Developmental expression of the beta-amyloid precursor protein and heat-shock protein 70 in the cerebral hemisphere region of the rat brain.
Alzheimer's disease (AD) is characterized by depositions of the amyloid beta protein (A beta) in the brain in the form of extracellular plaques and cerebrovascular amyloid. A beta (approximately 4 kDa) is derived from a family of large (approximately 110 kDa) beta-amyloid precursor proteins (APP), which are integral membrane glycoproteins. Although a connection between AD and alcoholism has recently been suggested, this relationship has not been explored at the molecular level. Our hypothesis is that APP has a role in brain development and that abnormal APP levels may be involved in dementia associated with AD and alcoholism. We compared the profile of total APP levels between ethanol naïve alcohol-preferring (P) and alcohol-nonpreferring (NP) rats. We also investigated the possibility that APP levels can be regulated in an age-dependent manner in young rats. We studied the distribution of two proteins in the cerebral hemisphere region of the rat brain at various developmental periods. Six groups composed of the following different ages of rats were used: 7, 14, 21, 36, 43, and 78 (postnatal) days. Cell extracts from different regions of the brain were subjected to Western immunoblotting using mAb22C11. Our results suggest that levels of high-molecular-weight APP bands were greater in brain extracts from 7-day-old P rats than in other samples tested, and that the distribution of APP levels was more uneven in brain extracts from different ages of P than from NP rats. These initial results suggest that APP may play an important role in the early development of the rat brain and the alcohol-preferring trait may influence APP processing in the developing brain.
Lahiri
D K
DK
Laboratory of Molecular Neurogenetics, Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana 46202-4887, USA. dlahiri@iupui.edu
Nall
C
C
Chen
D
D
Zaphiriou
M
M
Morgan
C
C
Nurnberger
J I
JI
D000428:Alcohol Drinking; D000544:Alzheimer Disease / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D016564:Amyloid beta-Protein Precursor; D018840:HSP70 Heat-Shock Proteins