Role of Macrophages and Microglia in Zebrafish Regeneration

Abstract

<jats:p>Currently, there is no treatment for recovery of human nerve function after damage to the central nervous system (CNS), and there are limited regenerative capabilities in the peripheral nervous system. Since fish are known for their regenerative abilities, understanding how these species modulate inflammatory processes following injury has potential translational importance for recovery from damage and disease. Many diseases and injuries involve the activation of innate immune cells to clear damaged cells. The resident immune cells of the CNS are microglia, the primary cells that respond to infection and injury, and their peripheral counterparts, macrophages. These cells serve as key modulators of development and plasticity and have been shown to be important in the repair and regeneration of structure and function after injury. Zebrafish are an emerging model for studying macrophages in regeneration after injury and microglia in neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease. These fish possess a high degree of neuroanatomical, neurochemical, and emotional/social behavioral resemblance with humans, serving as an ideal simulator for many pathologies. This review explores literature on macrophage and microglial involvement in facilitating regeneration. Understanding innate immune cell behavior following damage may help to develop novel methods for treating toxic and chronic inflammatory processes that are seen in trauma and disease.</jats:p>

The immune response is a critical regulator of zebrafish retinal pigment epithelium regeneration

“…Recent studies have converged on immune-related systems as required to resolve damage and stimulate regenerative responses in multiple model organisms and tissue contexts (e.g. (26)(27)(28)(29)(30)(31)(32)), including in the eye (e.g. (33)(34)(35)(36)(37)(38)(39)).…”

Beneficial Roles of Microglia and Growth Factors in MS, a Brief Review

“…A marked increase in BDNF mRNA expression and a slight increase in neurotrophin-4/5 (NT-4/5) levels have been shown in LPS-treated microglia in vitro . These results demonstrate that inflammatory activated microglia have the ability to favor the secretion of GFs and possibly participate in neuronal regeneration and neuroprotection (Var and Byrd-Jacobs, 2020 ). The BDNF receptor is found at the site of MS lesion.…”

Cone Photoreceptor Degeneration and Neuroinflammation in the Zebrafish Bardet-Biedl Syndrome 2 (bbs2) Mutant Does Not Lead to Retinal Regeneration

“…In both mouse and zebrafish, acute retinal injury triggers resident microglia to rapidly migrate and accumulate near the site of injury or disease and release pro-inflammatory cytokines. These microglia release numerous growth factors and inflammatory cytokines that stimulate Müller glia to regenerate lost neurons (Goldman, 2014;Gorsuch and Hyde, 2014;Mitchell et al, 2018Mitchell et al, , 2019. The cone degeneration observed in zebrafish bbs2 −/− mutants triggers a significant inflammatory response but this is not sufficient to initiate a regenerative response from the Müller glia.…”

“…Inflammatory Response in bbs2 −/− Mutants Acute retinal damage triggers a significant inflammatory response characterized by activated immune cells and reactive Müller glia (White et al, 2017;Mitchell et al, 2018Mitchell et al, , 2019. To determine if ongoing retinal degeneration in bbs2 −/− mutants was associated with elevated inflammation, retinas from 7 mpf animals were stained with the monoclonal antibody 4C4, which is specific for zebrafish microglia (Tsarouchas et al, 2018;Mazzolini et al, 2020), and L-plastin, a pan-leukocyte marker (Herbomel et al, 1999;Le Guyader et al, 2008).…”