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| Neuroregeneration |
What would happen to our bodies if cells that are damaged
never repair themselves? Unfortunately,
our body structures would eventually break down and no longer function
correctly. Luckily, with vast research
conducted, there is a solution! Neuroregeneration, the regrowth or repair
of neural tissues, is imperative to maintaining functions within a system. By repairing or replacing damaged cells, the
damaged area has hopes of gaining back normal functioning. The regeneration of neural cells has proven
to be critical in helping patients with spinal cord injury. Researchers hope to also find cures to
neurodegenerative diseases such as Alzheimer’s and Parkinson’s using
neuroregeneration.
Jacob Nordman is
a Ph.D. candidate working in the Kabbani Lab of the Krasnow Institute at George Mason University. He has done extensive research on α7 nAChR and
Gprin1 interactions and how they regulate axon and growth cone development, navigation,
and regeneration. He presented his research
on α7 nAChR and Gprin1 interactions within hippocampal neurons.
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| α7 nAChR Along with Gprin 1 Contribute to Axonal Growth |
Growth cones, which contain F-actin and microtubules, are situated on
axons and dendrites. They are crucial in
guiding axonal development, which allows for the precise wiring of neural circuitry. To help you picture what a growth cone is,
imagine it as an arm and a hand. There
are three layers to a growth cone: central zone (forearm), transitional zone
(palm), and peripheral zone (arm used to pull a growth cone to its
destination). Growth cones work with
gradients, where a guidance cue can result in either growth or retraction. The process during which growth cones guide
axonal development has seven states: initiation,
formation, guidance, branching, turning, arrest, and retraction.
The α7 nAChR
receptor is a ligand gated calcium channel which has a high affinity for
nicotine and ACh, and has been linked to illnesses such as schizophrenia and
Alzheimer’s due to its high expression in the hippocampus. Although there have been studies emphasizing
the contribution of α7 nAChR to neuroregeneration, the mechanisms behind this
process have not been fully understood. Gprin1 (G protein regulated inducer of
neurite outgrowth 1) is a membrane-bound protein that is highly enriched in
growth cones. Nordman’s research focuses
on how α7 nAChR along with Gprin 1 contribute to axonal growth and navigation
in hippocampal development.
Using fluorescent
markers to detect proteins and their antibodies within hippocampal brain
slices indicated that α7 nAChR and Gprin 1 had the highest expressions during
early development at the soma and growth cones, where the cytoskeletal growth
demands are highest. During the early
stages of development, neurons are still migrating to their final destinations
and are highly dependent on growth cones to guide the paths. To confirm strong and high overlap of α7 nAChR
and Gprin 1 in the soma and growth cones,
transfection was used to insert α7 nAChR into Neuro-2a cells, which are neuron-like cells that produce only Gprin
1. Afterwards, to observe the
interactions between the two proteins, immunoprecipitation was used to remove Gprin 1 from the Neuro-2a
cells, in order to isolate α7 nAChR.
Upon removing Gprin 1 with siRNA,
the direct interaction between α7 nAChR and Gprin 1 weakened, confirming not
just the presence of both α7 nAChR and Gprin 1 in the soma and growth cone, but
also that there is an active and direct interaction between the two.
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| Immunoprecipitation Process |
Another experiment on the relationship between α7 nAChR and
Gprin 1 was done and it was found the Gprin 1 is a master switch for α7 nAChR. When there was more Gprin 1, there was an
increased growth in axons, more branching, as well as a higer surface area of
the growth cones. Conversely, when there
was less Gprin 1, the growth cones retracted and shrinkage was seen. These results pointed out that whatever is done to Gprin 1 offsets what happens to α7 nAChR.
The research done by Nordman suggests that α7 nAChR and
Gprin 1 together play a critical role in axonal development in the hippocampus. This study furthers the field of
neuroregeneration and can be used to develop drugs to repair neural damage by
having more effective ways to regenerate axons and quickly guide them to their
destinations. The overactivation of α7 receptors
has been cited in Alzheimer’s disease, causing axons to retract and neural cells
to die. Targeting α7 receptors with
antagonists would surely result in useful treatments for Alzheimer’s or other
neurodegenerative illnesses. Myelination
is the formation of a layer called the myelin sheath around the axons of
neurons. Myelin increases the speed of
impulses through the axon and stabilizes it, which inhibits the regeneration of
axons and branching of growth cones.
Thus, inhibiting myelin promotes movement within growth cones. Inhibiting myelination increases regeneration
of axons which is needed to treat neurodegenerative illnesses. However, can this sort of treatment be a
double-edged sword? This may cause
damage to myelin, which contributes to multiple sclerosis. Neurotrophins
are a class of growth factors which contribute to the survival and development of
neurons. Possibly with more studies done
on neurotrophins and their interactions with myelin, more safe and effective treatments
can be created to treat neurodegenerative illnesses.
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