Repetitive mild head trauma induces activity mediated lifelong brain deficits in a novel Drosophila model

Joseph A Behnke,Changtian Ye,James Q Zheng,Aayush Setty,Kenneth H Moberg

doi:10.1038/s41598-021-89121-7

Abstract

Mild head trauma, including concussion, can lead to chronic brain dysfunction and degeneration but the underlying mechanisms remain poorly understood. Here, we developed a novel head impact system to investigate the long-term effects of mild head trauma on brain structure and function, as well as the underlying mechanisms in Drosophila melanogaster. We find that Drosophila subjected to repetitive head impacts develop long-term deficits, including impaired startle-induced climbing, progressive brain degeneration, and shortened lifespan, all of which are substantially exacerbated in female flies. Interestingly, head impacts elicit an elevation in neuronal activity and its acute suppression abrogates the detrimental effects in female flies. Together, our findings validate Drosophila as a suitable model system for investigating the long-term effects of mild head trauma, suggest an increased vulnerability to brain injury in female flies, and indicate that early altered neuronal excitability may be a key mechanism linking mild brain trauma to chronic degeneration.

Highlights

Mild head trauma, including concussion, can lead to chronic brain dysfunction and degeneration but the underlying mechanisms remain poorly understood
Multiple flies (10–15 flies at a time) are contained within a custom plastic injury vial designed to fit within our injury rig consisting of a cradle that is connected to a pulley system with a specific counterweight
The light tamping is employed for two purposes: (1) to cause all the flies to fall to the bottom so they will travel the same distance before the head impact for consistent impact speed and (2) to allow the flies to orientate in a head-upward posture as part of their startle-induced negative geotactic climbing response

Summary

Introduction

Mild head trauma, including concussion, can lead to chronic brain dysfunction and degeneration but the underlying mechanisms remain poorly understood. Repetitive head trauma, including mild injuries such as concussion, is a risk factor for developing several neurodegenerative disorders, including Alzheimer’s disease (AD)[1,2], Parkinson’s disease (PD)[3], Amyotrophic lateral sclerosis (ALS)[4] and chronic traumatic encephalopathy (CTE)[5,6,7,8,9] Each of these conditions arise from distinct etiologies, they share some common features including abnormal protein d eposits[3,4,10,11], impaired axonal transport12, swelling[13] and r etraction[14], immune cell activation, and e xcitotoxicity[15,16,17,18,19,20,21,22], which result in progressive cellular degeneration, cell death, and frank brain atrophy. Head-specific impact models have recently been developed in which physical head impacts were delivered to the heads of individually restrained flies[46,47,48], but no long-term study was carried out to examine the detrimental effects that might develop later in life

Methods

Results

Discussion

Conclusion