Bone morphogenetic proteins (BMP6 and BMP7) enhance the protective effect of neurotrophins on cultured septal cholinergic neurons during hypoglycemia.

The effects of two bone morphogenetic proteins (BMP6, BMP7), alone and in combination with neurotrophins, were tested on cultures of embryonic day 15 rat septum. A week-long exposure to BMP6 or BMP7 in the optimal concentration range of 2-5 n M increased the activity of choline acetyltransferase (ChAT) by 1.6-2-fold, in both septal and combined septal-hippocampal cultures. The increase in ChAT activity reached significance after 4 days and continued to increase over an 11-day exposure. Under control culture conditions neither BMP significantly altered the number of cholinergic neurons, and BMP effects on ChAT activity were less than linearly additive with those of nerve growth factor. The effects of BMPs and BMP + neurotrophin combinations were also assayed under two stress conditions: low-density culture and hypoglycemia. In low-density cultures BMPs and BMP + neurotrophin combinations preserved ChAT activity more effectively than neurotrophins alone. During 24 h hypoglycemic stress, BMPs alone did not preserve ChAT activity, but BMP + neurotrophin combinations preserved ChAT activity much more effectively than neurotrophins alone. These results demonstrate that BMP6 and BMP7 enhance ChAT activity under control and low-density stress conditions, and that during a hypoglycemic stress their trophic effect requires and complements that exerted by neurotrophins.