Nervous system injury or nervous system disease have broad effects on the functional connectivity of the whole nervous system, but how injury signals spread across the neural circuits remains undefined. Experiments were conducted which show that within hours after injury, suppression of axon transport in all axons, whether injured or not, has decreased mechano- and chemosensory signal transduction in uninjured bystander neurons. Within the span of the spinal cord called the dorsal horn – the electrical signals get transmitted from one neuron to another neuron across the synapses by means of chemical messengers (neurotransmitters). Signals then move up the spinal cord to the brain. Injury/disease that affects a relatively small number of brain cells causes a chain reaction that inhibits/stops activity across a vast network of neural circuit connections, as per new research. The study helped explain why people can suffer from temporary but severe losses in cognitive function in traumatic brain injury cases.
What is Bystander Effect?
Bystander effect is the induction of the biological effects in cells that are indirectly traversed by a charged particle. The effects can be seen in cells, tissues, or organisms that receive some type of signals from irradiated cells, tissues, or organisms. Bystander study implies – that the target for the biological effects of radiation is much larger than the cell, which could make a simple linear extrapolation of radiation risks from high to low doses of questionable validity. Bystander effects have been invoked to explain the onset of autoimmune responses – as self-antigens can be present at the site of the immune response elicited by foreign antigen.
Research on the fruit fly Drosophila – which is a well-established model for neural networks in people, demonstrated that relatively minimal injury to a small number of axons in a larger bundle rippled out beyond the severed axons. This suppressed the sensory signals among neurons that were not directly damaged. Even the bystander neurons that are not injured or diseased can sense that there is an injury and can radically change their function. This study describes why traumatic brain injury or disease results in temporary but severe loss of cognitive function. When there is any injury in the nervous system – it is not just the broken neurons that are affected; it is maybe all of the neurons that become affected.
Bystander phenomena might not have a precise role in the effector phase of the immune response and may reflect the existence of a network of connections between the different cellular elements of the immune system.
1. Partial nerve injury broadly suppresses neurophysiology, even in uninjured bystander neurons.
2. Cac/dSarm/MAPK signaling is required in bystander neurons to suppress neurophysiology.
3. dSarm NADase activity is required for axon degeneration but not bystander effects.
4. Glia spread injury signals to suppress bystander neurons through Draper signaling.
Mechanism
When there is any kind of injury, the brain cells cause a chain reaction that stops or inhibits the damaging activity across a vast network of neural connections. This mechanism helps the brain conserve large amounts of energy following a disease or injury, which gets restored after the injury clears. However, research reveals that a small injury can cause the whole nervous system to shut down. From an evolutionary point, Freeman theorizes that the “bystander” effect may help to conserve energy in the large area of the nervous system following disease or injury. Bystander neurons that effectively revive once it becomes clear from the injured state. Scientists say that it allows the nervous system to pause after any injury and enables cells to assess their condition and, if they are not healthy, it activates programs to destroy themselves.
Unexpectedly, researchers found the axon death molecule – dSarm, but not its NAD+ hydrolase activity, was required cell-autonomously for these early changes in neuronal cell biology in bystander neurons. As were the voltage-gated calcium channel Cacophony (Cac) and the mitogen-activated protein kinase (MAPK) signaling cascade. Bystander neurons functionally recovered at later time points, while severed axons degenerated via α/Armadillo/Toll-interleukin receptor homology domain (dSarm)/Axundead signaling, and independently of Cac/MAPK. Interestingly, suppression of bystander neuron function required Draper/MEGF10 signaling in glia, indicating glial cells spread injury signals and actively suppress bystander neuron function.