ABSTRACT
Parvalbumin (PV) positive interneurons in the subgranular zone (SGZ) can regulate adult hippocampal neurogenesis. ErbB4 is mainly expressed in PV neurons in the hippocampus and is crucial for keeping normal function of PV neurons. However, whether ErbB4 in PV interneurons affects the adult hippocampal neurogenesis remains unknown. In the present study, we deleted ErbB4 specifically in PV neurons by crossing PV-Cre mice with ErbB4f/f mice. Results of BrdU labeling and NeuN staining revealed that the proliferation of neural progenitors was increased but the survival and maturation of newborn neurons were decreased in the hippocampus of mice after deleting ErbB4 in PV neurons, suggesting that ErbB4 in PV neurons is closely associated with the process of adult hippocampal neurogenesis. Interestingly, the expression of brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), was significantly decreased in the hippocampus of ErbB4-deleted mice. Together, our data suggested that ErbB4 in PV neurons might modulate adult hippocampal neurogenesis by affecting BDNF-TrkB signaling pathway.
Subject(s)
Brain-Derived Neurotrophic Factor/genetics , Hippocampus/cytology , Interneurons/physiology , Membrane Glycoproteins/genetics , Neurogenesis/genetics , Neurogenesis/physiology , Parvalbumins/metabolism , Protein-Tyrosine Kinases/genetics , Receptor, ErbB-4/genetics , Animals , Behavior, Animal/physiology , Brain-Derived Neurotrophic Factor/physiology , Cell Survival , Down-Regulation , Gene Deletion , Membrane Glycoproteins/physiology , Mice , Mice, Knockout , Neural Stem Cells/physiology , Protein-Tyrosine Kinases/physiology , Signal Transduction/genetics , Signal Transduction/physiologyABSTRACT
Cellular senescence is a growth-arrest program that limits cell proliferation. Low-power laser irradiation (LPLI) has been demonstrated to promote cell proliferation. However, whether LPLI can inhibit cellular senescence remains unknown. In the present study, to investigate the functional role of LPLI against skin aging, we used ultraviolet radiation b (UVB) to induce cell senescence. We first report that LPLI can delay UVB-induced cell senescence. The senescence-associated ß-galactosidase (SA-ß-Gal) activity and p21 expression, hallmarks of senescent cells, were decreased in the Forkhead box transcription factor FOXM1-dependent manner under treatment with LPLI. The effect of LPLI was further enhanced with an overexpression of FOXM1, and abolished when FOXM1 was knockdown with short hairpin RNA (shRNA). Furthermore, LPLI activated the extracellular regulated protein kinases (ERK) that was upstream of FOXM1. This led to FOXM1 phosphorylation and nuclear translocation. Nuclear translocation enhanced FOXM1 transcriptional activity and promoted its downstream target gene c-Myc expression that could inhibit p21 expression. These findings highlight the protective effects of ERK/FOXM1 pathway against UVB-induced cell senescence, suggesting a potential protecting strategy for treating skin aging by LPLI.
