neuronal cell bodies located in gray matter of spinal cord. Although apelin mRNA expression in the spinal cord of wild-type mice was not changed from 4 to 18 weeks age, that of SOD1G93A mice was reduced along with the paralytic phenotype. In addition, double mutant apelin-deficient and SOD1G93A displayed the disease phenotypes earlier than SOD1G93A littermates. Immunohistochemical observation revealed that the number of motor neurons was decreased and microglia were activated in the spinal cord of the double mutant mice, indicating that apelin deficiency pathologically accelerated the progression of ALS. Furthermore, we showed that apelin enhanced the protective effect of VEGF on H2O2-induced neuronal death in primary neurons. These results suggest that apelin/APJ system in the spinal cord has a neuroprotective effect against the pathogenesis of ALS

The Association of Current Violence from Adult Family Members with Adolescent Bullying Involvement and Suicidal Feelings.

Although several studies have reported that child physical abuse increased the risk for bullying involvement, the effect of current violence from adult family members (CVA) on bullying involvement and suicidal feelings among adolescents has not been sufficiently examined. This study investigated the association of CVA with adolescent bullying involvement and the interaction effect of CVA and bullying involvement on suicidal feelings. This cross-sectional study used data from a school-based survey with a general population of adolescents (grades 7 to 12). Data were collected using a self-report questionnaire completed by 17,530 students. Logistic regression analyses were performed to explore the association of CVA with adolescent bullying involvement and suicidal feelings. The overall response rate was 90.2%. The odds of students being characterized as bullies, victims, and bully-victims were higher among adolescents with CVA than without CVA (odds ratios (OR) = 2.9, 95% confidence interval (CI), [2.3-3.7], 4.6 [3.6-5.8], and 5.8 [4.4-7.6], respectively). Both CVA (OR = 3.4 [95% CI 2.7-4.3]) and bullying (bullies, victims, and bully-victims; OR = 2.0 [95% CI 1.6-2.6], 4.0 [3.1-5.1], 4.1 [3.0-5.6], respectively), were associated with increased odds of current suicidal feelings after adjusting for confounding factors. Furthermore, positive additive effects of CVA and all three types of bullying involvement on suicidal feelings were found. For example, bully-victims with CVA had about 19-fold higher odds of suicidal feelings compared with uninvolved adolescents without CVA. This study, although correlational, suggested that CVA avoidance might prevent bullying involvement and suicidal feelings in adolescents

RP58 regulates the multipolar-bipolar transition of newborn neurons in the developing cerebral cortex

SummaryAccumulating evidence suggests that many brain diseases are associated with defects in neuronal migration, suggesting that this step of neurogenesis is critical for brain organization. However, the molecular mechanisms underlying neuronal migration remain largely unknown. Here, we identified the zinc-finger transcriptional repressor RP58 as a key regulator of neuronal migration via multipolar-to-bipolar transition. RP58−/− neurons exhibited severe defects in the formation of leading processes and never shifted to the locomotion mode. Cre-mediated deletion of RP58 using in utero electroporation in RP58flox/flox mice revealed that RP58 functions in cell-autonomous multipolar-to-bipolar transition, independent of cell-cycle exit. Finally, we found that RP58 represses Ngn2 transcription to regulate the Ngn2-Rnd2 pathway; Ngn2 knockdown rescued migration defects of the RP58−/− neurons. Our findings highlight the critical role of RP58 in multipolar-to-bipolar transition via suppression of the Ngn2-Rnd2 pathway in the developing cerebral cortex