A proteomic investigation of forebrain regeneration in the leopard gecko (Eublepharis macularius)

The ability to replace lost or damaged neurons following an injury is termed reactive neurogenesis. Although reactive neurogenesis has been reported in several lizard species, the molecular mechanisms underlying this response remain largely unknown. Here, we investigate ontogenetic, injury-, and regeneration-associated proteomic changes to the forebrain of subadult leopard geckos (Eublepharis macularius), focusing on an area of the cerebral hemispheres that includes the medial and dorsomedial cortices, septum, and neighboring tissues.

Among control (untreated) geckos, the proteome of the forebrain changes during a one-month period, providing evidence of an ontogenetically driven proteomic shift. To initiate reactive neurogenesis, we administered the neurotoxin 3-acetylpyridine (3-AP). Using liquid chromatography-tandem mass spectrometry, we found that 3-AP induces differential expression of proteins associated with cell death, immune activation, and neurogenesis. However, by 30 days post-injury, the proteomic profile of the forebrain was returning toward that of age-matched controls.

Our findings demonstrate that structural regeneration of the gecko forebrain is associated with the differential expression of proteins involved in brain development and repair in mammals and provides a resource for future evolutionary studies of neurogenesis.