Involvement of Bradykinin Receptor 2 in Nerve Growth Factor Neuroprotective Activity

Cells

Roberta Possenti¹  Sonia Piccinin²  Robert Nisticò²  Sebastiano Cavallaro³  Carla Petrella⁴  Delio Mercanti⁴  Cinzia Severini⁴  MariaTeresa Ciotti⁴  Pietro Calissano⁵  Simona Capsoni⁶ 

[1] Department Medicine of Systems, University of Rome “Tor Vergata”, Via della Ricerca Scientifica 1, 00133 Rome, Italy;Department of Biology, University of Rome “Tor Vergata”, Via della Ricerca Scientifica 1, 00133 Rome, Italy;Institute for Biomedical Research and Innovation, National Research Council, Via Paolo Gaifami 18, 95126 Catania, Italy;Institute of Biochemistry and Cell Biology, National Research Council, Sapienza University of Rome, Viale del Policlinico, 155-00161 Rome, Italy;Rita Levi-Montalcini European Brain Research Institute (EBRI), Viale Regina Elena, 295, 00161 Rome, Italy;Section of Physiology, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy;

关键词: nerve growth factor (NGF);    bradykinin receptor 2 (B2R);    microglial cells;    LTP;    Alzheimer’s disease animal models;   

DOI  :  10.3390/cells9122651

来源: DOAJ

【 摘 要 】

Neurotrophin nerve growth factor (NGF) has been demonstrated to upregulate the gene expression of bradykinin receptor 2 (B2R) on sensory neurons, thus facilitating nociceptive signals. The aim of the present study is to investigate the involvement of B2R in the NGF mechanism of action in nonsensory neurons in vitro by using rat mixed cortical primary cultures (CNs) and mouse hippocampal slices, and in vivo in Alzheimer’s disease (AD) transgenic mice (5xFAD) chronically treated with NGF. A significant NGF-mediated upregulation of B2R was demonstrated by microarray, Western blot, and immunofluorescence analysis in CNs, indicating microglial cells as the target of this modulation. The B2R involvement in the NGF mechanism of action was also demonstrated by using a selective B2R antagonist which was able to reverse the neuroprotective effect of NGF in CNs, as revealed by viability assay, and the NGF-induced long-term potentiation (LTP) in hippocampal slices. To confirm in vitro observations, B2R upregulation was observed in 5xFAD mouse brain following chronic intranasal NGF treatment. This study demonstrates for the first time that B2R is a key element in the neuroprotective activity and synaptic plasticity mediated by NGF in brain cells.

【 授权许可】

Unknown