Citation
Evaluating Aav Tropism For Neonatal Mouse Cerebellum

Material Information

Title:
Evaluating Aav Tropism For Neonatal Mouse Cerebellum
Series Title:
19th Annual Undergraduate Research Symposium
Creator:
Gil, Raquel
Language:
English
Physical Description:
Undetermined

Subjects

Subjects / Keywords:
Center for Undergraduate Research
Center for Undergraduate Research
Genre:
Conference papers and proceedings
Poster

Notes

Abstract:
The cerebellum is a vital area of the brain that receives sensory information and helps regulate motor movements such as posture, balance, coordination, and speech. More recently the cerebellum was discovered to play a role in emotion as well. Damage to the cerebellum and loss of some of these functions can occur as a result of neurodegenerative disorders, such as Alzheimer’s Disease. Problems with coordination that occur in later stages of Alzheimer’s have been linked to amyloid plaque build-up in areas of the brain, including the cerebellum. Adeno-associated virus (AAV) has the potential to be a successful gene therapy for Alzheimer’s disease as well as many other neurodegenerative disorders. AAV is a non-pathogenic virus that has been used as a tool in gene therapy and in creating isogenic human disease models. Recombinant AAV (rAAV) is used for gene delivery because it can target specific tissue types through rAAV transduction. There are different serotypes of AAV that may have different efficacies in different areas of the brain. The purpose of this study was to compare AAV1, AAV5, AAV6, and AAV8 and evaluate each AAV serotype tropism in the cerebellum. ( en )
General Note:
Research authors: Raquel Gil, Pedro E. Cruz, Sanjana Bhargava, Amanda Hernandez, Sana Mahmood, Catalina Mejia, Kimberly Menezes, Odinaka Osigwe, Ramona Parkash, Neal Patel, Gia Paterno, Abraham Quader, Ankitha Reddy, Lauren Rostkowsi, Georgia Soares, Dan Tran, Trung Van, and Todd E. Golde - University of Florida
General Note:
Faculty Mentor: The cerebellum is a vital area of the brain that receives sensory information and helps regulate motor movements such as posture, balance, coordination, and speech. More recently the cerebellum was discovered to play a role in emotion as well. Damage to the cerebellum and loss of some of these functions can occur as a result of neurodegenerative disorders, such as Alzheimer’s Disease. Problems with coordination that occur in later stages of Alzheimer’s have been linked to amyloid plaque build-up in areas of the brain, including the cerebellum. Adeno-associated virus (AAV) has the potential to be a successful gene therapy for Alzheimer’s disease as well as many other neurodegenerative disorders. AAV is a non-pathogenic virus that has been used as a tool in gene therapy and in creating isogenic human disease models. Recombinant AAV (rAAV) is used for gene delivery because it can target specific tissue types through rAAV transduction. There are different serotypes of AAV that may have different efficacies in different areas of the brain. The purpose of this study was to compare AAV1, AAV5, AAV6, and AAV8 and evaluate each AAV serotype tropism in the cerebellum. - Center for Undergraduate Research,

Record Information

Source Institution:
University of Florida
Rights Management:
Copyright Raquel Gil. Permission granted to University of Florida to digitize and display this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder.

Downloads

This item is only available as the following downloads:


Full Text

PAGE 1

Evaluating AAV Tropism for Neonatal Mouse Cerebellum Raquel Gil, Awilda Rosario, Pedro E Cruz, Abraham Quader Sanjana Bhargava, Amanda Hernandez, Sana Mahmood, Catalina Mejia, Kimberly Menezes, Odinaka Osigwe Ramona Parkash, Neal Patel, Gia Paterno, Ankitha Reddy, Lauren Rostkowski Georgia Soares, Dan Tran, Trung Van, Carolina Ceballos, Xuefei Liu and Todd E Golde McKnight Brain Institute, Department of Neuroscience, University of Florida, Gainesville, FL Methodology Introduction Strongest AAV Expression Acknowledgements Other AAV Expression disease is a neurodegenerative disease that causes dementia. The level of these symptoms increase over time, and eventually interfere with amyloid plaques, which are protein fragments that end up damaging and killing nerve cells when they are built up.. The cause unknown and, at the moment, there is no cure either. Research that focuses on the areas of the brain that are affected by these beta amyloid plaques may help shed light on the cause brain that plays a role in motor control and cognitive functions. As previously Therefore, learning what can be used to treat the beta amyloid plaques in this Capsid serotypes 1 5 6 and 8 were evaluated through a microscope at 4 X, 10 X, and 20 X rAAV vectors were utilized which encoded an EGFP protein driven by a CBA promoter Vectors were then sent towards the cerebellum of the mouse Analysis of the pictures were based on the brown color ; a stronger and more apparent brown color means a stronger expression of the AAV in the cerebellum Todd E. Golde Provided me the opportunity to complete this research project in his laboratory. Pedro E. Cruz Strong mentor that taught me laboratory techniques that were used throughout this research project. Aim The aim of this study was to evaluate the level of expression of multiple Adeno associated viruses (AAV) on the cerebellum in neonatal mice The results of this study would provide insight into targeting cerebellum that have been adversely affected by disease Future Work Using AAV 8 to successfully transduce proteins into the cerebellum may help in repairing cells in this area for those with and other neurodegenerative disorders with symptoms in the cerebellum The ability to regenerate and repair of the nerve cells that have been damaged in the cerebellum could possibly serve as a form of treatment for those with disease AAV1 Abstract The cerebellum is a vital area of the brain that receives sensory information and helps regulate motor movements such as posture, balance, coordination, and speech. More recently the cerebellum was discovered to play a role in emotion as well. Damage to the cerebellum and loss of some of these functions can occur as a result of up in areas of the brain, including the cerebellum. Adeno associated virus (AAV) has the neurodegenerative disorders. AAV is a non pathogenic virus that has been used as a tool in gene therapy and in creating isogenic human disease models. Recombinant AAV ( rAAV ) is used for gene delivery because it can target specific tissue types through rAAV transduction. There are different serotypes of AAV that may have different efficacies in different areas of the brain. The purpose of this study was to compare AAV1, AAV5, AAV6, and AAV8 and evaluate each AAV serotype tropism in the cerebellum. AAV5 AAV5 AAV6 AAV6 AAV8 AAV8 AAV1 AAV1 AAV5 AAV5 AAV6 AAV6 AAV8 AAV8 AAV1 AAV5 AAV6 AAV8 A B C D Conclusion AAV 8 demonstrated the strongest expression through viral cells because there was a large amount of in all three of the pictures taken and shown in the previous section AAV 1 and AAV 5 provided the weakest form of expression because there was almost no in any of the mice cerebellum AAV 6 had a few areas of especially in mouse 2 however, it was still a significantly weaker expression than that of AAV 8 Overall the most optimal vector for successfully reaching the cerebellum was AAV 8 therefore, it is the most effective method of protein transduction out of the 4 AAVs used in this study Mouse 1 Mouse 2 Mouse 3 AAV8 AAV1 AAV1 AAV1 Mouse 1 Mouse 2 Mouse 3 AAV6 AAV6 AAV6 Mouse 1 Mouse 2 Mouse 3 AAV5 AAV5 Mouse 1 Mouse 2 Surgical Procedure