| Abstrakt: |
Objective: Neurite outgrowth, the first and fundamental step in axonal and dendritic development in neurones, is an essential process for nervous system development, its plasticity and formation of synaptic connections. Inducing neurite outgrowth and increasing neuronal survival are important strategies to treat neurodegenerative diseases. Sigma-1 receptor (Sig-1R) is a molecular chaperone which is located mitochondria-related endoplasmic reticulum membrane. Sig-1R plays a vital role in several cellular processes, for example neurite outgrowth, neuronal plasticity, Ca+2 transport from ER to mitochondria, neuroprotection. The aim of this study is to investigate the possible effects of cutamesin (SA4503), a selective Sig-1R agonist, in neurite outgrowth and to search the interaction between Sig- 1R and inositol 1,4,5-trisphosphate receptor (IP3-R). Methods: Primary hippocampal neuron culture, isolated from neonatal BalbC (n=20) mice, was used as an in vitro model. The presence of Sig-1R in hippocampal neurons was investigated by immnunocytochemistry in confocal microscopy and by western blotting of total protein extracts from hippocampal cell culture. Cells were seeded in petri dishes and cutamesin was applied in most effective dose (10 μM) determined previously. NE100 (10 μM), Sig-1R antagonist, and Xestospongin C (1 μM), an IP3-R antagonist, were added to cell culture before cutamesin application. Neurites were labeled in confocal microscopy by using beta III tubulin antibody. The percentage of neurite containing neurons was calculated from microscopy images and data were statistically evaluated by one-way ANOVA test. Results: Cutamesin increased neurite outgrowth in primary hippocampal neurons significantly (p<0.001). On the other hand, applications of NE100 and Xestospongin C decreased the cutamesin induced neurite outgrowth significantly (p<0.001). Conclusion: Our findings showed for the first time in primary hippocampal neurons that cutamesin elevates neurite outgrowth, whereas inhibition of IP3-R decreases it. We concluded that Sig- 1R has a positive effect on neurite outgrowth and this effect is mediated by regulating Ca+2 transport between ER and mitochondria. [ABSTRACT FROM AUTHOR] |
