BRAIN-DERIVED PROTEINS THAT RESCUE SPINAL MOTONEURONS FROM CELL-DEATHIN THE CHICK-EMBRYO - COMPARISONS WITH TARGET-DERIVED AND RECOMBINANTFACTORS

Spinal motoneurons that normally die during early development can he r escued by a variety of purified growth or neurotrophic factors and tar get tissue extracts. There is also indirect evidence that brain or sup raspinal afferent input may influence lumbar motoneuron survival durin g development and that this effect may be mediated by central nervous- system-derived trophic agents. This report examines the biological and biochemical properties of motoneuron survival activity obtained from extracts bf the embryonic chick brain. Treatment with an ammonium sulf ate (25% to 75%) fraction of embryonic day 16 (E16) or E10 brain extra cts rescued many spinal motoneurons that otherwise die during the norm al period of cell death in vivo (E6 to E10). The same fractions also e nhanced lumbar motoneuron survival following deafferentation. There we re both similarities and differences between the active fractions deri ved from brain extracts (BEX) when compared with extracts derived from target muscles (MEX) or with purified neurotrophic factors. Survival activity from E10 BEX was as effective in promoting motoneuron surviva l as E10 MEX and more effective than astrocyte-conditioned media. Unli ke MEX, the active fractions from BEX also rescued placode-derived nod ose ganglion cells. In addition, unlike nerve growth factor and brain- derived neurotrophic factor, active BEX fractions did not rescue neura l crest-derived dorsal root ganglion cells or sympathetic ganglion neu rons. Interestingly, among many cranial motor and other brainstem nucl ei examined, only the survival of motoneurons from the abducens nucleu s was enhanced by BEX. Active proteins obtained from BEX were further separated by gel filtration chromatography and by preparative isoelect ric focusing techniques. Activity was recovered in a basic (pI 8) and an acidic (pI 5) small molecular weight protein fraction (20 kD or les s). The specific activity of the basic fraction was increased X66 when compared with the specific activity of crude BEX, and the basic fract ion had a slightly higher specific activity than the acidic fraction. The biological and biochemical properties of these fractions are discu ssed in the context of known neurotrophic factors and their effects on normal and lesion-induced motoneuron death during development. (C) 19 95 John Wiley and Sons, Inc.