Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 7708769

Inflammatory processes induce beta-amyloid precursor protein changes in mouse brain.

B Brugg·Y L Dubreuil·G Huber·E E Wollman·N Delhaye-Bouchaud·J Mariani
View original source ↗Export metadata ↓

Abstract

In Alzheimer disease, a combination of genetic predisposition and environmental factors may contribute to changes in beta-amyloid precursor protein (APP) expression, beta-amyloid peptide deposition, and neuronal loss. Factors such as head injury or acute infection that trigger inflammatory processes may play a crucial role in development of the disease. In the present in vivo study, we showed that, in mouse brain, peripheral stimulation with lipopolysaccharide (LPS) induced a transient increase in the inflammatory cytokine mRNAs (interleukin 1 beta and interleukin 6), followed by changes in expression of APP isoforms in the cerebellum but not in the cerebral cortex. These changes consisted of a decrease in the APP-695 and an increase in the Kunitz protease inhibitor-bearing isoforms (KPI-APP). In the cerebellum of the staggerer mouse mutant, where a severe loss of Purkinje and granule cells occurs, basal mRNA levels of these interleukins were elevated and an increase in the KPI-APP/APP-695 ratio compared to wild-type mice was observed. These abnormalities were further accentuated by LPS stimulation. This study shows that acute and chronic inflammatory processes play an important role in changes in APP expression possibly associated with neurodegeneration.

Explore related subjects

Amyloid beta-Protein PrecursorAnimalsBlotting, WesternBrainCerebellumCerebral CortexCrosses, GeneticInflammationInterleukin-6KineticsLipopolysaccharidesMiceMice, Inbred C57BLMice, Neurologic MutantsPolymerase Chain ReactionRNA, MessengerReference ValuesTime FactorsComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

B Brugg, Y L Dubreuil, G Huber, E E Wollman, N Delhaye-Bouchaud, J Mariani. 1995-03-28. Inflammatory processes induce beta-amyloid precursor protein changes in mouse brain.. https://doi.org/10.1073/pnas.92.7.3032

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

The low-density lipoprotein receptor-related protein 1 (LRP1) mediates the endocytosis of the cellular prion protein.

PrP(C) (cellular prion protein) is located at the surface of neuronal cells in detergent-insoluble lipid rafts, yet is internalized by clathrin-dependent endocytosis. As PrP(C) is glycosyl-phosphatidylinositol-anchored, it requires a transmembrane adaptor protein to connect it to the clathrin endocytosis machinery. Using receptor-associated protein and small interfering RNA against particular LDL (low-density lipoprotein) family members, in combination with immunofluorescence microscopy and surface biotinylation assays, we show that the transmembrane LRP1 (LDL receptor-related protein 1) is required for the Cu(2+)-mediated endocytosis of PrP(C) in neuronal cells. We show also that another LRP1 ligand that can cause neurodegenerative disease, the Alzheimer's amyloid precursor protein, does not modulate the endocytosis of PrP(C).

Amyloid beta-Protein Precursor↗
PubMed2006

Neurobehavioral functional deficits following closed head injury in the neonatal pig.

Neurobehavioral deficits in higher cortical systems have not been described previously in a large animal model of diffuse brain injury. Anesthetized 3-5 day old piglets were subjected to either mild (142 rad/s) or moderate (188 rad/s) rapid non-impact axial rotations of the head. Multiple domains of cortical function were evaluated 5 times during the 12 day post-injury period using tests of neurobehavioral function devised for piglets. There were no observed differences in neurobehavioral outcomes between mild injury pigs (N=8) and instrumented shams (N=4). Moderately injured piglets (N=7) had significantly lower interest in exploring their environment and had higher failure rates in visual-based problem solving compared to instrumented shams (N=5) on days 1 and 4 after injury. Neurobehavioral functional deficits correlated with neuropathologic damage in the neonatal pigs after inertial head injury. Injured axons detected by immunohistochemistry (beta-APP) were absent in mild injury and sham piglets, but were observed in moderately injured piglet brains. In summary, we have developed a quantitative battery of neurobehavioral functional assessments for large animals that correlate with neuropathologic axonal damage and may have wide applications in the fields of cardiac resuscitation, stroke, and hypoxic-ischemic brain injury.

Amyloid beta-Protein Precursor↗
PubMed2006

Rat brain synaptic vesicles are devoid of Mg2+-ATPase activity and contain beta-amyloid precursor protein.

Rat brain synaptic vesicles (SVs) isolated by gel filtration on Sephacryl S-500 had little Mg2+(H+)-ATPase activity, though it was identified by Western blots with antibodies against the H+-ATPase A-subunit and other vesicle proteins. In contrast, tyrosine hydroxylase and dopa decarboxylase activities in the SVs were substantial, suggesting that the absence of Mg2+(H+)-ATPase activity was not due to inactivation during isolation but rather to the nature of the SVs. The vesicle component reactive to H+-ATPase antibody was also identified in the synaptosomal cytosol, so the antibody for the A-subunit seemed unnecessary to detect H+-ATPase. The SVs contained beta-amyloid precursor protein of approximately 100 kDa. Based on these observations, SVs without Mg2+(H+)-ATPase seemed to play a role(s) in the delivery of cytoplasmic and plasma membrane proteins to nerve terminals as well as in neurotransmission.

Amyloid beta-Protein Precursor↗