Cultured dorsal root ganglion (DRG) neurons from fetal trisomy 19 mice showed no difference in electrical membrane properties compared to neurons from littermate controls, indicating that these parameters are not altered generally in trisomies. DRG neurons transgenic for the human gene for superoxide dismutase (found on human chromosome 21 and mouse chromosome 16) showed no significant difference in action potential parameters compared to control cells, indicating that excess dosage of this gene alone does not underlie abnormalities identified in trisomy 16 and trisomy 21 neurons. In replated trisomy 21 fetal neurons, voltage clamp studies identified tetrodotoxin-sensitive and slow tetrodotoxin-insensitive sodium currents, the latter accounting for 90% of the total charge moving across the membrane. No alterations in maximal conductances were observed. The slow sodium component had slowed deactivation kinetics. Inactivation curves for both fast and slow currents were shifted 10 mV in the depolarizing direction in trisomy 21 neurons, resulting in a greater number of sodium channels available for activation. Nerve growth factor (NGF) was shown to be essential for the survival of human fetal neurons in culture, but not responsible for the differences in electrical membrane properties observed between trisomy 21 and control neurons. Fetal brain tissue from the trisomy 16 mouse was shown to survive for 14-24 weeks after being grafted into host mouse brain, thus providing a possible animal model of Alzheimer's disease. Fluorescence studies of catecholamines suggested that trisomy 16 neurons have abnormal neurotransmitter-uptake.
