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Written | Edited by xiao xia | Typesetting by Wang Duoyu | Hydrographic stroke, Alzheimer's disease, Parkinson's disease, and Huntington's disease can cause a large number of neuron loss and gliosis, which affects vision and motor function
.
Neurons do not regenerate on their own, and the brain can sometimes reshape its neural circuits, enough to restore some visual functions after a stroke, but this process is very slow
.
If the regeneration of neurons can be induced in the body, it will undoubtedly bring a substantial breakthrough in the treatment of these major diseases
.
Stem cell therapy is regarded as a promising strategy, but it has not yet been able to solve transplant rejection and tumorigenicity of transplanted cells
.
A series of studies by Professor Chen Gong of Jinan University and others have shown that the endogenous astrocytes of the brain can be directly converted into neurons by expressing the transcription factor NeuroD1
.
However, it is not clear whether these reprogrammed neurons undergo normal development, whether they are integrated into existing neural circuits, and whether they have acquired the unique functional characteristics of this circuit
.
Recently, researchers from Purdue University in the United States published a research paper titled Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy in Frontiers in Cell and Developmental Biology
.
The study used a mouse model of cerebral ischemia to study the effect of gene therapy on visual cortical circuit integration and functional recovery.
It was found that NeuroD1 reprogrammed new neurons integrated into the cortical circuit and obtained direct visual function, helping the brain to heal itself.
.
In addition, reprogrammed neurons exhibited directional selectivity and maturity in functional connectivity
.
Therefore, NeuroD1 therapy opens up a new way to restore vision and motor function after stroke
.
In order to prove the effect of direct reprogramming in vivo on visual function after cortical ischemic injury, the research team injected mice with endothelin 1, which causes neuron loss and glial scar formation
.
After scarring, they used adeno-associated virus (AAV9) to transfect the Cre-dependent reprogramming gene NeuroD1 together with the Cre recombinase gene under the GFAP promoter to glial cells
.
The results showed that the reprogrammed new neurons gradually expressed neuronal markers and gradually lost glial cell markers
.
Next, the research team performed immunostaining on cortical neuron markers Tbr1, superficial marker Cux1, and deep marker Ctip2 to verify whether reprogrammed neurons acquired the identity of cortical neurons and whether they formed a layered structure
.
At 3 and 6 weeks after virus injection, more than 50% of reprogrammed neuronal cells expressed Tbr1, indicating the characteristics of cortical neurons
.
The superficial and deep reprogrammed neurons were immunopositive for Cux1 and Ctip2, respectively
.
These results indicate that NeuroD1 effectively converts glial cells into neurons, and neurons acquire the identity of cortical neurons and form cortical layered structures, thereby achieving functional circuit integration
.
In order to evaluate the functional recovery of the primary visual cortex after reprogramming, the research team used extracellular recording technology to record visual evoked potentials (VEPs) in awake mice
.
After cerebral ischemic injury, compared with the transfected control virus, the VEP amplitude of the hemisphere of Neuron D1 transfected mice was significantly increased
.
In addition to synchronized group activity, they also examined the visual responses of individual neurons and found that the hemispheres of mice transfected with NeuroD1 showed higher peak discharges
.
These results indicate that direct reprogramming in vivo can restore visual response
.
Optogenetic-assisted loop map analysis technology (CRACM) can measure the long-range projection of specific gene markers and the strength of cell-to-cell connections
.
In order to directly measure the circuit connectivity of reprogrammed neurons, the research team used CRACM technology in isolated acute brain slices
.
The results showed that reprogrammed neurons showed strong light-induced excitatory postsynaptic current (EPSC), and neighboring neurons also received considerable excitatory input
.
In addition, the reprogrammed neurons acquire directional and direction-selective responses over time, indicating that their functions are integrated into local visual cortical circuits
.
In summary, this work proves that NeuroD1 directly reprograms glial cells into neurons and promotes the integration of their neural circuits, leading to the restoration of visual function after ischemic injury
.
Therefore, the in vivo direct reprogramming technology based on NeuroD1 is a promising new gene therapy to repair brain damage
.
It is reported that this work was completed by Alexander A.
Chubykin's team at Purdue University.
Professor Chen Gong's team provided plasmid and technical guidance for this work, as well as some auxiliary experiments
.
This work also clarified the research controversy about NeuroD1-mediated transdifferentiation of glial cells into neurons to a certain extent
.
Related reading: Professor Chen Gong's interpretation of the research controversy on the transdifferentiation of glial cells into neurons.
