Impact of insulin signaling and proteasomal activity on physiological output of a neuronal circuit in aging Drosophila melanogaster.

Hrvoje Augustin,Kieran Mcgourty,Chi Tung Wong,Linda Partridge,Jennifer Adcott,Emmanuel Boucrot,Marcus J Allen

doi:10.1016/j.neurobiolaging.2018.02.027

Abstract

The insulin family of growth factors plays an important role in development and function of the nervous system. Reduced insulin and insulin-growth-factor signaling (IIS), however, can improve symptoms of neurodegenerative diseases in laboratory model organisms and protect against age-associated decline in neuronal function. Recently, we showed that chronic, moderately lowered IIS rescues age-related decline in neurotransmission through the Drosophila giant fiber escape response circuit. Here, we expand our initial findings by demonstrating that reduced functional output in the giant fiber system of aging flies can be prevented by increasing proteasomal activity within the circuit. Manipulations of IIS in neurons can also affect longevity, underscoring the relevance of the nervous system for aging.

Highlights

Aging neural circuits undergo morphological and functional changes that underlie different types of behavioral impairment (Hof and Morrison, 2004)
We have recently demonstrated a beneficial effect of reduced insulin-like growth factor signaling (IIS) on transmission through the escape response pathway of aging Drosophila melanogaster (Augustin et al, 2017)
First described in the squid ganglion (Young, 1936), the simple “Giant Fiber” circuits are a convenient system for studying neural development and function

Summary

Introduction

Aging neural circuits undergo morphological and functional changes that underlie different types of behavioral impairment (Hof and Morrison, 2004). Protective effects of impaired IIS have been reported in a number of species during normal aging and in models of neurodegenerative diseases (Cohen et al, 2006; Gontier et al, 2015; Tsuda et al, 2010). These seemingly contradictory findings define the so called “insulin paradox” (Cohen and Dillin, 2008; Steculorum et al, 2014)

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Conclusion