The yin and yang of neuroinflammation: in search for novel neuroprotective and regenerative molecules.

Acute inflammation was recently reported to enhance neurogenesis in the adult zebrafish CNS after stab injury. Based on these findings and recent data suggesting a beneficial effect of acute microglia reactivation/macrophage infiltration on RGC regenerative responses in the zebrafish retinotectal system, we hypothesize that a controlled induction and subsequent resolution of neuroinflammation largely underlies the successful regenerative properties of the severed zebrafish CNS. Furthermore, although aging is clearly a multifactorial process, it is typically accompanied by so-called inflammaging, a stress-induced chronic low-grade inflammation in the entire CNS. Recently, the zebrafish was put forward as a promising model to study gradual senescence and CNS aging, but the regenerative capacity of the aging zebrafish retina and CNS is yet to be investigated. Based on preliminary data, we hypothesize that the aged zebrafish retinotectal system, characterized by a low-grade inflammatory status, shows a reduced regenerative capacity and functional recovery. In this project we aim at shedding light on how acute and chronic neuroinflammatory processes contribute to neuronal survival and axonal regeneration and at investigating whether modulation of underlying molecules or pathways can lead to increased neuroprotection or regeneration. Thereto, we will use a combination of state-of-the-art molecular, biochemical, morphological, functional and behavioral tools, in two vertebrates with different strengths, zebrafish and mice. We believe the zebrafish model provides a unique opportunity for identifying key molecular signaling pathways and biologically active molecules associated with CNS injury that are required to promote neuronal survival and axonal regeneration, but that are missing (or dysfunctional) in mammals.

Keywords:Zebrafish, Neuroinflammation, Mice, Axonal Regeneration, Visual System

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences, Other biological sciences