Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


thesis FINAL.pdf (2.2 MB)

ETD Abstract Container

Abstract Header

Analyzing astrocyte reactivity in a mouse model of brain arteriovenous malformation

Butler, Lindsey Mae
http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1683124374591375

Abstract Details

2023, Bachelor of Science (BS), Ohio University, Neuroscience.
Brain arteriovenous malformation (bAVM) is a neurovascular disease in which the connections between arteries and veins become enlarged, abnormal, and prone to rupture. While AVMs are rare, seen in less than one percent of adults, they account for two percent of all hemorrhagic strokes in adults and are the most common cause of hemorrhagic strokes in children. Brain AVMs can also cause headaches, neurological deficits, and even seizures. Despite these serious consequences, treatment options for bAVM remain highly invasive and are not possible for many patients. Understanding the role of other brain cell types in the context of this neurovascular disease could provide alternative treatment options to test. In this thesis, a genetically induced mouse model of AVM was used to better understand the consequences of the disease for the brain. In our model, the gene Rbpj, which encodes a transcription factor and is a downstream target of Notch signaling, was deleted from endothelial cells just after birth (postnatal day (P) 1). While in our mouse model the genetic mutation is induced in endothelial cells, which form blood vessels, other brain cell types, such as pericytes and microglia are also affected. However, it is not known whether astrocytes, another important brain cell type, are affected in our bAVM model. Astrocytes are important in tissue homeostasis of the brain and are closely associated with endothelial cells and capillary blood vessels in the brain. In many neurological disorders, astrocytes change their behavior and may show astrocyte reactivity. Astrocyte reactivity is characterized by changes in shape, increased proliferation, altered gene expression and metabolic function. In our Rbpj-induced mouse model of AVM, I investigated consequences of the disease for astrocytes, hypothesizing that in our model, astrocytes would show characteristics of reactivity and formation of glial scars. When Rbpj was deleted at P1, I found that affected astrocytes showed characteristics of reactivity such as increased GFAP expression in the cerebellum and cortex at P14 and P21, increased proliferation in the cortex and cerebellum at P14, and formation of glial (astrocytic) scars at P14. I also found preliminary evidence of altered gene expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (Pfkf3β), complement factor 3 (C3), glial fibrillary acidic protein (GFAP) and monocarboxylate transporter 1 (MCT1). These results suggest that astrocytes are reactive in our model of bAVM and may have altered metabolism.
Janet Duerr (Advisor)
Corinne Nielsen (Advisor)
55 p.
Biology; Biomedical Research; Cellular Biology; Molecular Biology; Neurobiology; Neurology; Neurosciences
brain; arteriovenous malformation; vascular disease; stroke; mouse model; genetics; astrocytes; astrocyte reactivity; reactive astrocytes; ischemia; vascular malformation; AVM

Recommended Citations

Citations

  • Butler, L. M. (2023). Analyzing astrocyte reactivity in a mouse model of brain arteriovenous malformation [Undergraduate thesis, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1683124374591375

    APA Style (7th edition)

  • Butler, Lindsey. Analyzing astrocyte reactivity in a mouse model of brain arteriovenous malformation. 2023. Ohio University, Undergraduate thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1683124374591375.

    MLA Style (8th edition)

  • Butler, Lindsey. "Analyzing astrocyte reactivity in a mouse model of brain arteriovenous malformation." Undergraduate thesis, Ohio University, 2023. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1683124374591375

    Chicago Manual of Style (17th edition)

ouhonors1683124374591375
28
© 2023, all rights reserved.
This open access ETD is published by Ohio University Honors Tutorial College and OhioLINK.