MUSCLE-DERIVED FACTORS ENHANCE CHOLINERGIC NEURONAL EXPRESSION IN THE CHICK-EMBRYO .1. INOVO STUDIES

The effects of muscle-derived factors were studied in the chick embryo in ovo, during early neuroembryogenesis. Limb muscle extract (LME) administration during embryonic period E1-E7 produced a significant increase in choline acetyltransferase activity of both spinal cord and brain in 8-day-old chick embryos. Similar treatment failed to induce significant change in the GABAergic phenotypes as assessed by the activity of the enzyme glutamic acid decarboxylase. Administration of limb muscle extract at either embryonic days 1-3 or 4-7 produced a significant increase in choline acetyltransferase activity in the brain, indicating that the critical period of limb muscle extract in the brain to be between embryonic days E1 and E7, a period of neuronal proliferation and differentiation in the brain. On the other hand, LME administration produced no effect on spinal cord choline acetyltransferase activity when given at embryonic days 1-3, whereas it produced a marked increase when given at embryonic days 4-7. Thus, the critical period of limb muscle extract effect in the spinal cord appears to be confined to embryonic days E4-E7, a period of neuronal differentiation and cell death in the spinal cord. These findings indicate that the cholinotrophic activity of muscle-derived factors is not limited to the muscle target tissues but have a general effect on cholinergic neurons in the CNS. Whether these cholinotrophic effects are mediated by a common factor or by different factors is still under investigation.