ABSTRACT
The expression of chemokine receptors and chemokine production by adult human non-transformed astrocytes, grade III astrocytoma and grade IV glioblastoma tumour cell lines were determined. Here, we show an increased expression of CXCR3 and CXCR4, and a decreased expression of CXCR1 and CCR4 by glioma cells compared to adult human astrocytes. Glioma cells showed increased production of CXCL10, whereas production of other chemokines was decreased (CXCL8, CCL2, CCL5, and CCL22). CXCL10 induced an ERK1/2-dependent increase in [(3)H] thymidine uptake. These results suggest that expression of chemokine receptor/ligand pairs such as CXCR3/CXCL10 have an important role in the proliferation of glioma cells.
Subject(s)
Cell Proliferation , Chemokine CXCL10/biosynthesis , Chemokines/biosynthesis , Glioma/metabolism , Receptors, Chemokine/biosynthesis , Astrocytes/metabolism , Blotting, Western , Cell Line, Tumor , Electrophoresis, Polyacrylamide Gel , Enzyme-Linked Immunosorbent Assay , Extracellular Signal-Regulated MAP Kinases/metabolism , Flow Cytometry , Gene Expression , Humans , RNA, Messenger , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Long-term memory is dependent on protein synthesis and inhibiting such synthesis following training results in amnesia for the task. Proteins synthesized during training must be transported to the synapse and disrupting microtubules with Colchicines, and hence, blocking transport, results in transient amnesia. Reactivating memory for a previously learned avoidance triggers a biochemical cascade analogous to that following the initial training and renders the memory labile once more to protein synthesis inhibitors. However, the reminder-induced cascade differs in certain key features from that following training. Here we show that in a one-trial passive avoidance task in chicks, in contrast with initial consolidation following training, memory following a reminder is not impaired by Colchicine. We conclude that recall after a reminder does not require synaptic access to somatically synthesized proteins in this task. Our results support the hypothesis that in the chick, a reminder may instead engage local protein synthesis at the synapse, rather than in the soma.
Subject(s)
Amnesia/metabolism , Avoidance Learning/physiology , Discrimination Learning/physiology , Mental Recall/physiology , Protein Biosynthesis/physiology , Amnesia/chemically induced , Analysis of Variance , Animals , Avoidance Learning/drug effects , Chickens , Colchicine , Cues , Discrimination Learning/drug effects , Mental Recall/drug effects , Protein Biosynthesis/drug effects , Protein Synthesis Inhibitors , Synapses/drug effects , Synapses/physiology , Time FactorsABSTRACT
The amyloid precursor protein (APP) has been shown to be implicated in age-associated plastic changes at synapses that might contribute to memory loss in Alzheimer's disease. As APP has previously been reported to have multiple functions during normal development, and as human and avian APP share 95% homology in amino acid sequence, we have employed a one-trial passive avoidance task in day-old chicks to study its role in the process of memory formation. Administration of anti-APP antibodies, raised against human APP, APP-antisense, and Abeta during pre-training, prevented memory formation without effects on general behavior or initial acquisition. Amnesia is apparent by 30 min post-training and lasts for at least 24 hours. Injection of APP-derived peptides RERMS (APP(328-332)) and RER (APP(328-330)) homologous to the short stretches of amino acids in the Kang sequence (APP(319-335)), rescue the memory in animals rendered amnestic by previous (anti-APP antibody, antisense, and Abeta pretreatments. The protected form of RER, with a prolonged half-life (acetylated RER), proved to be effective when injected intracranially and peripherally. The tripeptide RER exerts its biological activity by binding to two neuronal plasma membrane proteins (60 and 110 kDa). The results obtained in this study suggest that RER alleviates memory deficits via receptor-mediated events, and that short APP-derived peptides might represent a novel group of therapeutically active molecules for the alleviation of memory deficits in age-related dementias.
