p11 mediates the BDNF-protective effects in dendritic outgrowth and spine formation in B27-deprived primary hippocampal cells

• DOI: 10.1016/j.jad.2016.02.010
• Publication Date: 2016-02-09T07:16:46Z
• Authors: Sung Woo Park; Le Hoa Nhu; Hye Yeon Cho; Mi Kyoung Seo; Chan Hong Lee; Nguyen Ngoc Ly; Cheol Min Choi; Bong Ju Lee; Gyung-Mee Kim; Wongi Seol; Jung Goo Lee; Young Hoon Kim
• Keywords: 0301 basic medicine; Mice; 03 medical and health sciences; Neuronal Plasticity; Depression; Brain-Derived Neurotrophic Factor; S100 Proteins; Animals; Dendrites; Hippocampus; Annexin A2; Antidepressive Agents

p11 (S100A10) is a key regulator of depression-like behaviors and antidepressant drug response in rodent models. Recent studies suggest that p11 mediates the behavioral antidepressant action of brain-derived neurotrophic factor (BDNF) in rodents. BDNF improves neural plasticity, which is linked to the cellular actions of antidepressant drugs. In the present study, we investigated whether p11 regulated BDNF action on neural plasticity in vitro.We generated primary hippocampal cultures. p11 expression, total dendritic length, and spine density were investigated under toxic conditions induced by B27 deprivation, which causes hippocampal cell death.B27 deprivation significantly decreased p11 expression. Treatment with BDNF significantly prevented the B27 deprivation-induced decrease in p11 levels in a concentration-dependent manner, whereas these concentrations had no effect on control cultures. B27 deprivation significantly reduced the total length of hippocampal dendrites and spine density. BDNF increased the total dendritic length and spine density in conditions with or without B27. Furthermore, p11 knockdown through small interfering RNA (siRNA) transfection blocked these effects. The overexpression of p11 in B27-deprived cells increased the total dendritic length and spine density, and treatment with BDNF potentiated these effects.This study should be confirmed in animal models of depression.Taken together, our data suggest that BDNF-induced improvement in neural plasticity may depend on the regulation of p11 in hippocampal cells with B27 deprivation. These results provide evidence to strengthen the theoretical basis of a role for p11 in BDNF-induced antidepressant action.