NEUROPEPTIDE-Y IMMUNOREACTIVE NEURONS IN MURINE TRISOMY-16 CORTICAL CULTURES PLASTICITY OF EXPRESSION AND DIFFERENTIATION

Neuropeptide Y (NPY)-containing neurons are depleted in the cortices o f individuals with Alzheimer disease (AD), yet spared in the striatum of patients with Huntington chorea. It is unknown whether this neurona l phenotype is inherently susceptible to the neurodegenerative process es that are a hallmark of AD. To study this question, the murine triso my 16 model of Down syndrome and Alzheimer disease was investigated. S ince trisomic fetuses die in utero, studies were carried out on primar y cultures of dissociated cortical neurons. These were prepared from 1 5-d gestational trisomy 16 fetuses and their littermate euploid contro ls, and examined by immunocytochemical staining for neuropeptide Y at 7 and 12 d in vitro. Trisomy 16 neurons were also grown on euploid gli al carpets, whereas euploid neurons were grown on trisomic glia. The r esults demonstrate a significant increase in the number of NPY neurons and a stunting in the dendritic arbor of these neurons in trisomic vs euploid cortex. Both of these parameters could be normalized by direc t contact with euploid glia. When euploid cortex was plated on trisomi c glia, the number of NPY neurons and their morphology were altered so that they began to resemble trisomic NPY cortical neurons. These resu lts indicate a dysregulation of NPY neuronal expression and differenti ation in trisomy 16 cortex that are modifiable by interaction with eup loid glia and imply an abnormal trophic (glial) environment in trisomi c cortex.