Uncovering the role of growth cones in migrating neurons for promoting neuronal migration and regeneration in the injured brain - a breakthrough by Nagoya City University.
In a groundbreaking discovery, a research group led by Kazunobu Sawamoto at Nagoya City University and National Institute for Physiological Sciences, along with scientists Chikako Nakajima and Masato Sawada, has revealed the presence of a growth cone at the tip of migrating neurons. This growth cone, much like axonal growth cones, plays a crucial role in regulating neuronal migration by interacting with the extracellular environment. Their findings shed light on how this growth cone, specifically expressing PTPσ, senses the extracellular matrix and facilitates neuronal migration in the injured brain, ultimately leading to functional recovery.
The study focused on unraveling the function of this growth cone-like structure in mouse brain neurons. By utilizing super-resolution microscopy, the researchers delved into the cytoskeletal dynamics and molecular characteristics of the neuronal tip. They discovered that the growth cone responds to external signals through PTPσ, guiding the directionality of migration and initiating the movement of the cell body. Furthermore, the growth cone's response to chondroitin sulfate (CS) through PTPσ influences neuronal migration; when exposed to CS, the growth cones collapse, inhibiting migration, but can revert to an extended state when interacting with heparan sulfate (HS), thus promoting migration.
To explore the potential of promoting neuronal migration in the injured brain, the researchers applied HS-containing biomaterial to CS-rich injured sites. They utilized HS-containing gelatin-fiber nonwoven fabric as a structural scaffold for migrating neurons, demonstrating that the applied fibers aided in the extension of growth cones and promoted neuronal migration in the injured brain. Additionally, implantation of the HS-enriched gelatin fabric led to the regeneration of mature neurons and restoration of neurological functions, hinting at the development of innovative regeneration technologies based on enhancing neuronal migration through growth cone-mediated interactions with the extracellular environment.
Considering that aging alters the physical properties of the brain extracellular matrix, including CSPG, the researchers emphasized the need to investigate whether growth cone-mediated treatment could also be effective in recruiting new neurons in aged brains. This study opens up new possibilities for leveraging growth cones to attract new neurons to damaged sites in the brain, potentially offering a novel approach for regeneration in both injured and aged brains.
The full details of this pioneering research can be found in the article titled "Identification of the growth cone as a probe and driver of neuronal migration in the injured brain," published in Nature Communications. This study marks a significant advancement in our understanding of neuronal migration and regeneration processes in the brain after injury.
Source: https://www.eurekalert.org/news-releases/1036862
The study focused on unraveling the function of this growth cone-like structure in mouse brain neurons. By utilizing super-resolution microscopy, the researchers delved into the cytoskeletal dynamics and molecular characteristics of the neuronal tip. They discovered that the growth cone responds to external signals through PTPσ, guiding the directionality of migration and initiating the movement of the cell body. Furthermore, the growth cone's response to chondroitin sulfate (CS) through PTPσ influences neuronal migration; when exposed to CS, the growth cones collapse, inhibiting migration, but can revert to an extended state when interacting with heparan sulfate (HS), thus promoting migration.
To explore the potential of promoting neuronal migration in the injured brain, the researchers applied HS-containing biomaterial to CS-rich injured sites. They utilized HS-containing gelatin-fiber nonwoven fabric as a structural scaffold for migrating neurons, demonstrating that the applied fibers aided in the extension of growth cones and promoted neuronal migration in the injured brain. Additionally, implantation of the HS-enriched gelatin fabric led to the regeneration of mature neurons and restoration of neurological functions, hinting at the development of innovative regeneration technologies based on enhancing neuronal migration through growth cone-mediated interactions with the extracellular environment.
Considering that aging alters the physical properties of the brain extracellular matrix, including CSPG, the researchers emphasized the need to investigate whether growth cone-mediated treatment could also be effective in recruiting new neurons in aged brains. This study opens up new possibilities for leveraging growth cones to attract new neurons to damaged sites in the brain, potentially offering a novel approach for regeneration in both injured and aged brains.
The full details of this pioneering research can be found in the article titled "Identification of the growth cone as a probe and driver of neuronal migration in the injured brain," published in Nature Communications. This study marks a significant advancement in our understanding of neuronal migration and regeneration processes in the brain after injury.
Source: https://www.eurekalert.org/news-releases/1036862
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