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Vishruti Makani_Dissertation_Final.pdf (2.66 MB)

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Novel Neurotrophic and Neuroprotective Properties of the BBB-permeable Polysaccharide, Midi-GAGR

Makani, Vishruti
http://rave.ohiolink.edu/etdc/view?acc_num=mco1438874064

Abstract Details

2015, Doctor of Philosophy (PhD), University of Toledo, Biomedical Sciences (Neurosciences and Neurological Disorders).
Currently, there is no effective medicine for the treatment of neurodegenerative diseases. Current therapeutic agents, including neurotrophic factors, are limited by several shortcomings such as blood brain barrier (BBB)-impermeability, side effects, and short half-life in the blood. During our search for an alternative that overcomes these shortcomings, we discovered that low acyl gellan gum and its cleavage product, midi-GAGR, have strong neuroprotective and neurotrophic properties. Since low acyl gellan gum has few side effects in humans and is biocompatible and relatively stable in the body, it has been used for food additive and medical application in humans. In our study, low acyl gellan gum and midi-GAGR not only enhanced neuritogenesis in neuron-like N2A cells and mouse primary cortical neurons, but also protected those cells from the oxidative insults of lipid and hydrogen peroxide and amyloid beta 42 peptide (cortical neurons). Low acyl gellan gum and midi-GAGR activated a neuron survival signaling pathway that increased the active form of cAMP response element-binding protein (CREB) in the nuclei of cortical neurons. Moreover, we confirmed the blood brain-permeability of midi-GAGR and its structural intactness in SD rats using a fluorescent tag, ANTS. Furthermore, brain-penetrating midi-GAGR maintained its neurotrophic effect for 24 h when administered intranasally into rats. In a peripheral nerve injury rat model, midi-GAGR encapsulated in peptide nanotubes enhanced neuro-regeneration following infraorbital nerve transection. Taken together, midi-GAGR with brain-permeability and strong neuroprotective and neurotrophic properties has promise as therapeutic agent for the treatment of neurodegenerative diseases.
Joshua Park, PhD (Committee Chair)
Nicolas Chiaia, PhD (Committee Member)
Kenneth Hensley, PhD (Committee Member)
David Giovannucci, PhD (Committee Member)
Richard Mooney, PhD (Committee Member)
John Wall, PhD (Committee Member)
112 p.
Biomedical Research; Neurosciences

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Citations

  • Makani, V. (2015). Novel Neurotrophic and Neuroprotective Properties of the BBB-permeable Polysaccharide, Midi-GAGR [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1438874064

    APA Style (7th edition)

  • Makani, Vishruti. Novel Neurotrophic and Neuroprotective Properties of the BBB-permeable Polysaccharide, Midi-GAGR. 2015. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1438874064.

    MLA Style (8th edition)

  • Makani, Vishruti. "Novel Neurotrophic and Neuroprotective Properties of the BBB-permeable Polysaccharide, Midi-GAGR." Doctoral dissertation, University of Toledo, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=mco1438874064

    Chicago Manual of Style (17th edition)

mco1438874064
477
© 2015, all rights reserved.
This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.