CEREBRAL CORTICAL ASTROGLIA FROM THE TRISOMY-16 MOUSE, A MODEL FOR DOWN-SYNDROME, PRODUCE NEURONAL CHOLINERGIC DEFICITS IN CELL-CULTURE

Trisomy 21 (Down syndrome) is associated with a high incidence of Alzh eimer disease and with deficits in cholinergic function in humans, We used the trisomy 16 (Ts16) mouse model for Down syndrome to identify t he cellular basis for the cholinergic dysfunction, Cholinergic neurons and cerebral cortical astroglia, obtained separately from Ts16 mouse fetuses and their euploid littermates, were cultured in various combin ations, Choline acetyltransferase activity and cholinergic neuron numb er were both depressed in cultures in which both neurons and glia were derived from Ts16 fetuses, Cholinergic function of normal neurons was significantly down-regulated by coculture with Ts16 glia, Conversely, neurons from Ts16 animals could express normal cholinergic function w hen grown with normal glia, These observations indicate that astroglia may contribute strongly to the abnormal cholinergic function in the m ouse Ts16 model for Down syndrome, The Ts16 glia could lack a choliner gic supporting factor present in normal glia or contain a factor that down-regulates cholinergic function.