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Drosophila Neuronal Injury Follows a Temporal Sequence of Cellular Events Leading to Degeneration at the Neuromuscular Junction.

Lincoln BL, Alabsi SH, Frendo N, Freund R, Keller LC - J Exp Neurosci (2015)

Bottom Line: Our data provide insights into the early molecular events that occur during axonal and neuromuscular degeneration in a genetically tractable model organism.Importantly, the mechanisms that mediate neurodegeneration in flies are conserved in humans.Thus, these studies have implications for our understanding of the cellular and molecular events that occur in humans and will facilitate the identification of biomedically relevant targets for future treatments.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Quinnipiac University, Hamden, CT, USA.

ABSTRACT
Neurodegenerative diseases affect millions of people worldwide, and as the global population ages, there is a critical need to improve our understanding of the molecular and cellular mechanisms that drive neurodegeneration. At the molecular level, neurodegeneration involves the activation of complex signaling pathways that drive the active destruction of neurons and their intracellular components. Here, we use an in vivo motor neuron injury assay to acutely induce neurodegeneration in order to follow the temporal order of events that occur following injury in Drosophila melanogaster. We find that sites of injury can be rapidly identified based on structural defects to the neuronal cytoskeleton that result in disrupted axonal transport. Additionally, the neuromuscular junction accumulates ubiquitinated proteins prior to the neurodegenerative events, occurring at 24 hours post injury. Our data provide insights into the early molecular events that occur during axonal and neuromuscular degeneration in a genetically tractable model organism. Importantly, the mechanisms that mediate neurodegeneration in flies are conserved in humans. Thus, these studies have implications for our understanding of the cellular and molecular events that occur in humans and will facilitate the identification of biomedically relevant targets for future treatments.

No MeSH data available.


Related in: MedlinePlus

Mechanical injury of Drosophila larvae demonstrates damage to the majority of segmental peripheral nerves. (A) Fluorescently conjugated antibodies against HRP indicate intact segmental nerves in wild-type uninjured animals extending from the dorsal nerve cord down to their respective muscle targets. (B) After mechanical injury, HRP staining demonstrates ~8–12 damaged segmental nerves. The boxed region shows the location of the crush site. Scale bar = 100 μm.
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f1-jen-suppl.2-2015-001: Mechanical injury of Drosophila larvae demonstrates damage to the majority of segmental peripheral nerves. (A) Fluorescently conjugated antibodies against HRP indicate intact segmental nerves in wild-type uninjured animals extending from the dorsal nerve cord down to their respective muscle targets. (B) After mechanical injury, HRP staining demonstrates ~8–12 damaged segmental nerves. The boxed region shows the location of the crush site. Scale bar = 100 μm.

Mentions: In Drosophila, antibodies against HRP act as specific neuronal membrane markers allowing for visualization of all neurons, including peripheral motor neuron axons.24 In uninjured third instar larvae, fluorescently conjugated HRP antibodies were employed to visualize the series of paired segmental nerves exiting both sides of the ventral nerve cord and extending along the length of the animal. Our neuronal injury assay resulted in damage to ~6–12 segmental nerves depending on the precise location of the crush site, as indicated by a reduction in the amount of HRP staining immediately after injury (Fig. 1, boxed area). Sites of injury range from ~100 to 200 μm in length.


Drosophila Neuronal Injury Follows a Temporal Sequence of Cellular Events Leading to Degeneration at the Neuromuscular Junction.

Lincoln BL, Alabsi SH, Frendo N, Freund R, Keller LC - J Exp Neurosci (2015)

Mechanical injury of Drosophila larvae demonstrates damage to the majority of segmental peripheral nerves. (A) Fluorescently conjugated antibodies against HRP indicate intact segmental nerves in wild-type uninjured animals extending from the dorsal nerve cord down to their respective muscle targets. (B) After mechanical injury, HRP staining demonstrates ~8–12 damaged segmental nerves. The boxed region shows the location of the crush site. Scale bar = 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4612769&req=5

f1-jen-suppl.2-2015-001: Mechanical injury of Drosophila larvae demonstrates damage to the majority of segmental peripheral nerves. (A) Fluorescently conjugated antibodies against HRP indicate intact segmental nerves in wild-type uninjured animals extending from the dorsal nerve cord down to their respective muscle targets. (B) After mechanical injury, HRP staining demonstrates ~8–12 damaged segmental nerves. The boxed region shows the location of the crush site. Scale bar = 100 μm.
Mentions: In Drosophila, antibodies against HRP act as specific neuronal membrane markers allowing for visualization of all neurons, including peripheral motor neuron axons.24 In uninjured third instar larvae, fluorescently conjugated HRP antibodies were employed to visualize the series of paired segmental nerves exiting both sides of the ventral nerve cord and extending along the length of the animal. Our neuronal injury assay resulted in damage to ~6–12 segmental nerves depending on the precise location of the crush site, as indicated by a reduction in the amount of HRP staining immediately after injury (Fig. 1, boxed area). Sites of injury range from ~100 to 200 μm in length.

Bottom Line: Our data provide insights into the early molecular events that occur during axonal and neuromuscular degeneration in a genetically tractable model organism.Importantly, the mechanisms that mediate neurodegeneration in flies are conserved in humans.Thus, these studies have implications for our understanding of the cellular and molecular events that occur in humans and will facilitate the identification of biomedically relevant targets for future treatments.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Quinnipiac University, Hamden, CT, USA.

ABSTRACT
Neurodegenerative diseases affect millions of people worldwide, and as the global population ages, there is a critical need to improve our understanding of the molecular and cellular mechanisms that drive neurodegeneration. At the molecular level, neurodegeneration involves the activation of complex signaling pathways that drive the active destruction of neurons and their intracellular components. Here, we use an in vivo motor neuron injury assay to acutely induce neurodegeneration in order to follow the temporal order of events that occur following injury in Drosophila melanogaster. We find that sites of injury can be rapidly identified based on structural defects to the neuronal cytoskeleton that result in disrupted axonal transport. Additionally, the neuromuscular junction accumulates ubiquitinated proteins prior to the neurodegenerative events, occurring at 24 hours post injury. Our data provide insights into the early molecular events that occur during axonal and neuromuscular degeneration in a genetically tractable model organism. Importantly, the mechanisms that mediate neurodegeneration in flies are conserved in humans. Thus, these studies have implications for our understanding of the cellular and molecular events that occur in humans and will facilitate the identification of biomedically relevant targets for future treatments.

No MeSH data available.


Related in: MedlinePlus