Immunosuppression promotes endogenous neural stem and progenitor cell migration and tissue regeneration after ischemic injury.

Recent work has demonstrated that self-repair in the adult brain can be augmented by the infusion of growth factors to activate endogenous neural precursor cells that contribute to new tissue formation and functional recovery in a model of stroke. Using both a genetic model and drug treatment, we demonstrate that immunosuppression mimics the effects of growth factor activation, including tissue regeneration, neural precursor cell migration and functional recovery following ischemic injury. In the absence of growth factor treatment, mice with a functional immune system develop a prominent cavity in the cortex underlying the ischemic injury. In untreated immunodeficient NOD/SCID mice, however, the cortical cavity forms but is then filled with regenerated cortical tissue containing glial cells and subependyma derived neural stem and progenitor cells that migrate from their niche lining the lateral ventricles. The daily administration of Cyclosporine A also results in endogenous neural precursor cell migration and regenerated cortical tissue at the site of the cortical injury. Different from growth factor-treated animals is the finding that the regenerated cortical tissue in immunosuppressed animals is devoid of new neurons. Interestingly, both the growth factor and immunosuppressed (NOD/SCID and Cyclosporine A) treated animals displayed functional behavioural recovery despite the lack of neurogenesis within the regenerated cortical tissue. This article is part of a Special Issue entitled "Interaction between repair, disease, & inflammation."

Insulin signaling plays a dual role in Caenorhabditis elegans memory acquisition and memory retrieval.

Insulin signaling plays a prominent role in regulation of dauer formation and longevity in Caenorhabditis elegans. Here, we show that insulin signaling also is required in benzaldehyde-starvation associative plasticity, in which worms pre-exposed to the odor attractant benzaldehyde in the absence of food subsequently demonstrate a conditioned aversion response toward the odorant. Animals with mutations in insulin-related 1 (ins-1), abnormal dauer formation 2 (daf-2), and aging alteration 1 (age-1), which encode the homolog of human insulin, insulin/IGF-1 receptor, and PIP3 kinase, respectively, demonstrated significant deficits in benzaldehyde-starvation associative plasticity. Using a conditional allele, we show that the behavioral roles of DAF-2 signaling in associative plasticity can be dissociated, with DAF-2 signaling playing a more significant role in the memory retrieval than in memory acquisition. We propose DAF-2 signaling acts as a learning-specific starvation signal in the memory acquisition phase of benzaldehyde-starvation associative plasticity but functions to switch benzaldehyde-sensing amphid wing C neurons into an avoidance signaling mode during memory retrieval.