How does the brain remove the excess number of neurons during development and aging

Many more neurons are produced during development than are present in the adult brain.

Also many neurons are lost during aging, however the process of innate phagocytosis, which removes unwanted and superfluous neurons is poorly defined. The unwanted neurones enter apoptosis but subsequent clearance of these dying cells is important for our body to avoid autoimmunity or inflammation in the brain. Apoptotic cells express unique markers which enable them to be recognized and engulfed by phagocytes. The knowledge of these unique markers is limited at present to certain cell membrane lipids, e.g. phosphatidylserine. Recent novel finding from our laboratory suggests that a unique protein epitope is expressed early in apoptosis and this is recognized by P2X7 receptors on phagocytes. This project will examine how apoptotic cells are recognized and cleared by phagocytes both in health and in disease. This result will have relevance to many neurological diseases as well as early neurodevelopment.

Techniques involved are cell culture, immunoprecipitation, western blotting, flow cytometry, peptide screen, molecular biology and mass spectrometry.

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