New Insights into Nerve Regeneration in the Central Nervous System (CNS): Response of Rat Hippocampal Neurons to Chemical and Electrical Cues

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Overview

Title
New Insights into Nerve Regeneration in the Central Nervous System (CNS): Response of Rat Hippocampal Neurons to Chemical and Electrical Cues
Contributors
Kim, Kwang-Min (creator)
Palmore, Tayhas (Director)
Zimmerman, Anita (Reader)
Tripathi, Anubhav (Reader)
Hurt, Robert (Reader)
MacDonald, John (Reader)
Brown University. Biomedical Engineering (sponsor)
Doi
10.7301/Z0VD6WTR
Copyright Date
2013
Abstract
To improve the capability of nerve regeneration following traumatic brain injuries, neurodegenerative diseases, and neurological disorders, it is essential to understand the mechanism that regulates the behaviors of mammalian neurons from the central nervous system (CNS). Toward this end, my Ph.D. dissertation focuses on the responses of neurons to various stimuli that mimic the environment of the CNS. Rat hippocampal neurons were used as a mammalian CNS model. With respect to chemical cues, this study demonstrated apolipoprotein E4 significantly enhanced neuronal adhesion and neurite outgrowth when compared to laminin, which is a conventional neuron culture substrate. With respect to electrical cues, it was shown that hippocampal neurons showed higher resistance to electric field as they have maturated axon and dendrites. These responses of neurons from the CNS are unusual and contradictory to the previous studies using neurons from the mammalian peripheral nervous system (PNS) or other species. To further investigate the role of the integrin receptor in CNS neurons, this dissertation also studied the downstream signaling pathways of integrin (ERK, Akt). This study demonstrated that hippocampal neurons used extracellular matrix (ECM)-integrin interaction for the regulation of extension patterns of neurite (i.e., straight or curly neurite) by activating the ERK pathway instead of the Akt pathway. This suggests that neurons in the CNS may require ECM-integrin interaction in order to enhance the efficiency in extending neurite to form synapses. For analyzing and quantifying neuronal behaviors in response to chemical/electrical stimuli, this study developed a novel image processing method by utilizing morphological functions and the Fast Fourier Transform (FFT) algorithm in MATLAB. This automated method enables us to analyze a series of live neuron images in a batch process and determine the changes of neurite growth before and after stimulations, which saves time and labor when compared to conventional image analysis methods based on cell fixation and immunostaining. The culmination of the works in this dissertation will contribute to the areas of brain research that focuses on the development of therapies for neurological disorder or neurodegenerative disease in the CNS.
Keywords
Nerve regeneration
Hippocampal neuron
Nervous system--Regeneration
Central nervous system
Notes
Thesis (Ph.D. -- Brown University (2013)
Extent
18, 161 p.

Citation

Kim, Kwang-Min, "New Insights into Nerve Regeneration in the Central Nervous System (CNS): Response of Rat Hippocampal Neurons to Chemical and Electrical Cues" (2013). Biomedical Engineering Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.7301/Z0VD6WTR

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