PROFILES OF AMYLOID PRECURSOR AND PRESENILIN 2-LIKE PROTEINS ARE CORRELATED DURING DEVELOPMENT OF THE MOUSE HYPOTHALAMUS

The amyloid precursor protein (APP) and APP-like (APLP) material, as v isualized with the Mab22C11 antibody, have previously been shown to be associated with radial glia in hypothalamus, which are known to promo te neurite outgrowth. By Northern blot analysis, APP 695 mRNA levels i ncreased steadily over hypothalamic development, APP 770 mRNA was tran siently expressed at 12 days postnatally, and APLP mRNA was only weakl y expressed in the hypothalamus. The developmental pattern of APP moei ties in mouse hypothalamus and in fetal hypothalamic neurons in cultur e was compared with a presenilin 2 (PS2) related protein using an anti body developed against the N-terminal part of PS2. By Western blot ana lysis, APP and PS2-like immunoreactivity were visualized as a 100-130 and 52 kDa bands, respectively. An APP biphasic increase was observed during hypothalamic development in vivo. APP immunoreactivity was equa lly detected in neuronal and glial cultures, while PS2-like material w as more concentrated in neurons. A correlation between APP/APP-like an d PS2-like levels was observed during development in vivo. While APP w as mostly associated with membrane fractions, a significant portion of PS2-like material was also recovered from cytosolic fractions in vitr o. In contrast to native PS2 in COS-transfected cells, the PS2-like ma terial did not aggregate after heating for 90 s at 90 degrees C. These results indicate a close association between APP and PS2-like materia l during hypothalamic development in vivo, and suggest that neuronal a nd glial cultures may provide appropriate models to test their interac tions.