Links to the paper: https:// open for reprinting, welcome to forward to Moments and WeChat groups
.
Neurons do not regenerate on their own, and the brain can sometimes reshape its neural circuits, enough to restore some visual functions after a stroke, but this process is very slow
.
If the regeneration of neurons can be induced in the body, it will undoubtedly bring a substantial breakthrough in the treatment of these major diseases
.
Stem cell therapy is regarded as a promising strategy, but it has not yet been able to solve transplant rejection and tumorigenicity of transplanted cells
.
A series of studies by Professor Chen Gong of Jinan University and others have shown that the endogenous astrocytes of the brain can be directly converted into neurons by expressing the transcription factor NeuroD1
.
However, it is not clear whether these reprogrammed neurons undergo normal development, whether they are integrated into existing neural circuits, and whether they have acquired the unique functional characteristics of this circuit
.
Recently, researchers from Purdue University in the United States published a research paper titled Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy in Frontiers in Cell and Developmental Biology
.
The study used a mouse model of cerebral ischemia to study the effect of gene therapy on visual cortical circuit integration and functional recovery.
It was found that NeuroD1 reprogrammed new neurons integrated into the cortical circuit and obtained direct visual function, helping the brain to heal itself.
.
In addition, reprogrammed neurons exhibited directional selectivity and maturity in functional connectivity
.
Therefore, NeuroD1 therapy opens up a new way to restore vision and motor function after stroke
.
In order to prove the effect of direct reprogramming in vivo on visual function after cortical ischemic injury, the research team injected mice with endothelin 1, which causes neuron loss and glial scar formation
.
After scarring, they used adeno-associated virus (AAV9) to transfect the Cre-dependent reprogramming gene NeuroD1 together with the Cre recombinase gene under the GFAP promoter to glial cells
.
The results showed that the reprogrammed new neurons gradually expressed neuronal markers and gradually lost glial cell markers
.
Next, the research team performed immunostaining on cortical neuron markers Tbr1, superficial marker Cux1, and deep marker Ctip2 to verify whether reprogrammed neurons acquired the identity of cortical neurons and whether they formed a layered structure
.
At 3 and 6 weeks after virus injection, more than 50% of reprogrammed neuronal cells expressed Tbr1, indicating the characteristics of cortical neurons
.
The superficial and deep reprogrammed neurons were immunopositive for Cux1 and Ctip2, respectively
.
These results indicate that NeuroD1 effectively converts glial cells into neurons, and neurons acquire the identity of cortical neurons and form cortical layered structures, thereby achieving functional circuit integration
.
In order to evaluate the functional recovery of the primary visual cortex after reprogramming, the research team used extracellular recording technology to record visual evoked potentials (VEPs) in awake mice
.
After cerebral ischemic injury, compared with the transfected control virus, the VEP amplitude of the hemisphere of Neuron D1 transfected mice was significantly increased
.
In addition to synchronized group activity, they also examined the visual responses of individual neurons and found that the hemispheres of mice transfected with NeuroD1 showed higher peak discharges
.
These results indicate that direct reprogramming in vivo can restore visual response
.
Optogenetic-assisted loop map analysis technology (CRACM) can measure the long-range projection of specific gene markers and the strength of cell-to-cell connections
.
In order to directly measure the circuit connectivity of reprogrammed neurons, the research team used CRACM technology in isolated acute brain slices
.
The results showed that reprogrammed neurons showed strong light-induced excitatory postsynaptic current (EPSC), and neighboring neurons also received considerable excitatory input
.
In addition, the reprogrammed neurons acquire directional and direction-selective responses over time, indicating that their functions are integrated into local visual cortical circuits
.
In summary, this work proves that NeuroD1 directly reprograms glial cells into neurons and promotes the integration of their neural circuits, leading to the restoration of visual function after ischemic injury
.
Therefore, the in vivo direct reprogramming technology based on NeuroD1 is a promising new gene therapy to repair brain damage
.
It is reported that this work was completed by Alexander A.
Chubykin's team at Purdue University.
Professor Chen Gong's team provided plasmid and technical guidance for this work, as well as some auxiliary experiments
.
This work also clarified the research controversy about NeuroD1-mediated transdifferentiation of glial cells into neurons to a certain extent
.
Related reading: Professor Chen Gong's interpretation of the research controversy on the transdifferentiation of glial cells into neurons.
Links to the paper: https:// open for reprinting, welcome to forward to Moments and WeChat groups
