Genetic dissection of the neuro-glio-vascular machinery in the adult brain
Abstract The adult brain actively controls its metabolic homeostasis via the circulatory system at the blood brain barrier interface. The mechanisms underlying the functional coupling from neuron to vessel remain poorly understood. Here, we established a novel method to genetically isolate the indiv...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-01-01
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| Series: | Molecular Brain |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13041-017-0345-4 |
| _version_ | 1818385780858421248 |
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| author | Gregory W. Kirschen Rachel Kéry Hanxiao Liu Afrinash Ahamad Liang Chen Wendy Akmentin Ramya Kumar Joel Levine Qiaojie Xiong Shaoyu Ge |
| author_facet | Gregory W. Kirschen Rachel Kéry Hanxiao Liu Afrinash Ahamad Liang Chen Wendy Akmentin Ramya Kumar Joel Levine Qiaojie Xiong Shaoyu Ge |
| author_sort | Gregory W. Kirschen |
| collection | DOAJ |
| description | Abstract The adult brain actively controls its metabolic homeostasis via the circulatory system at the blood brain barrier interface. The mechanisms underlying the functional coupling from neuron to vessel remain poorly understood. Here, we established a novel method to genetically isolate the individual components of this coupling machinery using a combination of viral vectors. We first discovered a surprising non-uniformity of the glio-vascular structure in different brain regions. We carried out a viral injection screen and found that intravenous Canine Adenovirus 2 (CAV2) preferentially targeted perivascular astrocytes throughout the adult brain, with sparing of the hippocampal hilus from infection. Using this new intravenous method to target astrocytes, we selectively ablated these cells and observed severe defects in hippocampus-dependent contextual memory and the metabolically regulated process of hippocampal neurogenesis. Combined with AAV9 targeting of neurons and endothelial cells, all components of the neuro-glio-vascular machinery can be simultaneously labeled for genetic manipulation. Together, we demonstrate a novel method, which we term CATNAP (CAV/AAV Targeting of Neurons and Astrocytes Perivascularly), to target and manipulate the neuro-glio-vascular machinery in the adult brain. |
| first_indexed | 2024-12-14T03:43:36Z |
| format | Article |
| id | doaj.art-0e8964114aca41bcb3f1a43c4fb128e3 |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-14T03:43:36Z |
| publishDate | 2018-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-0e8964114aca41bcb3f1a43c4fb128e32022-12-21T23:18:24ZengBMCMolecular Brain1756-66062018-01-0111111510.1186/s13041-017-0345-4Genetic dissection of the neuro-glio-vascular machinery in the adult brainGregory W. Kirschen0Rachel Kéry1Hanxiao Liu2Afrinash Ahamad3Liang Chen4Wendy Akmentin5Ramya Kumar6Joel Levine7Qiaojie Xiong8Shaoyu Ge9Medical Scientist Training ProgramMedical Scientist Training ProgramDepartment of Neurobiology & Behavior, SUNY Stony BrookSchool of Health Technology & Management, Stony Brook UniversityDepartment of Neurobiology & Behavior, SUNY Stony BrookDepartment of Neurobiology & Behavior, SUNY Stony BrookDepartment of Neurobiology & Behavior, SUNY Stony BrookDepartment of Neurobiology & Behavior, SUNY Stony BrookDepartment of Neurobiology & Behavior, SUNY Stony BrookDepartment of Neurobiology & Behavior, SUNY Stony BrookAbstract The adult brain actively controls its metabolic homeostasis via the circulatory system at the blood brain barrier interface. The mechanisms underlying the functional coupling from neuron to vessel remain poorly understood. Here, we established a novel method to genetically isolate the individual components of this coupling machinery using a combination of viral vectors. We first discovered a surprising non-uniformity of the glio-vascular structure in different brain regions. We carried out a viral injection screen and found that intravenous Canine Adenovirus 2 (CAV2) preferentially targeted perivascular astrocytes throughout the adult brain, with sparing of the hippocampal hilus from infection. Using this new intravenous method to target astrocytes, we selectively ablated these cells and observed severe defects in hippocampus-dependent contextual memory and the metabolically regulated process of hippocampal neurogenesis. Combined with AAV9 targeting of neurons and endothelial cells, all components of the neuro-glio-vascular machinery can be simultaneously labeled for genetic manipulation. Together, we demonstrate a novel method, which we term CATNAP (CAV/AAV Targeting of Neurons and Astrocytes Perivascularly), to target and manipulate the neuro-glio-vascular machinery in the adult brain.http://link.springer.com/article/10.1186/s13041-017-0345-4Neurovascular couplingAstrocyteCanine adenovirusAdeno associated virusAdult hippocampal neurogenesisDentate granule cell |
| spellingShingle | Gregory W. Kirschen Rachel Kéry Hanxiao Liu Afrinash Ahamad Liang Chen Wendy Akmentin Ramya Kumar Joel Levine Qiaojie Xiong Shaoyu Ge Genetic dissection of the neuro-glio-vascular machinery in the adult brain Molecular Brain Neurovascular coupling Astrocyte Canine adenovirus Adeno associated virus Adult hippocampal neurogenesis Dentate granule cell |
| title | Genetic dissection of the neuro-glio-vascular machinery in the adult brain |
| title_full | Genetic dissection of the neuro-glio-vascular machinery in the adult brain |
| title_fullStr | Genetic dissection of the neuro-glio-vascular machinery in the adult brain |
| title_full_unstemmed | Genetic dissection of the neuro-glio-vascular machinery in the adult brain |
| title_short | Genetic dissection of the neuro-glio-vascular machinery in the adult brain |
| title_sort | genetic dissection of the neuro glio vascular machinery in the adult brain |
| topic | Neurovascular coupling Astrocyte Canine adenovirus Adeno associated virus Adult hippocampal neurogenesis Dentate granule cell |
| url | http://link.springer.com/article/10.1186/s13041-017-0345-4 |
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