Involvement of the α7 subunit of the nicotinic receptor in morphogenic and trophic effects of acetylcholine on embryonic rat spinal motoneurons in culture

✍ Scribed by Christelle Catone; Jean-Pierre Ternaux

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 241 KB
• Volume: 72
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.10550

✦ Synopsis

Abstract

The morphogenic and trophic effects of acetylcholine (ACh) on embryonic cultured rat spinal cord motoneurons (MNs) through nicotinic α7 autoreceptors were assessed. α7 Subunits of the nicotinic cholinergic receptor were detected in cultures of purified rat spinal embryonic MNs sampled at E15, by both immunocytochemistry and α‐bungarotoxin binding. According to these two methods, α7 subunits are located mainly at somatic and axonal membrane. Functional involvement of the α7 subunit in survival and development of morphological properties of growing cultured MNs was tested using an antisense strategy. The antisense oligonucleotide significantly decreases the expression of the α7 protein compared with control and mismatch oligonucleotide‐treated cultures. This decrease in the expression of the α7 protein leads to a significant increase in the number of axonal branches and in the length of the axon. The antisense treatment also induces, as early as the first day in culture, a decrease of MN survival, leading to total cell death at day 5. TUNEL staining revealed that the MNs are dying through apoptotic processes. Thus, our study shows that ACh is a morphogenic and trophic factor. These effects are directly linked to the membrane expression level of α7 protein. Indeed, the lower the α7 expression, the lower the inhibition of axonal growth (i.e., axonal elongation) and the lower the MN survival. © 2003 Wiley‐Liss, Inc.