New neurons for the injured brain: mechanisms of neuronal regeneration in adult teleost fish

Abstract

In contrast to mammals, teleost fish exhibit an enormous potential to continuously produce new neurons in many areas of the adult brain, and to regenerate neural tissue after brain injury. The regenerative capability of the teleost fish brain is based upon a series of well-orchestrated individual processes, including: elimination of damaged cells by apoptosis, removal of cellular debris by the action of microglia/macrophages, proliferation of endogenous neural precursor cells, radial glia-mediated migration of their progeny to the site of the lesion, neuronal differentiation, promotion of cellular survival, and integration of the new neurons into existing neural circuits. Combination of a well-defined cerebellar lesion paradigm with differential proteome analysis has demonstrated that identification of the multitude of proteins mediating the regenerative potential of the adult fish brain is feasible in the foreseeable future. A molecular understanding of brain regeneration in fish could help investigators to define novel strategies to stimulate endogenous neural precursor cells in the mammalian brain to undergo neurogenesis, thus forming the basis of a neuronal replacement therapy for brain injury or neurodegenerative diseases.