All ETDs from UAB

Advisory Committee Chair

Alecia K Gross

Advisory Committee Members

Lynn E Dobrunz

Mary Anne Garner

Document Type

Thesis

Date of Award

2023

Degree Name by School

Master of Science (MS) Heersink School of Medicine

Abstract

Neuropeptide Y (NPY), a 36-amino acid peptide, has been found to be the most abundant neuropeptide in the central nervous system, and it is widespread across mammalian species. NPY plays a dual role as a neurotransmitter and neuromodulator in the nervous system. NPY functions as a multifaceted neuromodulator through binding NPY receptors (NPYRs). NYP interacts with NPYRs and regulates various activities, such as cell growth, neurogenesis, neuroprotection, mitochondrial behaviors, food intake, anxiety, and addiction formation. In terms of NPY’s neuroprotective potential, NPY inhibits neuronal death signaling, thus preventing apoptosis, and displays anti-inflammatory and anti-oxidative effects. Additionally, it influences metabolism by enhancing glucose utilization in neurons. NPY and NPYRs immunoreactive responses are found in human and mammalian retinas, yet NPY's exact role, and its potential involvement in neurodegenerative diseases in the retina, remain uncertain. Autosomal dominant Retinitis Pigmentosa (adRP), one of the most prevalent retinal degenerative disorders, can be induced by a number of gene mutations, including RhoP23H. In the RhoP23H mouse model, a proline-to-histidine replacement at rhodopsin's 23rd position leads to rhodopsin misfolding and accumulation in the rod photoreceptor, which causes endoplasmic reticulum stress (ER stress) and caspase-dependent and/or-independent pathways of apoptosis, necroptosis, and autophagy. Massive rod photoreceptor loss results in retinal inflammation, cone photoreceptor loss, and eventual blindness. In pathology, the progression of adRP results in night blindness, loss of peripheral visual field (tunnel vision), color insensitivity, and ultimately complete vision loss. In summary, NPY's multifaceted functions encompass neurotransmission, neuromodulation, and potential neuroprotection, offering a possible treatment for retinal degenerative diseases like adRP. Therefore, I hypothesize that the overexpression of NPY can decrease the loss of photoreceptors and delay retinal degeneration in the RhoP23H mouse model.

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