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

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

doi:10.1038/s41598-021-89121-7

Cited by 17 publications

(30 citation statements)

References 103 publications

(71 reference statements)

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“…dTBI: Drosophila TBI model using a Piezoelectric actuator by Saikumar et al (2020) . HIFLI: Headfirst Impact FLy Injury model by Behnke et al (2021) .…”

Section: Drosophila Melanogaster As a Model For Studying Neu...mentioning

confidence: 99%

Drosophila melanogaster as a model to study age and sex differences in brain injury and neurodegeneration after mild head trauma

Behnke

Hardin

et al. 2023

Front. Neurosci.

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Repetitive physical insults to the head, including those that elicit mild traumatic brain injury (mTBI), are a known risk factor for a variety of neurodegenerative conditions including Alzheimer’s disease (AD), Parkinson’s disease (PD), and chronic traumatic encephalopathy (CTE). Although most individuals who sustain mTBI typically achieve a seemingly full recovery within a few weeks, a subset experience delayed-onset symptoms later in life. As most mTBI research has focused on the acute phase of injury, there is an incomplete understanding of mechanisms related to the late-life emergence of neurodegeneration after early exposure to mild head trauma. The recent adoption of Drosophila-based brain injury models provides several unique advantages over existing preclinical animal models, including a tractable framework amenable to high-throughput assays and short relative lifespan conducive to lifelong mechanistic investigation. The use of flies also provides an opportunity to investigate important risk factors associated with neurodegenerative conditions, specifically age and sex. In this review, we survey current literature that examines age and sex as contributing factors to head trauma-mediated neurodegeneration in humans and preclinical models, including mammalian and Drosophila models. We discuss similarities and disparities between human and fly in aging, sex differences, and pathophysiology. Finally, we highlight Drosophila as an effective tool for investigating mechanisms underlying head trauma-induced neurodegeneration and for identifying therapeutic targets for treatment and recovery.

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“…dTBI: Drosophila TBI model using a Piezoelectric actuator by Saikumar et al (2020) . HIFLI: Headfirst Impact FLy Injury model by Behnke et al (2021) .…”

Section: Drosophila Melanogaster As a Model For Studying Neu...mentioning

confidence: 99%

Drosophila melanogaster as a model to study age and sex differences in brain injury and neurodegeneration after mild head trauma

Behnke

Hardin

et al. 2023

Front. Neurosci.

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“…Vacuolization is also seen following head trauma exposure ( Saikumar, Byrns et al. 2020 , Behnke, Ye et al. 2021 ).…”

Section: Before You Beginmentioning

confidence: 99%

“…This strategy incorporates existing standard fly fixation, dissection and whole-brain staining techniques combined with advanced microscopy (confocal or two-photon) which can be used with any wild-type or transgenic fly lines. Validation of this method demonstrates that it can be used to discriminate neurodegeneration found in models of aging and tauopathy ( Figure 2 ), and neurodegeneration secondary to head trauma ( Behnke, Ye et al. 2021 ).…”

Section: Expected Outcomesmentioning

confidence: 99%

“…This approach preserves the whole-brain architecture and enables rapid, reproducible, and quantitative analyses of vacuole-like degeneration associated with specific brain regions. For complete details on the use and execution of this protocol, please refer to Behnke et al. (2021) .…”

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confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Behnke et al. (2021) .…”

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confidence: 99%

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A protocol to detect neurodegeneration in Drosophila melanogaster whole-brain mounts using advanced microscopy

Behnke¹,

Ye²,

Moberg³

et al. 2021

STAR Protocols

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Summary Drosophila melanogaster is an excellent model organism to study neurodegeneration. Assessing evident neurodegeneration within the fly brain involves the laborious preparation of thin-sectioned H&E-stained heads to visualize brain vacuole degeneration. Here, we present an advanced microscopy-based protocol, without the need for sectioning, to detect vacuole degeneration within whole fly brains by applying commonly used stains to reveal the brain parenchyma. This approach preserves the whole-brain architecture and enables rapid, reproducible, and quantitative analyses of vacuole-like degeneration associated with specific brain regions. For complete details on the use and execution of this protocol, please refer to Behnke et al. (2021) .

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dTBI2: A Calibrated, Tunable Device for Administering Traumatic Brain Injury in Drosophila

Ratner,

Fetchko,

Mathivanan

et al. 2024

Current Protocols

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The second‐generation Drosophila traumatic brain injury (TBI) device dTBI2 improves Drosophila TBI administration by providing a moderate‐throughput, tunable, head‐specific injury. Our updated device design improves user‐friendliness, eliminates inconsistencies in injury timing, and has an updated circuit design to extend the longevity of delicate electronic components. dTBI2 improves reproducibility across users and runs, and results in more consistent post‐injury phenotypes. This protocol describes the construction, calibration, and use of the dTBI2 device, which uses an Arduino‐controlled piezoelectric actuator to deliver a force that compresses a fly head against a metal collar. The duration and depth of head compression is tunable, allowing calibration of injury severity. All device components are commercially available, and the entire device can be constructed in under a week for less than $1000. The dTBI2 design will enable any lab to build a highly reliable, low‐cost device for Drosophila TBI, facilitating increased adoption and ease of exploration of closed‐head TBI in Drosophila for forward genetic screens. We describe below the three protocols necessary for constructing a dTBI2 device. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: Construction of the dTBI2 control deviceBasic Protocol 2: Construction of the piezoelectric actuator housingBasic Protocol 3: Administration of dTBI2 injuries

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

Cited by 17 publications

References 103 publications

Drosophila melanogaster as a model to study age and sex differences in brain injury and neurodegeneration after mild head trauma

Drosophila melanogaster as a model to study age and sex differences in brain injury and neurodegeneration after mild head trauma

A protocol to detect neurodegeneration in Drosophila melanogaster whole-brain mounts using advanced microscopy

dTBI2: A Calibrated, Tunable Device for Administering Traumatic Brain Injury in Drosophila

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