E. Vanuden et al., A NOVEL ROLE FOR RECEPTOR-ASSOCIATED PROTEIN IN SOMATOSTATIN MODULATION - IMPLICATIONS FOR ALZHEIMERS-DISEASE, Neuroscience, 88(3), 1999, pp. 687-700
Receptor-associated protein appears to play an important role in low-d
ensity lipoprotein receptor-related protein trafficking. Since ligands
for the low-density lipoprotein receptor-related protein have been im
plicated in Alzheimer's disease and normal Functioning of this protein
is indispensable for central nervous system development, deficient re
ceptor-associated protein expression may result in central nervous sys
tem alterations. In this study, receptor-associated protein knockout m
ice were behaviorally tested and nervous system integrity was assessed
via in situ hybridization and immunocytochemical/laser confocal micro
scopy methods. Receptor-associated protein knockout mice were found to
be cognitively impaired in the Morris water maze compared to controls
. In wild-type mice, the receptor-associated protein was found to be h
ighly co-expressed with somatostatin in hippocampal and neocortical in
hibitory neurons. Receptor-associated protein knockout mice, however,
showed a significant decrease in number of somatostatin-expressing neu
rons of the CA1 region and somatostatin expression within these neuron
s. The decreased number of somatostatin neurons significantly correlat
ed with cognitive impairment observed in the receptor-associated prote
in knockout mice. These results suggest a novel role for receptor-asso
ciated protein in modulating the functioning of somatostatin-producing
neurons. Further more, this has implications for Alzheimer's disease
pathogenesis, in which altered regulation of both somatostatin and the
known low-density lipoprotein receptor-related protein ligands are a
consistent finding. (C) 1998 IBRO. Published by Elsevier Science Ltd.