Microglia activation during neuroregeneration in the adult vertebrate brain.

Brain injury and neuronal loss leads to an inflammatory response, which is initiated by the innate immune system. To what extent this immune response is beneficial or detrimental for neurogenesis and regeneration is unclear. We addressed this question during regeneration of dopamine neurons in the adult salamander brain. In contrast to mammals, ablation of dopamine neurons evokes robust neurogenesis leading to complete histological and functional regeneration within four weeks in salamanders. Here we show that similarly to mammals, ablation of dopamine neurons causes microglia activation and an increase in microglia numbers in the ablated areas. Furthermore, microglia numbers remain elevated compared to the uninjured brain at least six weeks after ablation. Suppression of the microglia response results in enhanced regeneration, concomitant with reduced death of dopamine neurons during the regeneration phase. Thus neuroregeneration is not dependent on the absence of an innate immune response, but the suppression of this response may be a means to promote neurogenesis in the adult vertebrate brain.